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Glimmers of Hope

Published: Summer 2017

Author: Deanna Csomo McCool

Perched on an orange ball taller than she is, Hope Kern giggles as her therapist tells her to stretch one of her long, thin arms and touch her image in a mirror.

“Come on, Hopey-Hope!” says Christy Bartek, a pediatric speech-language pathologist at the Children’s Therapy Center at Memorial Children’s Hospital in South Bend. “You can do it!”Flashing an impish grin, Hope, 7, reaches one red-polished nail toward the mirror but then bends the other direction and pulls off her pink sandal, tossing it onto the ground instead. She lets out a “yay!” and flops onto her back over the ball, laughing.

The exercises are meant to encourage Hope, who has Shprintzen-Goldberg syndrome (SGS), to engage muscles deep within her torso and hips, Bartek explains. The exercises might prevent Hope’s chest from developing mountains and valleys of unusual deformities, or help Hope develop better breath support. The truth is, Hope’s prognosis remains a mystery, because her disorder is so rare. A “rare disease,” by National Institutes of Health standards, is one that affects fewer than 200,000 people in the United States at any given time. Those diagnosed with SGS? Fewer than 50 in the world.

When a child is diagnosed with a disorder, any information is comforting. But Hope’s family hasn’t had that solace. Complete research has been performed on only about 300 of the 7,000 known diseases in the world, according to Kasturi Haldar, director of Notre Dame’s Boler-Parseghian Center for Rare and Neglected Diseases. SGS’s extreme rarity has kept it off a rare-disease list compiled by the National Organization of Rare Disorders (NORD), a nonprofit organization that provides one of three informational portals about rare diseases. Not until Notre Dame scientists from Boler-Parseghian met Hope and her family two years ago did any researcher have the time and resources to submit a detailed description of SGS to NORD, where it’s now under review.

Hope’s mother, Melissa Kern, contacted the Boler-Parseghian Center after the family moved from Bozeman, Montana, to South Bend in 2015, and after years of surgeries and extensive genetic testing finally proved that Hope, then 4, had SGS.

“It will be a huge, huge help to get this listed on NORD, to spread knowledge of this condition,” says her mother. “Right now, when you get a diagnosis, you get just a little packet that lists possible symptoms, and it’s so limited.”

Seen from behind, Hope looks like a skinny kid with maybe something wrong with her feet. Look at her face, and you’ll notice her wide-spaced, prominent eyes, small lower jaw and tapered, long fingers. Spend a few additional minutes, and you’ll hear that she responds more like a preschooler than a 7-year-old. You’ll also discover her charm. Hope has been welcomed as a jovial guest at the past two Rare Disease Day conferences in Jordan Hall each February. There, despite her disabilities, she skitters and skips between her parents and the poster displays, delighting anyone she meets with her exuberant, toothy smile.

“Hope,” says Joseph Farris, a biological sciences graduate student who is among those at Notre Dame researching SGS for the NORD database, “was very appropriately named.”

On June 4, 2010 — one day before Hope’s due date — Melissa and Tim Kern, along with some of their children, piled into the Bozeman Birth Center. They were eager to welcome Hope into the world, although they knew this baby, Melissa’s fifth, could be born with a disability. Months earlier, their midwife performed an ultrasound because she couldn’t locate Hope’s heartbeat with the standard fetal doppler probe. The ultrasound showed Hope was alive, but her umbilical cord had only one artery instead of two. This anomaly can sometimes indicate a genetic disorder. The midwife also couldn’t see Hope’s left foot, which didn’t appear in future ultrasounds, either.

Born at 8 pounds, 11 ounces, with a tuft of brown hair on her crown, Hope immediately cried like any other baby. Her parents were most delighted that she did, indeed, have two feet. But something about her was . . . off.

“When my midwife handed her to me, she was very floppy, like if you could imagine holding a big hunk of Jello in your arms,” Melissa says. Both she and Tim noticed that Hope was missing a nasal bridge — the raised portion of the nose usually found between the eyes. Her eyes were widely spaced and turned downward.

“My midwife kept saying I had a ‘very special little girl,’ and I was thinking she had Down syndrome,” says Melissa.

But the post-birth experience felt typical, she says, until Hope was moved out of the birthing center to a hospital and, later, whisked 200 miles away by helicopter to the Neonatal Intensive Care Unit at Community Medical Center in Missoula, not because of sudden changes in her status but because doctors couldn’t pinpoint her disorder.

“They started doing tests and wouldn’t let us touch her, and put her in a big bubble with monitors everywhere, and she really started going downhill after that,” Melissa says. “We were only allowed to touch her through the bubble, just like on her hand. It was very traumatic.”

Doctors ruled out Down syndrome. They considered several disorders during Hope’s first year, which included five surgeries (three for hernias) and weekly weight checks, because Hope’s weight fell sharply under average weight-gain curves. Tim rigged a gravity-feeding contraption from a microphone stand and a broken teapot handle so Melissa didn’t have to hold a bag of pumped breast milk for the 30 minutes it took Hope, who struggled to nurse or drink because of her underdeveloped lower jaw and high, wide palate, to finish a bottle.

By the end of Hope’s first year, a medical professional told the Kerns that Hope had a connective tissue disorder related to Marfan syndrome, “and she was naturally going to be thin,” Melissa says, lamenting that Hope had undergone an operation to place a gastronomy tube in her abdomen to deliver nutrients to her stomach — a surgery the Kerns now feel was unnecessary. The news, however, meant Hope was a step closer to being diagnosed.

Connective tissues are the glue that holds the body together. Cartilage, for instance. Even bone. Or the dura, a membrane under the skull that surrounds the brain. Faulty connective tissues create a cascade of problems throughout many of the body’s systems. In addition to skeletal abnormalities, those with Marfan syndrome and related disorders can suffer a fatal dilation of the aorta, the body’s largest artery.

Those life-threatening aortic aneurysms were what drove Dr. Hal Dietz, after four years as a pediatrician, into research in 1991. Now the director of the William S. Smilow Center for Marfan Syndrome Research at the Johns Hopkins University School of Medicine, Dietz was frustrated that he couldn’t cure children whose aortas were enlarged as part of their disease. By 2005, Dietz and researcher Dr. Bart Loeys described Loeys-Dietz syndrome, a Marfan-related disorder that Hope’s clinicians settled on after determining her aorta was dilated by age 2½. By 2008, Dietz and his colleagues identified a drug, losartan, that vastly slowed dilations — from about 3.5 millimeters per year to a half a millimeter.

After Hope’s Loeys-Dietz diagnosis, Melissa began combing a Facebook page dedicated to families of children with that disorder. Yet something still didn’t quite fit. Hope also has a moderate developmental disability, which wasn’t a symptom shared by Loeys-Dietz patients. Sensing the diagnosis was incorrect, Melissa reached out to Dietz, emailing him photos and a description of Hope’s symptoms.

Shprintzen-Goldberg syndrome was coined in 1982, but it wasn’t until 2012 that Dietz’s lab, simultaneously with another laboratory in France, homed in on the gene that causes the disorder. Loeys-Dietz syndrome and SGS have overlapping symptoms, including craniosynostosis, the premature fusion of the skull bones, which neurosurgeons corrected for Hope during a life-threatening surgery in 2015. SGS patients are less likely to have aortic malformations than patients with Loeys-Dietz, but when they do, the problem can be more severe. SGS patients also exhibit hernias, scoliosis, joint hypermobility and developmental delays.

Melissa’s email wasn’t an anomaly for Dietz. With the dearth of information about SGS, Dietz fields 40 to 50 calls or emails each week from patients or clinicians about that and other related syndromes.

“It is by the far the most rare of the connective tissue disorders,” Dietz says. “But I stress to people that knowledge is power, knowledge is hope, and I think this is a new beginning for patients, since identifying the gene.”

Genetic testing is expensive, and Hope’s medical disability insurance will pay for only three genes to test each year. Dietz, who wasn’t treating Hope, suggested to her doctors the exact genes to check that would determine whether Hope had SGS.

The results came back positive.

“To finally have a name attached with the disorder is viewed as a great victory and a first opportunity to find answers,” Dietz acknowledges.

Still, says Melissa, “The hard part has been finding information. There’s literally only scholarly papers out there.”

Those, plus Dietz and a Facebook page connecting a few families who have either received a clinical diagnosis or suspect their child has SGS. The information shared there proved life-saving for Hope. Another mother recommended to Melissa that a doctor check Hope’s upper two cervical vertebrae, to determine if they were being crushed by Hope’s skull. The doctor evaluated the two vertebrae, C1 and C2, and immediately scheduled Hope for surgery. She underwent a cranial-cervical fusion where one of her ribs was used to stabilize her neck.

“The literature doesn’t say to have this checked; it just says they can have a C1/C2 abnormality,” Melissa says, pointing to a paper containing a list of symptoms and noting that Hope could have died or become paralyzed. “You don’t even know how serious this can be.”

And this is where the work from Notre Dame’s Boler-Parseghian Center and NORD will bridge the information gap. Haldar, Farris and Barbara Calhoun, the center’s outreach coordinator, completed the paperwork in April to submit to the NORD database. This portal of information on rare diseases is neither too technical nor too simple to be useful to patients. Haldar and Dietz tout it as the leading resource for the diseases it lists.

“Perhaps more importantly, it can provide a sense of community for patients and families, patient advocacy groups, clinicians and scientists with an investment in a rare disorder,” says Dietz, who will complete the final review of the Boler-Parseghian Center’s description before it’s published with NORD.

Hope has undergone 13 surgeries during her seven years. Tim and Melissa say they hope their daughter, whose aorta has shown little dilation since she started losartan last year, will have a surgery-free year. A surgery-free year isn’t only good for her (even though she appears to bounce back quickly from even the most nail-biting procedures, photographed with smiles the next day), but also the family budget. Medical bills are covered by Hope’s disability insurance, but other necessities — from travel, to special bicycles, to food, to special socks — are not. The family must purchase those items on Tim’s salary as a minister with Chi Alpha Campus Ministries or through the generous help of friends, family and service organizations.

“We just have to be creative with what are truly needs and wants with the whole family,” Melissa says. “It’s a juggling act of balance and perspective with a whole lot of faith keeping it together.”

