RYR-1 Foundation Research Grants

The RYR-1 Foundation's primary mission is to find an effective treatment or cure for RYR-1-related diseases. In service of that mission, the RYR-1 Foundation has distributed approximately $1 million since 2014 in research funding. We look forward to building on the results of our current and prior research, with a focus on exploiting the recently developed mice that have RYR-1 mutations and muscle weakness. Please click HERE for the 2019 Grant Application.


The RYR-1 Foundation has a rigorous grant-review process, and we are proud of the principal investigators that have received prior funding from our organization. Please see details below. 

Alan Beggs, PhD "Drug Discovery for RYR-1 Myopathies Using Zebrafish Models"

Dr. Alan Beggs is Sir Edwin & Lady Manton Professor of Pediatrics at Harvard Medical School and Director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, where he also directs a research group in the Division of Genetics and Genomics. Dr. Beggs’ research has focused on genetic approaches to understanding a variety of rare diseases, particularly focusing on RYR-1 and related congenital myopathies, and using that information to understand the pathophysiology and develop therapies for these conditions. His group has been active in analyzing genetic changes in individuals with RYR-1 myopathies and in using zebrafish with RYR-1 mutations as a model system to screen for drugs to treat this condition.  

Robert T. Dirksen, PhD - “Drug Discovery and Validation for RYR-1-Related Myopathies” and “HITI-Mediated Gene Editing for RYR-1 Myopathy”

Dr. Robert Dirksen is the Lewis Pratt Ross Professor and Chair of Pharmacology and Physiology at the University of Rochester Medical Center. Dr. Dirksen obtained his BS in Biology and Chemistry from the University of Notre Dame, and MS and PhD in Pharmacology from the University of Rochester. Dr. Dirksen is an outstanding scientist who has focused much of his scientific efforts on understanding the underlying defects of skeletal muscle in patients with Myotonic Dystrophy, Malignant Hyperthermia, Central Core Disease, and other RYR-1-related diseases. His particular focus has been on understanding the control of calcium movements in muscle and the complex relationship between altered calcium movements and abnormal muscle function. His work has shown that dysfunction in calcium flow through RYR-1 calcium channels is the underlying cause of muscle weakness in patients with RYR-1 muscle disease. 

 

His work has been funded by the National Institutes of Health, the Muscular Dystrophy Association, and the RYR-1 Foundation among others. He has published over 130 original research articles and reviews in leading scientific journals and has given 

numerous invited lectures. Dr. Dirksen is the Past-President of the Society of General Physiologists, Chair of the MHAUS Professional Advisory Committee, and serves on the editorial boards of several journals, including the Journal of General Physiology, Skeletal Muscle and Frontiers in Skeletal Muscle Physiology. He was Chair of the 2015 Gordon Research Conference on Muscle: Excitation-Contraction Coupling and has served on several NIH Study Sections related to muscle biology and disease.

 

Dr. Dirksen is a member of the Scientific Advisory Board (SAB) of the RYR-1 Foundation.

James Dowling, MD, PhD - Drug Discovery and Validation for RYR-1-Related Myopathies” and "Cas9-Mediated Point Mutagenesis of RYR-1"

Dr. Dowling is a clinician-scientist who is focused on gene discovery and therapy for childhood muscle diseases. He is an Assistant Professor of Neurology at the University of Toronto and a neurologist at the Hospital for Sick Children in Toronto.

 

Dr. Dowling is considered one of the world’s leading experts in RYR-1 muscle disease. His research spans the continuum from new gene discovery to disease pathogenesis in genetically modified organisms. He is also engaged in both targeted and non-biased drug discovery for RYR-1-related myopathies. His laboratory employs both the zebrafish and mouse model systems, along with complementary in vitro analyses. Dr. Dowling is the recipient of numerous NIH and private foundation research grants, and has recently published detailed results of his RYR-1-related research.

Dr. Dowling is a member of the Scientific Advisory Board (SAB) of the RYR-1 Foundation.

Angela Dulhunty, MD, PhD - “Developing Animal Models with an RYR-1 Mutation and Clinical Phenotype for the Purpose of Evaluating Cell and Molecular Mechanisms of RYR-1 Disease”

Dr. Angela Dulhunty graduated from The University of Sydney, Australia, in 1969 with a Bachelor of Science degree and Honours in Physiology. She obtained a PhD from the University of NSW in 1973 presenting a thesis describing muscle electrophysiology studies carried out with Professor Peter Gage. She was then awarded a Muscular Dystrophy Postdoctoral Fellowship to work at the University of Rochester (NY) with Professors Paul Horowicz, Clara Franzini-Armstrong and Camillo Peracchia. She returned to Australia in 1975 and established a Muscle Research Laboratory in the Department of Anatomy at The University of Sydney. In 1982 Dulhunty, with Professors Peter Gage and Peter Parry, was awarded and a Centre of Excellence for Nerve Muscle Research at the University of NSW.  The Centre moved to the Australian National University in Canberra in 1984, where Dulhunty re-established the Muscle Research Laboratory. She was awarded a DSc degree by the University of NSW in 1988 for her extensive research into muscle excitation-contraction coupling (ECC).