Meanwhile, other therapies continue. In addition to monthly visits with her pediatrician, Hope attends weekly speech therapy with Bartek and twice-weekly appointments at the Judd Leighton Speech and Language Clinic at Saint Mary’s College. At a recent appointment there, Hope played with baby dolls and pretended to cook plastic watermelons before pressing her face against the two-way mirror to smile at her dad, who she knew was watching.

The prolonged medical journey has been unyielding, Tim acknowledges. Still, Melissa tells anyone who asks, “Our family is bubble-wrapped in grace.”

They’re ready to tackle any future issues that arise and welcome the additional resources available once SGS is added to the NORD database.

“Just living close to Notre Dame has been a blessing, because they’re so passionate about rare diseases,” Melissa says. “I don’t know that we could get this close to getting Shprintzen-Goldberg on a national registry without it. It will be such a big help to parents.”

Deanna Csomo McCool is assistant director of marketing communications in Notre Dame’s College of Science and an online graduate student in science writing at Johns Hopkins. Email her at or find her on Twitter at deanna_mccool.

The Notre Dame Chapter of Uplifting Athletes will hold its Annual Community Bowling Event on Sunday, June 25th in Mishawaka, Indiana.

This will be the fourth consecutive year the Notre Dame Chapter holds this event to support its mission of using college football as a platform to inspire the rare disease community with hope through the power of sport.

The proceeds from the Notre Dame Chapter Community Bowling Event support Uplifting Athletes and its commitment to life skills development, patient focused programs and rare disease research.

Click the link below to donate or to purchase tickets.


Xin Lu wins 2017 Indiana CTSI Young Investigator Award

Dr. Xin Lu, the John M. and Mary Jo Boler Assistant Professor of Biological Sciences, in the Boler-Parseghian Center for Rare and Neglected Diseases, has been awarded a Young Investigator Award from the Indiana Clinical and Translational Sciences Institute (CTSI).

Dr. Lu has a broad research program that seeks to understand and target the tumor microenvironment, a forefront basic and translational cancer research in the present day. In this grant proposal Dr. Lu seeks to address a problem that broadly affects difficult-to-treat cancers. Many drugs that can kill cancers are toxic but if they can be selectively delivered to the cancerous cell and released inside of them, then they will more precisely kill the tumor and harmfulness to healthy tissue will be reduced. Dr. Lu has proposed a strategy of coupling drugs to antibodies that can recognize targets on prostate cancer cells and test them in a mouse model that mimics the human cancer mutations, an area in which he is a leading expert.

The title of his proposal is "Novel Antibody-Drug Conjugates for Personalized Therapy of Lethal Prostate Cancer". His findings are expected to have implications for treatment of a broad range of cancers including several rare cancers.

Congratulations to Dr. Lu for this richly deserved award!      

Kasturi Haldar wins 2017 Ganey Award for community-based research

By: JP Shortall

April 13, 2017

Professor Kasturi Haldar has received the 2017 Rodney F. Ganey, Ph.D., Community-Based Research Award for a project that has helped improve rare disease recognition and treatment in northern Indiana. The award is a $5,000 prize presented annually to a regular faculty member at the University of Notre Dame who has completed at least one research project that addresses a need within South Bend or the surrounding area. Haldar is a molecular cell biologist and the Rev. Julius Nieuwland Professor of Biological Sciences and Parsons-Quinn director of the Boler-Parseghian Center for Rare and Neglected Diseases at the University of Notre Dame.

There are currently about 7,000 recognized rare diseases in the United States, and most medical clinicians will encounter only a small fraction of them even after years of practice in the clinic. So what does a clinician do when a patient with a rare disease appears in her clinic? She might reach out to a rare disease specialist or genetic center for support if she has easy access to either of those. They could provide her with the clinical spectrum of related rare diseases to review and compare with her patient’s symptomatology. But clinicians have demanding schedules and often no ready access to this kind of external support.

In northern Indiana, clinicians have long had to seek support for rare disease identification and diagnosis from Riley Children’s Health or Indiana University Health in Indianapolis. Because those facilities are distant and often busy, accessing them can be time-consuming, and the key to treatment of any disease is accurate and timely diagnosis and management.

So in 2015-16, a team led by Dr. Kasturi Haldar, director of the Boler-Parseghian Center for Rare and Neglected Diseases (CRND) at the University of Notre Dame, applied for and received a Ganey Collaborative Community-Based Research Seed Grant for a project to improve rare disease management and treatment locally. The grant helped her and her team partner with advanced pre-med students, local pediatricians, and families of rare disease patients, as well the National Organization of Rare Diseases, the Michiana Health Information Network, and CRND to create a knowledge base and analytic framework for rare disease recognition right here in northern Indiana.

Using the combined resources of this partnership, Haldar and her team have developed a program that trains upper level pre-med students to evaluate rare disease patient medical records and help produce natural histories of disease. They then provide a local pediatric clinic with tools to strengthen the clinical context to manage and treat children with rare genetic disorders, empowering them with the most current data. This decreases the time to proper diagnostic understanding and the establishment of a clear course of treatment. The project also empowers patient families by providing clinicians with up to date information on centers of excellence and other resources that they share with patients. At the Annual Notre Dame Rare Disease Day Conference every February, students also partner with patients to present poster and community-based patient talks.

The project has clearly impacted pediatric health care for rare disease cases in northern Indiana, but its impact has also gone beyond the region. In 2015-16, Haldar’s team produced a case report of an unusual occurrence of neurofibromatosis (NF1), a rare genetic neurologic disorder. The report, “Aggressive Tibial Pseudarthrosis as Primary Symptom in Infant with Neurofibromatosis, which suggests need for modification of federal guidelines for NF1 diagnosis,” has now been published by Cold Spring Harbor Laboratory’s bioRxiv, where it will be available for review by the scientific community.

Contact: JP Shortall,


RareND Team builds ZEBRA, award winning app in Notre Dame App Challenge and goal for Precision Medicine!

"When you hear hoof beats, think of horses not zebras" was how Dr. Theodore Woodward, at the University of Maryland, counseled medical interns in 1940s. But the best of modern medicine seeks the zebra in all of us. This is the goal of ‘Precision Medicine’, where we leave behind the ‘average’ patient and instead focus on individual differences in genes and other molecular determinants, as well as the impact of environment and life style to understand a patient’s disease and how to treat it.

Precision Medicine is a revolution in health care. It is based on the rare disease model. Precision medicine seeks the zebra in that it looks for what makes you unique. In a rare disease, every patient unique. This is why the individual patient is at the center of rare disease treatment, empowered to collaborate to fund research and share their complex biological and health data in a network of doctors, patients and advocates, in search of transformative outcomes.

Congratulations to Anna Volk, Will Langbo, Kim Trouch, and Katherine Inskeep in developing an important advocacy tool for patient-centered medicine and winning 3rd place in the first ND App Challenge!

The ND App Challenge was sponsored by the Office of the Executive Vice President, and organized by SAP, Innovation Park at Notre Dame and the Office of Information Technologies. In the challenge, over 70 teams from across Notre Dame created mobile apps responsive to President Rev. John I. Jenkins, C.S.C. call to action “I now ask all of you to join me in supporting these collaborative efforts to advance our vision of Notre Dame as a powerful force to heal, unify and enlighten our world.”


Rare Disease Day 2017


Video archive


CRND Newsletter Vol. 5, Dec. 2016

NKH Focus Group 2016

Thanks to the Sarbs and Fitzpatricks for speaking with the students on Friday about Notre Dame and NKH research. Students have a better understanding of the affect that NKH disease has on patients and families. They worked on ways to raise awareness through social media and developed a facebook page to advertise this event. Good Job ND students!
Thank you to Pat and Lynda for sharing their story of the Sarb's long standing history with Notre Dame starting with Father Sorin and now working with Dr. Haldar and CRND staff on NKH research.
Mary and John Fitzpatrick were gracious to share their family experiences with caring for a child with NKH and how they are raising funds for research through "Fiona and Friends" through the sale of wristbands $3 each and all proceeds go to this fund for NKH Research.

For more details on this event, please visit:

NKH Focus Group




Boler-Parseghian Center for Rare and Neglected Diseases NOTRE DAME DAY Campaign Interview
April 25th, 2016:

View campaign details at:





Notre Dame Rare Disease Fight Song

Rare Disease Fight Song from Rareandneglected on Vimeo.


Spring 2016 News

View the entire article at:


Fall 2015 CTSS Seminar Guest Lecture


Friday, December 4, 2015

DeBartolo Hall room 208 11 am.

Wyndham Lathem, Ph.D.

Associate Professor, Dept. of Microbiology-Immunology

Northwestern University Feinberg School of Medicine

"How a Single Gene Changed History: Retracing the Evolution of Pneumonic Plague."

Dr. Wyndham Lathem

Seminar on December 4th, 2015

“The adaptation of bacterial pathogens to new hosts and specific microenvironments within the body typically occurs via the combined gain and/or loss of genetic elements during the evolution of the species. Yersinia pestis, responsible for the devastating respiratory infection known as pneumonic plague, is a recently evolved clone of the gastrointestinal pathogen
Y. pseudotuberculosis
, and represents one of the best models to examine the emergence of new virulence traits and mechanisms of disease. In this presentation, I will discuss our recent studies to identify the specific genetic changes that endowed Y. pestis with the ability to infect the lungs as it evolved from Y. pseudotuberculosis over the past 5,00010,000 years. In addition, I will describe how the acquisition of a single gene encoding the outer membrane Pla protease enabled Y. pestis to coopt host fibrinolysis factor plasminogen to cause pneumonic plague, and the surprising role of plasminogen as a “danger signal” to trigger the immune response during infection.”


Friday, November 13, 2015

DeBartolo Hall room 319 2:15 pm.

Johan L. Van Hove, M.D., Ph.D.

Professor of Pediatrics, Dept. of Pediatrics

University of Colorado School of Medicine,
Anschutz Medical Campus

"What indicates clinical outcome in nonketotic hyperglycinemia?"

Dr. Johan Van Hove

Seminar on November 13th, 2015

“Nonketotic hyperglycinemia is a rare genetic neruometabolic disorder that is caused by deficient activity of the glycine cleavage enzyme. Most children present in the neonatal period with hypotonia, transient apnea, coma and seizures. They go on to develop spasticity, therapy resistant seizures, and complete lack of neurological development. Yet, there are children with this condition, that make substantial developmental progress, have no or easily treatable seizures. In this presentation we will review what distinguishes these different outcomes and how this information can be used for development of treatment.”


Friday, November 6, 2015

DeBartolo Hall room 208 11:00 am.

Iddo Friedberg, Ph.D.

Associate Professor in Computational Biology,
Dept. of Veterinary Microbiology and Preventive Medicine

College of Veterinary Science,
Iowa State University

"Understanding Biological Function in Times of High Throughput and Low Output."

Dr. Iddo Friedberg

Seminar on November 6th, 2015

“High throughput biological assays are providing us with a wealth of data. However, sifting through these data to extract meaningful biological information is the challenge of early 21st Century biomedicine. The gap between the data that we have, and the useful information we extract from it is growing exponentially. I will discuss two aspects of this problem.

The first problem is that of assigning a function to a gene or a gene product. In many cases, homology searches do not yield an accurate answer, or any answer at all. For that reason, computational biologists have developed methods that consider many other attributes in the sequence's data and metadata. At the same time, it is hard to decipher which methods perform better, what “better” is, and the suitability of methods to given task: that is the second problem. To help solve this problem, we formed a consortium of the Critical Assessment of Function Annotations, a community effort to improve prediction of function from protein sequences. I will discuss the CAFA effort, and how it serves the biomedical community at large by providing an updated picture of how well we can understand biology from sequence data.”


Friday, October 30, 2015

DeBartolo Hall room 208 11:00 am.


Zachary T. Schafer, Ph.D.

Coleman Foundation Collegiate Chair of Cancer Biology,
Associate Professor, Dept. of Biological Sciences

University of Notre Dame


"Tumor Cell Survival During Detachment from the Extracellular Matrix: The Achilles Heel of Cancer Metastasis?"

Dr. Zachary T. Schafer

Seminar on October 30th, 2015

“Metastasis, the spread of cancer from the site of the primary tumor to distant locations in the body, is responsible for in excess of 90% of cancer deaths, yet the molecular mechanisms governing this extraordinarily complicated process remain poorly understood. It has become clear that an important barrier to metastasis is the induction of anoikis, a cell death process that is induced when epithelial cells lose attachment to the extracellular matrix (ECM). The overarching goal of my laboratory's work is to examine and characterize the biological mechanisms that permit cancer cell survival in the absence of ECM attachment. It is our hope that a better understanding of these mechanisms will reveal novel chemotherapeutic targets or approaches that may serve to compromise the survival of ECM-detached cancer cells and thus prevent tumors from successfully metastasizing. 

There are currently 4 distinct, major research projects ongoing in the lab that are all aimed at achieving the aforementioned goal:

    1. The role of ROS in the survival of ECM-detached cancer cells
    2. Carcinoma-associated fibroblast-mediated inhibition of anoikis in breast cancer cells.
    3. Tumor cell survival in inflammatory breast cancer.
    4. Oncogenic signaling involved in anoikis regulation.

During this seminar, I will focus on our most recent studies that have unveiled novel mechanisms utilized by ECM-detached cancer cells to survive and will discuss how we might take advantage of this knowledge to eliminated metastatic cancer cells.”



Friday, October 16, 2015

DeBartolo Hall room 319 2:00 pm.


Dimitri Krainc, M.D., Ph.D.

Chair, Department of Neurology Director, Center for Rare Neurological Diseases,
Aaron Montgomery Ward Professor

Northwestern University Feinberg School of Medicine

"Gaucher's and Parkinson's disease: how are they linked?"




Friday, October 2, 2015

DeBartolo Hall room 208 11:00 am.


Daniel Goldberg, M.D., Ph.D.

Professor of Internal Medicine, Infectious Diseases, and Molecular Microbiology

Howard Hughes Medical Institute

"Manipulation of host vascular biology by the malaria parasite Plasmodium falciparum."


Dr. Daniel Goldberg

Visit on October 2nd, 2015

“Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, vasoconstriction and vascular leakage. P. falciparum produces and exports several hundred proteins into its host erythrocyte. We are interested in establishing the function of these effectors.

One such protein is histidine-rich protein II (HRPII). Plasma HRPII accumulates in the blood of patients with falciparum malaria and is a diagnostic and prognostic marker. Using a human cerebral microvascular endothelial blood-brain barrier (BBB) model, we have found that HRPII activates the inflammasome, resulting in decreased integrity of tight junctions and increased permeability. Intravenous administration of HRPII induces vascular leakage in the brains of mice, tight junction protein redistribution and increased early mortality from P. berghei experimental cerebral malaria. We propose that HRPII is a virulence factor that contributes to cerebral malaria by compromising BBB integrity.

Erythrocytes are storage reservoirs for epoxide-containing lipid signaling molecules, including epoxyeicosatrienoic acids (EETs) and epoxy​octadecenoic acids (EpOMEs).  EETs/EpOMEs function as vasodilators and anti-inflammatory modulators in the blood stream. These bioactive epoxides are hydrolyzed by epoxide hydrolases, converting them into inactive diols. We have identified and characterized two epoxide hydrolases (EH) of Plasmodium falciparum, PfEH1 and PfEH2. Both proteins are exported to the periphery of infected erythrocytes and both convert several EET regioisomers to the corresponding diols.  Manipulation of PfEH1 or PfEH2 levels in parasites results in a significant alteration in the epoxy fatty acid content of infected erythrocyte phospholipids. P. berghei has no predicted exported EHs, but chemical inhibition of the host EH enzyme reduced the percentage of mice that developed severe, cerebral malaria, without reducing parasitemia. We hypothesize that the parasite disruption of EETs/EpOMEs leads to perturbed vascular function. Both the EHs and HRPII promote favorable conditions for binding and sequestration of infected erythrocytes to the microvascular endothelium.”




Friday, September 18, 2015

DeBartolo Hall room 208 11:00 am.


Shaun Lee Ph.D.

Assistant Professor, Dept. of Biological Sciences

University of Notre Dame

Shaun Lee

"Fighting Microbes: Discovery and Use of Peptide- Based Bacteriocins"

Dr. Shaun Lee

Visit on September 18th, 2015

"Small peptides provide an untapped source of structural diversity much needed in pushing the frontiers of discovering new small molecule therapeutics. Peptides that are produced ribosomally by bacterial organisms are broadly known as bacteriocins. These bacteriocins comprise a large class of peptide families that have been shown to be effective as antibiotics, food preservatives, anti-infectives and anti-cancer therapeutics. With rapid advances in genomics and natural product discovery, we are currently seeing a tremendous 'explosion' in the identification and use of these ribosomally produced bacterial peptides for drug development.

One major family of peptide bacteriocins produced by bacteria are the TOMMs (thiazaole-oxazole containing modified microcins), exemplified by the hemolytic toxin known as Streptolysin S (SLS). SLS is produced by the significant human pathogen Group A Streptococcus,  a major cause of rheumatic diseases as well as invasive outcomes such as necrotizing fasciitis. Although it has been widely held that SLS exerts its lytic activity through membrane disruption, its exact mode of action has remained unknown.  We have recently demonstrated using high-resolution live cell imaging, that SLS induces a dramatic osmotic change in Red Blood Cells (RBC), leading to cell lysis. This osmotic change was characterized by SLS-mediated disruption of the major erythrocyte anion exchange protein, Band 3. Chemical inhibition of Band 3 function significantly reduced the hemolytic activity of SLS, and dramatically reduced pathology in an in vivo skin model of GAS infection.  In addition to its well-recognized role as a cytolysin, recent evidence has indicated that SLS may influence host cell signal transduction at sub-lytic concentrations during the infection process.  We identified key SLS-dependent host responses, including the initiation of specific cell death and inflammatory cascades such as Mitogen Activated Protein Kinase (MAPK) and Nuclear Factor kappa B (NFκB) signaling. 

In addition to our research efforts on the mechanims of SLS function, my research program at the University of Notre Dame continues to study mechanisms of bacteriocin production and function in diverse microorganisms, along with their roles in influencing microbial dynamics. We have identified biochemical strategies that allow for the production of diverse artificial bacteriocin libraries in high yield. These strategies will greatly expand the chemical repertoire of existing compounds, and open significant avenues into new drug research."



Friday, September 4, 2015

DeBartolo Hall room 319 2-3pm.


John F. Crowley, Chariman and CEO

Amicus Therapeutics Inc.

Hung Do, PhD, Chief Scientific Officer

Amicus Therapeutics Inc.

"When Drug Research is Personal: A Brief History of the journey toward a medicine for Pompe Disease".

John Crowley and Dr. Hung Do

Visit on September 4th, 2015

On Friday Sept 4th 2015, CRND held this season’s first Rare Disease Clinical Translational Seminar presented by John Crowley (J.D. Chairman and CEO) and Hung Do (Ph.D., Chief Scientific Officer) of Amicus Therapeutics. Amicus focuses on discovery and development of treatments for rare genetic disorders with particular interest in lysosomal storage diseases (LSD).  The research is personal because after two of his children were diagnosed with Pompe, a severe muscular glycogen storage disorder, John Crowley led a biotechnology company (Novazyme) that set on course the development of an enzyme replacement therapy (ERT) for Pompe, to treat his children’s disease.

Lysosomal storage diseases are ~50 rare inherited disorders that result from defective function of lysosomes, cellular compartments that break down large molecules (like proteins, lipids and complex sugars). When mutation renders a defect in a lysosomal protein, lysosomal degradation slows down/ becomes blocked, leading to excess accumulation of large molecules and eventually to cell and tissue malfunction.  In Pompe, the defect is in a lysosomal (protein) enzyme alpha-glucosidase (GAA), needed to break down glycogen and convert it into glucose.   A way to treat Pompe is to deliver ‘pre-made’ GAA into the blood stream from where it can be delivered to cells and into lysosomes, to rescue the defect.  But proper delivery is a complex multistep process, during which even the pre-made GAA enzyme can lose substantial structure and function and therefore potency.  Therefore Amicus Therapeutics has designed small molecule ‘chaperones’ that help the pre-made GAA enzyme better retain its structure and function.  The chaperones can also help to rescue endogenous mutant GAA protein in the patient.  A clinical trial for chaperones combined with ERT is underway for Pompe. 