Dr. Angela Dulhunty’s research has focussed on the translation of electrical signals in the surface membrane of muscle fibres into the

release of the calcium ions from their internal in the sarcoplasmic reticulum (SR), to enable muscle contraction, i.e. ECC.  In her PhD studies she explored the complex nature of transverse (T-) tubule extensions of the surface membrane which conduct the surface electrical signal throughout the fibre cross-section. The discovery of asymmetric charge movement arising from dihydropyridine receptors in T-tubules allowed her to examine this voltage sensor for ECC in fast and slow-twitch mammalian muscle and to apply this to her subsequent studies of the voltage dependence for ECC. The other major component of ECC, the ryanodine receptor (RYR) calcium release channel in the SR, was identified in the late 1980s. Dulhunty was amongst the first researchers to study single RYR ion channels from skeletal and cardiac muscle using lipid bilayer electrophysiology. She has continued to study RYR channels, combining electrophysiology, biochemistry, protein chemistry, structural biology and molecular biology to explore normal RYR function and pathological changes that reduce skeletal muscle function and which can compromise cardiac muscle to the extent of causing heart attack. 

Alexander Kushnir, MD, PhD - "​​RYR-1 Myopathy Database”

Dr. Alexander Kushnir is a Cardiac Electrophysiology Fellow at Columbia University Medical Center in New York. He received his MD/PhD with distinction from Columbia University. His clinical and research interests are regulation of intracellular calcium in cardiac and skeletal muscle disorders. He has published articles in major medical journals and cardiac electrophysiology textbooks and has multiple research grants.

William R. Lagor, PhD - “Targeted Removal of Pathogenic RYR-1 Alleles”

Dr. William R. Lagor is Assistant Professor of Physiology and Biophysics at Baylor College of Medicine. Dr. Lagor’s research focuses on the genetics of lipid and lipoprotein metabolism. A major goal of Dr. Lagor’s research is to understand how rare and common genetic variation alters metabolic pathways and determines an individual’s susceptibility to disease. His lab uses a combination of gene targeting and viral vectors for gene delivery to investigate the physiology of lipid metabolism in model organisms, and identify potential new therapeutic targets.

Andrew R. Marks, MD - Rycal Treatment in RYR-1-Related Myopathy Muscle Biopsies”

Dr. Andrew R. Marks received his undergraduate degree from Amherst College where he was the first student in the history of the college to graduate with honors in two subjects (Biology and English), and his MD from Harvard Medical School. Following an internship and residency in internal medicine at the Massachusetts General Hospital (MGH), he was a post-doctoral fellow in molecular genetics at Harvard Medical School, and then a clinical cardiology fellow at the MGH. He is board certified in internal medicine and in cardiology. Dr. Marks is Chair and Professor of the Physiology and

Cellular Biophysics Department at Columbia University. From 2002-2007 Dr. Marks was Editor-in-Chief of the Journal of Clinical Investigation. His honors include: ASCI, AAP, the National Academy of Medicine (2004), American Academy of Arts and Sciences (2005) and the National Academy of Sciences (2005). Doctor of Science Honoris Causa from Amherst College (2009), the ASCI Stanley J. Korsmeyer Award (2010), the Pasarow Foundation Award for Cardiovascular Research (2011), the Ellison Medical

Foundation Senior Scholar in Aging Award (2011), Docteur Honoris causa, de l’Université de Montpellier (2016), Glorney-Raisbeck Award from NY Academy of Medicine (2016),  Columbia University Dean’s Award for Excellence in promoting Diversity (2017), the Naranjan Dhalla Award for Innovative Investigators in Cardiovascular Sciences, International Academy of Cardiovascular Sciences (2018). In 2015 Dr. Marks was chosen to present the Ulf von Euler lecture at the Karolinska Institute. Dr. Marks’ identification of the mechanism of action of rapamycin, inhibition of vascular smooth muscle proliferation and migration, lead to the development of the first drug-eluting stent (coated with rapamycin) for treatment of coronary artery disease. This substantially reduced the incidence of in-stent restenosis. In 2014 Dr. Marks reported the high resolution structure of the mammalian type 1 ryanodine receptor/calcium release channel (required for excitation-contraction coupling in skeletal muscle) which he had cloned and worked on to define it’s regulation in health and disease since 1989. His research has contributed new understandings of fundamental mechanisms that control muscle contraction, heart function, lymphocyte activation, and cognitive function. He discovered that “leaky” intracellular calcium release channels (ryanodine receptors) contribute to heart failure, fatal cardiac arrhythmias, impaired exercise capacity in muscular dystrophy, post-traumatic stress disorder (PTSD) and Alzheimer’s Disease. Dr. Marks discovered a new class of small molecules (Rycals), developed in his laboratory, that target leaky ryanodine receptor channels and effectively treat cardiac arrhythmias, heart failure, muscular dystrophy and prevent stress induced cognitive dysfunction and symptoms of Alzheimer’s Disease in pre-clinical studies. Rycals have shown promising results in pilot clinical trials for the treatment of heart failure and cardiac arrhythmias, and are entering clinical trials for the treatment of Duchenne Muscular Dystrophy and RyR-1 myopathy. Dr. Marks is Chair of ARMGO Pharma, Inc., a biotech company focused on developing therapeutics targeting leaky RyR channels.