We reflected on a remarkable dual partnership, with John Crowley providing the historical context and his family’s story and Dr. Hung Do presenting the recent science data on the effect of combining chaperones with enzyme replacement therapy in preclinical models. Dr. Do received his Ph.D. (in Biochemistry and Genetics) from Texas A&M University.  He did post-doctoral training at Emory University. He is an expert and industry leader on both chaperone therapy and ERT.  John Crowley received his JD from University of Notre Dame and MBA from Harvard University. He has received numerous accolades and recognition for his outstanding business leadership, social service and philanthropy.

To his family’s inspiring and well chronicled story, another extraordinary chapter was added this fall, when his daughter enrolled as a freshman, as the first student with Pompe Disease at Notre Dame.  




Thanks to all who joined us for the CRND end of semester celebration on May 26th!

We enjoyed a fun time with food, family and friends in celebrating another great semester.

During the celebration, we recognized CRND faculty who received promotion and tenure.

We also recognized those who participated in the first CRND research competition and Dr. Alassane Mbengue and Dr. Cassandra Buchheit the winners of the CRND award for Excellence in Rare and Neglected Disease Research.

Dr. Alassane Mbengue and Dr. Kasturi Haldar

Dr. Zack Schafer recieved on behalf of Dr. Cassandra Buchheit and Dr. Kasturi Haldar

To see more pictures from the awards banquet please see our event photo gallery


2015 CRND award for excellence in rare and neglected diseases winners

The winners of the inaugural CRND award for excellence in rare and neglected diseases are as follow:

Dr. Cassandra Buchheit (Schafer lab)

Dr. Buchheit is the graduate student winner, for her outstanding work on a rare cancer known as inflammatory breast cancer.  See Cassie’s recent published paper on ‘Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration’ published in the journal Cell Death and Differentiation in December 2014.  The work was supported by the Elsa U. Pardee Foundation, the Coleman Foundation and the American Cancer Society, as well as graduate fellowship support to Cassie from CRND.

Dr. Alassane Mbengue (Haldar lab)

Dr. Mbengue is the postdoctoral scholar winner for his outstanding work in drug resistance in malaria.  See Alassane’s recent published study on , “A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria,” published in Nature in the journal April 2015.  The work was supported by the National Institutes of Health and Notre Dame International.

The CRND award for excellence in rare and neglected diseases will be made annually.  To be considered for the award, applicants must be nominated by their advisor and provide additional information as required by the guidelines. Each application is then evaluated by independent reviewers with appropriate expertise and scored in four categories pertinent to research training and productivity.

We were excited that in the first year, we had a very strong pool of applicants.  We thank all the participants for their excellent contributions  

The winners will receive a $1,000 cash prize and a plaque recognizing their outstanding achievements in rare and neglected diseases research.

Congratulations to Cassandra and Alassane!




On your promotion to Associate Professor with Tenure...

Patty Champion

Shaun Lee

Zach Schafer

Basar Bilgicer


On your promotion to Research Associate Professor...

Matt Champion


RareND student club raising awareness with “Five Guys” fundraiser

On Tuesday April 28, 2015, the Notre Dame RareND club gathered for dinner at Five Guys restaurant at Eddy St. Commons. As part of this organized activity, the restaurant donated a percentage of its profits from that day to the club. Since it gained its club status by the SAO, RareND has been engaged in a number of activities on and off campus to raise awareness among ND students and in the community at large for rare diseases. Following a strong showing for Notre Dame day, the Five Guys fundraiser will help support the club activities in spreading the word about rare diseases. To learn more about upcoming events, check out the RareND Facebook page.



CRND scientist discusses challenges for developing new malaria therapies on World Malaria Day

Dr. Kasturi Haldar co-authors a commentary in PLOS 'Speaking of Medicine' community blog

"Drugs for Malaria: Need to Overcome Resistance to Artemisinins and Eliminate All Stages of Parasites in a Wide Range of Transmission and Disease Settings

By Kasturi Haldar and Margaret Phillips


Targeting the parasite: a malarial sporozoite in an infected epithelial cell. Image credit: Frevert et al.

The second decade of the 21st century has been infused with optimism for malaria eradication. Although deadlines have been breached, it appears that the cumulative and long haul fight against malaria is yielding impactful results: reduction of malaria deaths from a staggering 1.2 million to ~ 600,000 from 2000 to 2013 provides a realistic context for elimination and eradication agendas. But the path forward is not just details. Major discoveries in basic, translational and capacity building research supported by commensurate funding are urgently needed to navigate challenges posed by dynamic and heterogeneous disease frontiers."

Read More


CRND Researchers identify molecular mechanism responsible for making malaria parasites drug-resistant

By: Stephanie Healey

University of Notre Dame researchers led an international team to identify a molecular mechanism responsible for making malaria parasites resistant to artemisinins, the leading class of antimalarial drugs.

Red blood cells infected with human malaria parasite Plasmodium falciparum at the 'ring' stage, either sensitive or resistant to artemisinins.  Within parasites  (orange with blue nucleus) that are sensitive, the target of artemisinins phosphatidylinositol-3-kinase (PI3K; green triangles) is bound to and regulated by Kelch13 (disk, multicolored), while in resistant parasites this regulation is disrupted. 

According to the World Health Organization’s 2014 World Malaria Report, there are an estimated 198 million cases of malaria worldwide with 3.3 billion people at risk for contracting the infection. Although the impact of malaria is still significant, the statistics reflect a considerable reduction in the global malaria burden. Since 2010, disease transmission has been reduced by 30 percent and mortality due to malaria has decreased by almost half.

Artemisinins are powerful drugs that have the most rapid action of all current drugs against Plasmodium falciparum, the parasite species that causes the most dangerous form of malaria. Artemisinin combination therapies (ACTs) are now standard treatment worldwide for P. falciparum malaria. Unfortunately, resistance to artemisinin has been detected in five countries across Southeast Asia. Along the Cambodia-Thailand border, P. falciparum is now resistant to most available antimalarial drugs. Artemisinin resistance poses a serious global threat to malaria control and elimination.

“There are two phases of blood stage malaria infection. In the first phase, the ‘ring’ parasite stage circulates in the bloodstream, and in the second phase, the ‘mature’ parasite stage sequesters in the tissues of the body,” explained Kasturi Haldar, the Rev. Julius A. Nieuwland Professor of Biological Sciences and the James C. Parsons and Carrie Ann Quinn Director of the Boler-Parseghian Center for Rare and Neglected Diseases. “Artemisinins are highly effective in treating malaria quickly because they target the first ring stage. When patients take the medication, their fevers reduce quickly, and the parasite is eliminated rapidly.”

Although artemisinins have been widely used and investigated, no one fully understood how they worked or why clinical resistance has emerged. Laboratory studies showed that artemisinins were always active against the mature parasite stages that sequester in tissues, but clinicians were observing resistant infections from patients who were still in early stage of infections. In addition, previous genome wide association studies of P. falciparum identified genes associated with artemisinin resistance, but it was unknown how the genes worked. This Notre Dame-led study identified both the target of artemisinins in the clinically affected ring stages and how a gene named PfKelch13, a dominant marker used to track the parasite’s resistance, causes artemisinin resistance.

“We observed that levels of a lipid called phosphatidylinositol-3-phosphate (PI3P) were higher in artemisinin-resistant P. falciparum than artemisinin-sensitive strains,” said Alassane Mbengue, a postdoctoral associate in biological sciences and co-first author on the study. “This lipid is produced by an enzyme called PfPI3K. We found that artemisinins block this kinase from producing PI3P lipids.”

“We also discovered that the amount of the kinase present in the parasite is controlled by the gene PfKelch13,” Mbengue said. “Mutation in the gene increases the kinase levels, which in turn increases PI3P lipid levels. The higher the level of PI3P lipids present in the parasite, the greater the level of artemisinin resistance. We also studied the lipid levels in parasites without the gene mutation and observed that when PI3P lipid levels were increased artificially, the parasites still became proportionately resistant.”

“Our results are especially significant because we studied clinical parasites from Cambodia, where artemisinin resistance is highly prevalent,” explained Souvik Bhattacharjee, research assistant professor of biological sciences and co-first author of the paper. “We collaborated with researchers and clinicians in Asia, Europe and the U.S. This was true cooperation over several years at both the international and the local levels.”

Other Notre Dame collaborators on the study included Rob Stahelin at Indiana University School of Medicine-South Bend, Olaf Wiest in the Department of Chemistry and Biochemistry, theComputer Assisted Molecular Design Core, Shahir Rizk in the Department of Biological Sciences, and the Genomics and Bioinformatics Core.

When asked about the next steps for this research, Bhattacharjee said, “There are presently two options for overcoming artemisinin resistance. Working with our colleagues at Notre Dame, Eli Lilly & Co. and the Medicines for Malaria Venture, we need to find drugs that kill the parasite by blocking the function of the kinase from making the PI3P lipid or disrupting the production of the kinase itself.”

The study, “A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria,” was published online in Nature on Wednesday (April 15). This work was supported by the National Institutes of Health, the Parsons-Quinn Endowment and Notre Dame International.

Contact: Kasturi Haldar, 574-631-1474,


College of Science Joint Annual Meeting (COS-JAM)

The ninth annual College of Science Joint Annual Meeting (COS-JAM) well be held in the Jordan Hall of Science on Friday, May 1, 2015, as part of the eighth Undergraduate Scholars Conference. The intent of COS-JAM is to highlight the achievements of undergraduate students conducting research in all disciplines of science.



Two recent papers shed light on how breast cancer cells avoid cell death

Two new papers from the lab of CRND Professor Zach Schafer, Coleman Assistant Professor of Cancer Biology at the University of Notre Dame, offer insights into how breast cancer cells avoid anoikis, which is cell death induced by detachment from the extracellular matrix (ECM).

Schafer Lab

To see full article by William Gilroy click here...




Thank You



CRND Celebrates Rare Disease Day


By: Jayme Russell

The Boler-Parseghian Center for Rare and Neglected Diseases recently held a two-day Rare Disease Symposium (February 13-14) and invited researchers, patients, families, physicians, and advocacy groups to speak about their personal experiences with rare diseases. The symposium anticipated Rare Disease Day, recognized worldwide on the last day of February.

Organized by Barbara Calhoun, nurse practitioner and outreach coordinator for the Boler-Parseghian Center, the event featured research presentations as well as discussion panels focused on patient experiences. Because there are roughly 7,000 rare diseases, diagnosis usually takes about 5-7 years and treatments are uncommon or even nonexistent. These diseases are emotionally hard to cope with, so it is important for patients and families to find others who struggle with the same illnesses for support.                            



Thanks to the RareND student club, the State of Indiana now proclaims February 28th, 2015 as Rare Disease Day.


THANKS to everyone that participated!


Check out the article in THE OBSERVER about rare disease day.

"by Carolyn Hutyra '15"

Please visit our 2015 RDD Photo Gallery


A new publication from the Schafer lab on a rare breast cancer

Schafer Lab

Congratulations to the Schafer lab for a new publication in the journal “Cell Death and Differentiation”. The work, which is supported by the Boler-Parseghian Center for Rare and Neglected Diseases, focuses on inflammatory breast cancer (IBC), a rare malignancy with poor prognosis and a high mortality rate. Because it’s rare, IBC is not often recognized early enough. Adding to that, IBC does not present itself as a typical cancer, and is often mistaken for an infection, leading to incorrect treatment. Untreated IBC eventually “metastasizes” spreading to other organs. In this new publication, the lead author Cassie Buchheit, along with members of Dr. Zachary Shafer’s lab, demonstrates a new mechanism by which the cancer cells are able to detach and invade other parts of the body. It also paves the way to develop new drugs that target this mechanism. We look forward to more publications from the Schafer lab that will continue to shed light on rare cancers and push forward the development of therapies.


Thanks to generous donations from the Boler and Parseghian families we are now the Boler-Parseghian Center for Rare & Neglected Diseases

photo 89

Members of the Boler and Parseghian families with Center Director Dr. Kasturi Haldar and Dean Greg Crawford (College of Science) during the dedication ceremony, Saturday Oct. 11th. 

thank you letter




Clinical and Translational Seminar Series:

Dr. Meg Phillips

Professor - University of Texas Southwestern

pic of studentsFrom left to right:
Niraja Suresh, Francisco Fields, Stefan Freed, Katelyn Carothers, Micah Ferrel, Matthew Krusen, Dr. Meg Phillips, Lucy Smith, Trevor Kane and Nicholas Deason.

The Clinical and Translational Seminar Series organized by CRND hosted a presentation by Dr. Meg Phillips on October 3rd, 2014. Dr. Phillips is a leading researcher in the field of malaria drug development.  She shared the story of an emerging drug that targets a particular parasite enzyme with little toxicity to humans. During her seminar, Dr. Phillip described the unique journey of taking the process of drug discovery from a simple concept based in rational design in the test tube and following through all the way to studies in humans. This effort, which pulled in the expertise of a number of collaborators, has resulted in a promising new strategy for treating malaria, a disease that affects more than 300 million people globally and results in nearly a million deaths annually.
During her visit, Dr. Phillips met with students from the “Topics in Pathobiology” class, which is tied to the Seminar Series. Throughout the semester, the students read, present and discuss papers by the visiting speakers, and get a chance to meet with each visiting scholar over pizza.

Find out more about the Fall 2014 CRND seminar series


Thank you to all who participated in


The 2014 Rare Disease Research Symposium

Friday, October 10th 2:00pm – 5:00pm
DeBartolo Hall – Room 207

Click here for program


CRND Seminar Series

Fall - 2014





Please visit our 2014 MNID Photo Gallery


Click here for More Information (Registration is closed)



CRND Professor Receives American Cancer Society Grant

Schafer Lab From left to right:
Dr. Zach Schafer, Sydney Shuff, Josh Mason, Kelsey Weigel, Raju Rayavarapu and Cassie Buchheit

Dr. Zach Schafer, Biological Sciences, has recently received a grant from the American Cancer Society to continue ongoing work in his lab on breast cancer research. Dr. Schafer is particularly interested in metastasis, a process whereby cancer cells depart from the primary tumor and spread to other parts of the body. Typically, normal cells that depart from their organs die. However, cancer cells tend to survive and spread to other organs. By studying the molecules that prevent cancer cell death and enable its spread, Dr. Schafer and his group hope to bring about the knowledge to develop new therapies that prevent the spread of cancer, which is essential to the treatment of aggressive cancers. Dr. Schafer's lab also conducts similar studies in inflammatory breast cancer, a rare and highly deadly type of breast cancer with very few treatment options. 

Click here to see Dr. Schafer’s most recent interview with WNDU


CRND Professor

Fighting Ebola Virus

Dr. Robert Stahelin was recently interviewed by ABC57 News and WSBT News and Sports Radio regarding his research on the Ebola virus.  Dr. Stahelin provided various facts regarding the Ebola virus and reassured that the U.S. has no reason to be concerned at this time.  Currently his lab is identifying how the virus replicates in cells with the goal of using small molecule therapy to prevent its replication while better understanding the virus and to see what can be done to stop it.
Dr. Stahelin is a Professor of Biochemistry and Molecular Biology at the Indiana University School of Medicine-South Bend also an Adjunct Associate Professor of Chemistry and Biochemistry at Notre Dame. To watch the interview with Dr. Stahelin click ABC57 News or listen to the full interview at WSBT News and Sports Radio.


Dr. Robert Stahelin talks with the Notre Dame Alumni Association about his research on the treatment of the Ebola virus.



In Remembrance of: Dr. Guillermina Estiu

Dr. Guillermina

It is with a heart full of sadness that we let you know Dr. Guillermina Estiu, spouse of Guillermo Ferraudi of the Rad Lab, passed away on Friday, May 9th 2014 after several months of illness.

Dr. Estiu was a research assistant professor (Chemistry and Biochemistry).  CRND owes her a special debt because as founding member, she launched a highly successful computational modeling and chemistry core within the Center, which was then transitioned to a University Core on Computer Assisted Molecular Design, with Guille as Managing Director.   We are grateful for her dynamic and enthusiastic support to all members of the CRND and the University at large.   She had over 20 years of experience in computational chemistry, which she used to manage CRND and CAMD core operations.  She will be greatly missed for her vast knowledge base,  passion for chemistry and selfless personality.



See our Video on Malaria Research


Local Middle School Students Visit Notre Dame to Learn about Rare Diseases


On Thursday March 6th, a group of students from Lake Shore Middle School student council visited Notre Dame to learn about rare diseases. The students had lunch with Dean Greg Crawford (College of Science) and toured the Notre Dame campus. During their visit at CRND, Notre Dame students from the RareND club demonstrated how difficult it can be for rare disease patients to find diagnosis and expert care through an interactive game.



Dr. Md. Suhail Alam (Haldar lab) introduced the students to his research in Niemann-Pick Type C (NPC) disease, which is a neurodegenerative rare disease that affects children and teens. A discussion between the visiting students and Notre Dame researchers demonstrated how interested and enthusiastic they are about learning and raising awareness for rare diseases. They also shared their plans for a 5K fundraising marathon to benefit rare disease awareness.




CRND Welcomes New Outreach Coordinator

The Center for Rare and Neglected Diseases welcomes Barb Calhoun as the new outreach coordinator. Barb’s main role will be to assist patient families with resources and information regarding rare\Barb is a pediatric nurse practitioner with previous experience in school health, hospital nursing and research. She really enjoys meeting/working with families and her goal is to become a valuable resource for the rare disease patient community. In addition, Barb will be working closely with Notre Dame Students involved in the Rare ND club and Dr. Kasturi Haldar’s class, “Clinical Research in Developing Health Networks for Rare and Neglected Diseases.”  If you or a family member is interested in learning more about a rare disease, finding specialists, support groups or other resources, please contact Barb Calhoun.



World Rare Disease Day Celebration 2014

group photo


Notre Dame celebrates World Rare Disease Day


Published: February 24, 2014          

Author: Stephanie Healey


The Center for Rare and Neglected Diseases (CRND) and the Rare Health Exchange (RHE) celebrated World Rare Disease Day on Saturday, Feb. 15 at the Notre Dame Conference Center.  World Rare Disease Day is a global event that was first launched in 2008 to raise awareness among the general public and decision-makers about rare diseases and their impact on patients’ lives.

“We began celebrating rare disease day in 2009,” said Shahir Rizk, director of external programs for the CRND and research assistant professor of biological sciences. “Last year, we tried out the public forum format and found it to be well received. It gives Notre Dame a chance to be engaged with the local community and to provide a forum for rare disease patients and families to interact with researchers, physicians and students.” The daylong symposium was dedicated in memory of Tylor White-Richardson and Riley Smith, two patients who recently passed away from Niemann-Pick Type C (NPC) disease, a rare cholesterol storage disorder that affects approximately one in 100,000 people.

Elizabeth Berry-Kravis ’79, M.D., Ph.D., professor of pediatrics, neurology, and biochemistry at Rush University Medical Center in Chicago, participated in a panel about experimental drug treatments.  She works with families whose children have NPC. Berry-Kravis explained that for many years, the only option for NPC treatment was to provide supportive care to help alleviate the symptoms, but “thanks to the Parseghian Foundation, there has been a significant increase in NPC research in the last 20 years.”

Berry-Kravis was able to get approval from the FDA through the Investigative New Drug (IND) Program to provide an experimental treatment for her patients using cyclodextrin, a small molecule therapy, which is also being tested at other clinical sites.  “These diseases have ups and downs so you need to look at trends over time, but we are seeing early subtle, but promising results,” said Berry-Kravis.