 

Dr. Marks is Chair of the Scientific Advisory Board (SAB) of the RYR-1 Foundation.

Katy Meilleur, PhD, CRNP - “Rycal Treatment in RYR-1-Related Myopathy Muscle Biopsies”

Dr. Katy Meilleur completed a BS at the University of Maryland in biology and then worked in a genetics lab at the University of Pennsylvania. She then pursued the BSN/MSN program at University of Pennsylvania as a second-degree nursing student. After completing her BSN, she worked as a neonatal intensive care nurse at the Hospital of the University of Pennsylvania (HUP) while finishing her MSN requirement. She completed the MSN program as an acute/chronic pediatric nurse practitioner and worked in the newborn nursery of HUP while attending Johns Hopkins University for her PhD program. 

Her interests in international health and genetics led her to do her dissertation with a neurologist at the National Institutes of Health who had a partnership in Bamako, Mali, West Africa. There she identified a novel genetic locus for a hereditary spastic paraplegia. She also developed a scale to test knowledge and attitudes of Malians before and after receiving genetic testing for the first time. 

After a postdoctoral fellowship in the National Human Genome Research Institute, she became a staff scientist in the National Institute of Neurological Disorders and Stroke and continued to do gene discovery studies and scale development in the pediatric

neuromuscular section. 

She is now an Assistant Clinical Investigator in the intramural program of the National Institute of Nursing Research where she develops and studies clinical outcomes in pediatric neuromuscular disease, with a focus on RYR-1-related myopathies. She is currently performing a clinical trial in RYR-1 using an antioxidant, and her goal is to continue to test therapies for RYR-1-related diseases. 

Filip Van Petegem, PhD - "Structural Investigation of Disease-Associated Mutations in the Ryanodine Receptor Pore and EF Hand Region”

Dr. Filip Van Petegem is Professor at the University of British Columbia (UBC), Department of Biochemistry and Molecular Biology (Vancouver, Canada). Born in Belgium, he obtained his PhD in Biochemistry at Ghent University in 2002 and performed postdoctoral studies at the University of California San Francisco (UCSF).

Dr. Van Petegem leads a research lab at UBC, where he studies the structure and function of ion channels, with a focus on cardiac and skeletal muscle.  This includes the Ryanodine Receptor (RyR) and voltage-gated calcium channels (CaV), two types of ion channels that have intimate communications inside muscle cells. Mutations in the genes that encode these channels cause malignant hyperthermia, central core disease, cardiac arrhythmia, and much more.  A major approach consists of determining very detailed 3D structures of these channels, allowing his lab to peer into the direct effects of the disease mutations on the structure.

Dr. Van Petegem has received New Investigator Awards from the CIHR (2008) and the Michael Smith Foundation for Health Research (2008) as well as a UBC Faculty of Medicine Award for excellence in basic science (2013). He received a new investigator award from the Canadian Society for Molecular Biosciences (CSMB) in 2016, and a Killam Research Fellowship in 2017. He serves on the Macromolecular Beam team committee at the Canadian Light Source and frequently consults with industry.

Dr. Van Petegem is a member of the Scientific Advisory Board (SAB) of the RYR-1 Foundation.

Contact: 

P.O. Box 13312, Pittsburgh, PA 15243

© 2014 by The RYR-1 Foundation. 

Phone:

412-529-1482

The information provided by The RYR-1 Foundation on this site or by any links to this site is for educational purposes only. It should not be interpreted as a recommendation for a specific treatment plan, product, medical, or healthcare provider. Use of this web site does not replace medical consultations with a qualified professional to meet the individual’s needs. In addition, medical information can change rapidly; therefore, some information may be out of date, and/or contain inaccuracies or typographical errors. Ultimately, if you have concerns about your health, particularly RYR-1 related diseases, you should consult your health care provider.