Several attendees shared their experiences in open forum focused on living with rare diseases.  Coley Mrozcek shared his experience with X-Linked Hypophosphatemia (XLH), a disease that disrupts the assimilation of vitamin D and phosphorus in his body and causes bone malformation. His mother, three siblings, and daughter all have XLH.  “It is different being a patient of XLH, and having a child with it,” Mrozcek explained. “My daughter is 12 years old. She has difficulty running because of the way her legs have formed and other children are starting to notice. A better form of treatment is a priority for me and the way the research is going is encouraging for me as a parent.”

Cindy Riemersma came with her 21 year old daughter, Jyl, who was diagnosed with Glucose Transporter Deficiency Syndrome at the age of four. Jyl was only the 15th person in the world diagnosed with the syndrome. There are now more than 250 people diagnosed worldwide, indicating the importance of diagnosis.  


A major theme that emerged from the discussion was that all of the patients and families present had taken ownership of their situations and worked tirelessly to get the answers and treatments they needed because information and resources are much more limited with rare diseases. Muriel Finkel of the Amylodosis Support Groups Inc., a member of the National Organization of Rare Diseases, stressed the importance of service organizations that cater to specific rare diseases. These organizations can help connect patients to resources, such as treatment options, counseling and other patient families.

The second half of the day included a poster session and research presentations from Notre Dame students and faculty.  ESTEEM students Bianca Fox and Yuan Gao described the RHE program, a collaboration of students and patient families working together to develop a database to help rare disease patients and their caregivers.  Over the last five years, many families including the White-Richardson and Smith families have visited with Notre Dame students and faculty to help develop the RHE.   


Four Notre Dame researchers discussed their work on various lysosomal storage diseases. Shaun Lee, assistant professor of biological sciences, and Tony Serianni, professor of chemistry and biochemistry, described their research collaboration on Sanfilippo syndrome, a disease which prohibits an enzyme from properly breaking down complex sugars. In addition to developing new therapies, their work also helps predict whether a patient will respond to two major types of treatments that are currently being developed for this disease.  Md Suhail Alam, a postdoctoral associate in biological sciences who works with Kasturi Haldar, the Rev. Julius Nieuwland, C.S.C. Professor of Biological Sciences and James C. Parsons and Carrie Ann Quinn Director of the Center for Rare and Neglected Diseases, reported on the first plasma biomarker for neurodegeneration that can be used to monitor whether NPC patients on a therapy are improving in brain disease. Olaf Wiest, professor of chemistry and biochemistry, discussed how he uses powerful computers to find FDA-approved drugs that can be repurposed to treat rare diseases like NPC.

The second research session focused on rare cancers, which are often difficult to diagnose and have a poor prognosis. Başar Bilgiçer, assistant professor of chemical & biomolecular engineering and concurrent assistant professor of chemistry and biochemistry, described his work on developing nanoparticles to target multiple myeloma and Laurie Littlepage, Campbell Family Assistant Professor of Cancer Research, explained how her work is trying to compare the biology of a rare breast cancer that affects Kenyan women with cancers found in North America. In addition, Cassandra Buchheit, a graduate student in biological sciences who works with Zachary Schafer, Coleman Assistant Professor of Cancer Biology, spoke about her work with a rare inflammatory breast cancer that is often misdiagnosed as an infection.


Mike Hamerlik, CEO of WPS Health Insurance joined one of the patient family representatives to explain how new health insurance laws will impact rare disease patients. This panel was particularly informative to the families who have traditionally had few options when it comes to health insurance.


To conclude the seminar, the group completed a rare disease quiz prepared by the newly minted RareND club, which reminded the audience how much still needs to be done to raise awareness for rare diseases.  They also sang a new version of the Notre Dame fight song to rally the fight against rare diseases.

Please visit our 2014 RDD Photo Gallery



open CRND

2014 Agenda.... CLICK HERE



Riley Smith

Riley pix


It is with a heavy heart that we let you know that Riley Smith, daughter of Trent and Julie Smith, passed away, January 19th after a brave battle with Niemann-Pick Disease, Type C.  Riley and her family represented many individuals with the disease and helped raise awareness and funds.  They also helped Notre Dame start developing undergraduate studies on rare diseases and collaborative programs like Rare Health Exchange.   Riley loved sports and her strength and perseverance were always inspirational to us at ND.

You can also view here a short version of the video CRND made with the Smith family in 2011. Filmed at the University of Notre Dame by Liz Hodge (Foundation for Biomedical Research), SurvivorTales: Niemann-Pick Type C tells the story of Riley Smith and her brother Keaton Smith suffering from a rare and fatal genetic disease and research that could save their lives. It stars the Smith Family, Dr. Kasturi Haldar and Cindy Parseghian. The show won a Telly Award in 2011

If you wish to see the full version please email





Tylor White-Richardson

(9/11/1996 – 12/12/2013)


Tylor Pics

On December 12th, 2013, Tylor White-Richardson passed away after a brave battle with Niemann-Pick Type C (NP-C) disease. Tylor was a budding ball player till he was struck by symptoms that took six years to diagnose as NP-C  He and his family represented many individuals with the disease and helped raise awareness and funds. Tylor and his family helped Notre Dame undergraduates better understand NP-C from a patient perspective and learning the challenges of having a rare disease. His outgoing personality and sense of humor helped all of us at CRND to see the importance of seeking treatments no matter the challenge. Our thoughts and prayers go out to Tylor’s family in this difficult time.


In remembrance of Ty’s life please feel free to post caring memories. Please click here




CRND Scientist’s Publication Featured in News Story

Dr. Basar Bilgicer was recently featured in a news article describing his lab’s latest publication. The work highlights efforts to engineer a new type of inhibitor that can prevent type-I hypersensitive reactions, which can be life-threatening, to common food and drug allergens, such as peanuts & shellfish.

Dr. Bilgicer , who serves on the CRND steering committee, is an assistant professor at the Notre Dame department of chemical and biomolecular engineering and holds an appointment in the department of chemistry and biochemistry.

Basar Bilgicer

Dr. Basar Bilgicer


Thank You 1

Thank You 2


Thank You 3


Click here for More Information (Registration is closed)


CRND Seminar Series

Fall - 2013




CRND Faculty Named IUSM Showalter Scholar


Congratulations to Dr. Robert Stahelin for being selected as an Inaugural Showalter Scholar by the Indiana University School of Medicine. Dr. Stahelin is an assistant professor of Biochemistry and Molecular Biology and an adjunct professor of Chemistry and Biochemistry at Notre Dame. He is an active member of CRND with his research focused on understanding of lipid processing in a number of deadly pathogens including the Ebola virus and the parasite that causes malaria. Dr. Stahelin will hold the title of “Inaugural Showalter Scholar” for three consecutive years along with funds for his laboratory research.

Please join us in congratulating Dr. Stahelin on this outstanding achievement!


CRND Releases new video on "Malaria Research"


Malaria from CRND on Vimeo.

CRND Launches a New Computational Core









The Center for Rare and Neglected Diseases announced the launching of the computer aided molecular design (CAMD) core facility. The CAMD core will be a state-of-the-art facility for computational chemistry.  The core is based on a pilot project that was initiated to assist drug discovery and development in CRND. However, many groups in a variety of research areas ranging from chemistry, biochemistry, molecular, cell and environmental biology and computer sciences, both at Notre Dame and other universities also have needs for computer assisted molecular design, often in critical, and early stages of a project.  Hence, the CAMD core will be a valuable resource for all to use computational approaches to study the complex interactions of small molecules in medicinal, industrial or environmental applications.

In spring 2011, the CRND launched two pilot projects to assist drug and insecticide discovery and development. The first arose as a need for computational analysis of the results from a screen of chemical libraries from Eli Lilly & Co to discover and develop new drugs against the malaria parasite. This project is in partnership with the Medicines for Malaria Venture (MMV), a virtual pharma agency based in Switzerland, supported by the Bill and Melinda Gates Foundation and multiple governments.   The second project was the study of receptors known as G-protein coupled receptors (GPCRs) as insecticide targets. This work is supported by the Army to develop a new family of insecticides.  It has fostered collaborations with the University of Michigan and Stanford University including the Nobel Laureate Dr. Brian Kobilka. GPCRs are crucial proteins in human health, targeted by approximately 40% of all drugs currently on the market. GPCRs have the potential to provide the same promise as targets for insecticides. 











Dr. Guillermina Estiu, a research assistant professor (Chem & Biochem) will be the managing director of the CAMD core. Dr. Estiu has already been an active member of the CRND pilot projects, and she will utilize her experience of over 20 years in computational chemistry to manage the CAMD core operations. 

Dr. Olaf Wiest (Chemistry and Biochemistry) and Dr. Jesus Izaguirre (Computer Science) will oversee the operations of the CAMD core facility. Both Dr. Wiest and Dr. Izaguirre were key to nucleating the pilot project within CRND.  The success of the pilots as well as requests for assistance for other projects laid the groundwork for developing the core.  Its launch was made possible by the support of the CRND Steering Committee and the Office of the Vice President of Research, Dr. Bob Bernhard.

Pilot funds are available for investigators who have not used computer assisted molecular design, but feel it will assist with their research. Professors Wiest, Izaguirre and Estiu will review and prioritize project requests. They can also assist with proposal writing/project development and will be available for consultation on a range of CAMD methodology.


World Rare Disease Day 2013

On Saturday February 23rd, CRND organized a daylong event to commemorate World Rare Disease Day. The event brought together Notre Dame researchers and students with physicians, patients and their families to discuss the everyday challenges and the most recent breakthroughs in managing rare diseases. The event, which is open to the public, was designed to give a voice to all the different groups involved with panels that interact with the audience. We heard from researchers and students about the new developments in drug design. We heard from patient families about the challenges of having a member with a rare disease and possible ways to address these challenges. Additionally, Dr. Carrie Quinn, MD, along with ND students, touched on some ethical questions that face physicians and patients in managing rare diseases. The event was successful in bringing together diverse groups who share the common goals of raising awareness and finding cures for rare diseases.



The New SPRING 2013 Issue of Signal - CRND 's Newsletter

The Clinical-Translational Seminar Series -Dr. Padmini Salgame

(Above, from the left) November 30, 2012. Drs. Padmini Salgame. Patricia Champion, and Shahir Rizk enjoy a moment on the quad following Dr. Salgame's seminar at Geddes Hall.

On her recent visit to the University of Notre Dame's Center for Rare and Neglected Diseases, Professor Padmini Salgame addressed students and faculty on the topic of "Intrinsic and Extrinsic Factors Regulating Host Anti-tuberculosis Defense." Dr. Salgame's seminar focused on two central stories. The first part of her lecture disclosed her lab's examination of both innate and acquired immune responses to Mycobacterium tuberculosis (MTB) and the role of T-regulatory cells. Salgame highlighted some of what is and is not known about the functioning of the tuberculosis granuloma, memory T-cells, and biosignatures associated with individual adaptive immune responses and the susceptibility to infection.

The second part of Salgame's talk looked at research on co-infections of MTB and helminthic parasites. Salgame described her investigation into the pathogenesis of both diseases in co-infection, particularly how the effects of the immune responses related to one infection effects the progression of infection in the other disease. For example, helminthic infection raises Th2 cell responses. and those in turn, have the effect of down regulating the Th1 responses that are so critical in resisting MTB infections. The timing of infections is crucial to determining the interplay between the body's immune responses to the two diseases. TB has a high prevalence in many regions where helminthic diseases are endemic, and it is critical to discover how these co-infections modulate the course and outcome of MTB infections. Salgame's current examinations of helminth infections and the actions of immune responses in impeding MTB progression, together with her work in innate and acquired immunity, are providing significant insights that will aid in the the development of vaccines and treatments for TB.

Following her seminar, the gracious Director of Graduate Medical Research for the University of Medicine and Dentistry of New Jersey warmly welcomed graduate students in Drs. Champion and Lee's class for lunch and a relaxed discussion on a variety of topics (see photo below of the students with Dr. Salgame).

(Below, from the left) Graduate students from Drs. Champion and Lee's Topics in Pathobiology class - from the left, Rachel Schluttenhofer, Emily Williams, George Kennedy, Jennifer Zupkosky, Victoria Smith, Dr. Salgame, Jerome Fru Cho. (Photos: C Stackowicz, 2012)


The Clinical-Translational Seminar Series -Dr. Vernon Carruthers

(Above) Dr. Carruthers addressing the CRND CTSS audience. (Photo: C Stackowicz, 2012)

November 16, 2012. CRND's Director, Kasturi Haldar introduced Dr. Vernon Carruthers as "someone who knows more about the biology of cells and parasitic invasion than anyone I can think of." High praise considering that Drs. Carruthers and Haldar both share decades long careers investigating the mechanisms of parasitical infections. Carruthers and Haldar also enjoy alumnus status from The Rockefellar University, where they completed their postdoctoral work in Dr. George A.M. Cross's Laboratory of Molecular Parasitology. Carruthers was there in the early 1990's and Haldar completed in the late 1980s. Since then, each has pursued the study of the pathogenesis of a disease caused by a parasite. Carruther's identifies his protozoan parasite Toxoplasma gondii as "a cousin of the malaria parasite", which has been the focus of Haldar's investigations for many years. Both parasites are responsible for billions of infections annually, although Toxoplasma gondii creates a serious disease condition in only tiny percent of the 2 billion people who contract the infection. Generally, adults with healthy immune status manage to keep the parasite in an encysted state in the body and most of the people who become seriously ill from Toxoplasma gondii are infants or people who are immunocompromised due to another condition (e.g., HIV, organ transplant recipients, or chemotherapy patients).

Dr. Carruthers is currently a Professor in the Department of Microbiology and Immunology at the University of Michigan Medical School where his lab is focused on the study of Toxoplasma gondii as a "model" pathogen. A model pathogen is an organism that is extensively researched with the hope that discoveries about its biological functioning may also be extrapolated to understand the workings of similar organisms. According to Carruthers, the Toxoplasma gondii model works as a model for intracellular paracitism "because of its genetic and biochemical tractability, well defined cellular structure, and the availability of excellent rodent models of disease" (Carruthers Lab page).

Carruther's seminar was entitled, "Infection strategies of the highly successful neurotrophic parasite Toxoplasma gondii."


The Clinical-Translational Seminar Series -Dr. Timothy Grese

(Above, ND graduate student Stefan Freed and Dr. Timothy Grese)

November 2, 2012. Dr. Timothy Grese, Chief Scientific Officer for Lead Generation and External Innovation Discovery in Chemistry Research and Technology at Eli Lilly and Company, was welcomed to the CRND's Clinical Translational Seminar Series where he presented, "Open Innovation Drug Discovery (OIDD): A New Platform for Academic-Industrial Collaboration." The platform for collaboration discussed by Dr. Grese addressed a problem that is all too familiar to investigators in rare and neglected diseases research; the lack of financial incentives for the drug industry to invest in finding therapeutics for small or poor populations and the lack of resources available to non-profit universities to advance major projects in drug development. The new model for collaboration described by Grese can allow universities to use Lilly resources for their academic research into areas such as drug design, data analysis, and assay development.

The Clinical-Translational Seminar Series -Dr. George Dimopoulos

"Basically, no one had published on the circadian biology of the mosquito for a very long time. Finally, Dr. Dimopolous published his paper on photic inhibition of blood-feeding in Anapheles gambiae. This paper was crucial to my own research. Dr. Dimopoulos' work and generous advice to me over the years was really valuable to my project and eventual publication with Dr. Duffield."

-- Sam Rund, Ph.D. Cand. in Biology at Notre Dame


(Above: George Dimopoulos and Samuel Rund . Photo: C. Stackowicz, 2012)

October 26, 2012. Dr. George Dimopoulos presented his cutting-edge seminar for CRND to a delighted gathering of faculty and students whose research is focused in infectious diseases and global health. Dr. Dimopoulos's discoveries in vector control at Johns Hopkins Malaria Research Institute are very exciting because of their potential to use the mosquito's own immune system and gut microflora as means of attenuating its transmission of deadly diseases, namely malaria and dengue fever.

Dr. Dimopoulos began with maps. The first illustrated the gradual contraction of malaria endemic areas around the world. Dimopoulos pointed out the key role targeting the vector had played in elimination over 100 years. In the second illustration, Dimopoulos described the emerging growth pattern of dengue fever. According to Dimopoulos, his group works on understanding the processes of infection and immune response to both diseases, in projects that are distinct, but synergistically related. The synergy arises in the broadening of the overall knowledge about the biological processes comprising the mosquito's defense against pathogens, the understanding its genetic structures, and the development of specialized tools that serve a variety of purposes.

Dimopoulos' lab has made significant progress utilizing advanced gene expression analysis methods and technology to analyze the mosquito's functional genomics and characterize pathways, which regulate immune response and resistance to infection. In fact, the Dimopoulos group's project page reports "the first full genome microarrays for Anopheles gambiae, Aedes aegypti, Culex pipiens and Plasmodium berghei" were developed by his lab.

Dimopoulos' discussion of the role of mosquito's own innate immune system, which has evolved to protect it from the malaria parasites it ingests while feeding, summarized a number of experiments leading to the characterization of the "Imd pathway." This pathway plays a crucial role in mediating the mosquito's biological ability to fight off infection. The Dimopoulos Lab's success in describing the progressive immunological responses of the mosquito at the level specific genetic transcriptions is a powerful advance towards gene-based interventions. These interventions will eventually assist the mosquito in resisting infection and consequently reduce it's transmission of the disease to humans. Dimopoulos is careful to underline that the current approach his research aims at is a kind of genetic jumpstart of an existing immune response against the infection based on the mosquito's innate characteristics. The idea, according to Dimopoulos, is to "make the gene turn on earlier" in the infection response and to "not introduce something new."

A key finding of the Dimopoulos group is that specific microflora in the mosquito's gut are critical to its defense against parasitic invasion and the production of sporozoites. It is these sporozoites that infect the salivary glands of the insect and eventually find their way into new hosts when the mosquito feeds.

Visit the Dimopoulos groups project page to read about their advances in vector control research, many of which were described by Dr. Dimopoulos in his brilliantly accessible presentation. Indeed, a number of international students and researchers commented with pleasure on how easy it was to follow Dimopoulos's comprehensive and detailed exposition. In the words of Leonardo DaVinci: “Simplicity is the ultimate sophistication.”

George Dimopoulos, Ph.D., M.B.A. is a Professor in the Department of Molecular Microbiology and Immunology at Johns Hopkins University. He is also the Director of the Parasitology Core Facility and Deputy Director of the Malaria Research Institute, which are part of Hopkins' Bloomberg School of Public Health.

- Building Discovery In Vector Control -

Rund SS, Hou TY, Ward SM, Collins FH, and Duffield GE. (2011). Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae. Proc Natl Acad Sci USA. 2011 Aug9; 108(32):E421-30.

Das, S., and Dimopolous G. (2008). Molecular analysis of photic inhibition of blood-feeding in Anopheles gambiae. BMC Physiology 16; 8(1):23.

The Clinical-Translational Seminar Series -Dr. Dara Frank

(Above) Dr. Dara Frank met with graduate students in the Clinical Translational Seminar and Readings in Pathology Course. From the left, Jeannie Hoang, George Kennedy, Victoria Smith, Professor Frannk, Rachel Schluttenhofer, Emily Williams. (Photo: C Stackowicz, 2012)

On October 12, 2012, Dr. Dara Frank visited the CRND and delivered a fascinating lecture on her lab's penetration of the opportunistic strategies of a pathogen, which is responsible for significant morbidity and mortality in humans and animals. Dr. Frank's seminar, "Molecular and Cellular Analyses of the Pseudomonas aeruginosa Cytotoxin, ExoU" further illuminated the work she described a 2011 paper outlining her team's discovery of the role of Ubiquitin in the toxic effects of P. aeruginosa (Anderson et al., Molecular Microbiology 82(6) 1454-1467). Graduate students of Drs. Patricia Champion and Shaun Lee had read Frank's paper in preparation for the study's principal investigator's visit. Dr. Frank is a Professor of Microbiology and Molecular Genetics at the Medical College of Wisconsin and the Director, Center for Infectious Disease Research.

Dr. Frank's research is focused on the interaction between hosts and bacterial factors involved in infections with Pseudomonas aeruginosa and Francisella tularensis. She explores the genetic regulation of exotoxin synthesis, examining the relationship between the expression of toxins (e.g., toxins injected into eukaryotic cells that compromise the innate immunity in hosts), the pathogenesis of the bacterium, and host responses.

In her seminar, Dr. Frank described the process by which the common bacterium, P. aeruginosa, carries the effector protein, ExoU, in an inactivated state where it cannot harm the bacterium. Once the bacterium infects a host cell, however, a protein in the host, Ubiquitin, activates ExoU and allows it to degrade the membrane of the host's eukaryotic cells. Commenting on Dr. Frank's seminar, Dr. Shahir Rizk praised her "very elegant experiment" for demonstrating that the host protein is indeed required for the toxic effect of this dangerous bacterial protein to take effect.

Pseudomonas aeruginosa is an opportunistic pathogen found in skin flora, as well as soil, water, and a variety of human environments. In humans and animals with compromised immunity, the bacterium may gain entry and colonize body organs with potentially fatal consequences. In medical facilities, the bacterium may be found in medical equipment or implements and have disastrous results, particularly in the case of biofilms of P. aeruginosa, which are particularly resistant to treatment with antibiotics.

Dr. Frank's lab played a leading role in the discovery and characterization of the "P. aeruginosa type III system," which mediates the delivery of toxins. Her lab continues to explore enzyme inhibitors, antibody reagents, and vaccines, which may potentially neutralize these damaging toxins.


The New Fall 2012 Issue of the Signal - CRND 's Newsletter

The new issue of CRND's Signal (vol 2, is 1) for the Fall of 2012 covers the 2nd Annual Midwest Neglected Infectious Disease Meeting, Dr. Patrick Duffy's Clinical-Translational Seminar, the CRND Data Club meeting with Dr. Zach Schafer and Cassie Buchheit's presentation on inflammatory breast cancer research, ND undergraduate and Rare Health Exchange projects with the National Organization of Rare Diseases, ND malaria, rare cancer and tuberculosis research updates, publication news for Dr. Innocent Safeukui and Dr. Patricia Champion's group, and a faculty spotlight on Dr. Shahir Rizk of the CRND.

The Clinical-Translational Seminar Series - Dr. Carole Long -

(Above) Dr. Carole Long, Chief of the NiAID/NIH Laboratory of Malaria and Vector Research's Malaria Immunology Section and Director of the PATH Malaria Vaccine Initiative Growth Inhibition Assay-Reference Center. (Photo: C Stackowicz, 2012)

October 5, 2012. Dr. Long's seminar to CRND faculty and students entitled, "Progress toward development of a malaria vaccine" provided a comprehensive overview of the current status of vaccine development for various stages of malaria infection. Her presentation reviewed considerations for evaluating new vaccine targets and engaged the audience in an intriguing reflection on what is already known about the acquisition of immunity in endemic areas.

Dr. Long applauded the recent progress in vaccine development due to an expansion of funding and new technologies that have accelerated research. Dr. Long cited the significant advance represented in 2011 with the publication of "First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children" by Agnandji et al. (NEJM 365(20); 1863). This publication by a group from the Albert Schweitzer Hospital in Lambarene, Gabon, reports on an ongoing phase 3 study of over 15,000 children in seven African countries with respect to the malaria vaccine RTS,S/AS01. Dr. Long is the director of the PATH Malaria Vaccine Initiative, which together with GlaxoSmithKline Biologicals, is funding this research. Agnandji et al. conclude in their NEJM article: "The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children."

Following her presentation, Dr. Long joined ND graduate students for lunch and a lively informal discussion of her research and the extraordinary scope and achievement of the PATH Malaria Vaccine initiative.


The Clinical-Translational Seminar Series - Dr. Jose Bufill-

(Left) Jose A. Bufill, M.D., F.A.C.P. Director, Cancer Genetics Program, St. Joseph Regional Medical Center, South Bend. Clinical Investigator, Northern Indiana Cancer Research Consortium. Private practice in Hematology-Oncology, Elkhart & South Bend, In.

September 21, 2012 - Dr. Jose Bufill's contribution to the CRND Clinical-Translational Semininar Series, "Preliminary observations using N-acetylcysteine for refractory TTP: An opportunity for new management strategies?" engaged both students and faculty in an exciting translational discovery underway in their own community. Dr. Bufill has been treating a patient in South Bend with refractory, relapsing thrombotic thrombocytopenic purpura (TTP), a rare disorder of the blood-coagulation system. Using N-acetylcysteine (NAC), Dr. Bufill has observed noteworthy temporary therapeutic benefits without significant side effects.

Dr. Bufill's presentation described the pathophysiology of TTP, a serious and life-threatening disorder caused by dysfunction of the normal metabolism of the Von Willibrand factor (VWF). According to the National Heart, Lung, and Blood Institute: "In TTP, blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop." (To read more from the NHLBI website).

TTP may be either a congenital or inherited condition and is prone to relapse since the standard therapy of plasma exchange does not remedy the underlying cause. Recently, N-acetylcysteine (NAC) has shown promise in animal models. Dr. Bufill discussed further laboratory and clinical studies projected for NAC related compounds and their potential benefits for patients with this rare disorder.


Dr. Patricia Champion Publishes in Molecular and Cellular Proteomics

September 2012 - Dr. Shahir Rizk, CRND's Director of External Programs, recently spoke to UND's Dr. Patricia Champion about her new publication in Molecular & Cellular Proteomics. Dr. Rizk describes the core finding, "identifying key features of tuberculosis infection and the development of a new method for identifying important factors that tuberculosis bacteria use to infect human cells" in the upcoming CRND newsletter, The Signal. Seed funding was provided by a CRND proteomics grant. See the abstract for Champion's innovative study below. (Left, Dr. Patricia Champion)

"Direct Detection of Bacterial Protein Secretion Using Whole Colony Proteomics." Matthew M. Champion, Emily A. Williams, George M. Kennedy, and Patricia A. DiGiuseppe Champion. Molecular & Cellular Proteomics. First Published on May 10, 2012. OA publication: September 1, 2012 Molecular & Cellular Proteomics, 11, 596-604.

Bacteria use a variety of secretion systems to transport proteins beyond their cell membrane to interact with their environment. For bacterial pathogens, these systems are key virulence determinants that transport bacterial proteins into host cells. Genetic screens to identify bacterial genes required for export have relied on enzymatic or fluorescent reporters fused to known substrates to monitor secretion. However, they cannot be used in analysis of all secretion systems, limiting the implementation across bacteria. Here, we introduce the first application of a modified form of whole colony MALDI-TOF MS to directly detect protein secretion from intact bacterial colonies. We show that this method is able to specifically monitor the ESX-1 system protein secretion system, a major virulence determinant in both mycobacterial and Gram-positive pathogens that is refractory to reporter analysis. We validate the use of this technology as a high throughput screening tool by identifying an ESAT-6 system 1-deficient mutant from a Mycobacterium marinum transposon insertion library. Furthermore, we also demonstrate detection of secreted proteins of the prevalent type III secretion system from the Gram-negative pathogen, Pseudomonas aeruginosa. This method will be broadly applicable to study other bacterial protein export systems and for the identification of compounds that inhibit bacterial protein secretion.


The Clinical-Translational Seminar Series- Dr. Patrick Duffy -

September 7, 2012 -(Above) Patrick E. Duffy, M.D., Chief of the Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH presented "Translating Malaria Immunity into Malaria Vaccines." (Photo, K. DeCloedt, 2012)

About The Inaugural CTSS Seminar

This fall, the CTSS seminar series was kicked off with an exciting presentation by Dr. Partick Duffy, discussing the recent progress in the fight against malaria. Dr. Duffy is a clinical researcher, whose work at the National Institutes of Health has taken him all around the world to malaria endemic areas where help is most needed. Often, such areas experience high levels of poverty and political turmoil. Most recently, Dr. Duffy found himself in the midst of a coup d’etat in Mali while training a group of students.

Dr. Duffy’s talk gave a taste of what’s to come. Several speakers are lined up throughout the semester with topics ranging from the study of infections by parasites, bacteria and viruses, to the characterization of the immune response to those infections, as well as the work carried out in developing novel therapeutic agents.

~ Dr. Shahir Rizk, Director of External Programs for the CRND


The Rare Health Exchange - RHE

The Rare Health Exchange (RHE) website is a web-based student collaboration to advance research, education, advocacy and patient support for the rare disease community. The RHE initiative has been supported from incubation to launch by a diverse group of sponsors including the Deans of the Colleges of Science and Engineering, the Office of the Vice-President of Research, the FISH non-profit organization, the Center for Social Concerns and the leadership of the CRND. Visit the Rare Health Exchange website.



About The Center for Rare and Neglected Diseases

Science for Society

Around the globe, people are suffering and dying from diseases that have generally been ignored by major pharmaceutical companies because the potential financial rewards for developing new drugs and vaccines to treat them are insignificant. These are the rare and neglected diseases of the world. There are thousands of rare diseases, typically defined as those, which afflict less than 200,000. Among them are cystic fibrosis, thalassemia, Niemann-Pick C disease, and several of the rare forms of cancer. Neglected diseases, by contrast, can affect billions, but like their rare counterparts, have been ignored by researchers. This is especially prevalent in the developing world and in pockets of grinding poverty in developed nations, where the populations suffering from illnesses such as tuberculosis, malaria, and lymphatic filariasis do not have the money to buy drugs and vaccines, giving pharmaceutical companies little incentive to develop treatments that cost far more than could ever be recouped through reasonable prescription prices. The result is a gaping hole in healthcare—one which Notre Dame is uniquely positioned to fill.


Rare Diseases: those which afflict less than 200,000. Examples are cystic fibrosis, thalassemia, Niemann-Pick Type C Disease, adrenolekodistrophy and several forms of cancer.

Neglected Diseases: diseases of poverty, lymphatic filariasis disease pathologies of TB and Malaria.


Where We Are:

University of Notre Dame
Center for Rare and Neglected Diseases
Galvin Life Science Building
Notre Dame, IN 46556
Email at:
Phone (574) 631-3372
Fax (574) 631-9788





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