Ronald Cohn, M.D.

Associate Professor
Pediatrics, Neurology and the McKusick-Nathans Institute of Genetic Medicine

Education and Training:

M.D. , University GHS Essen School of Medicine, Germany 1996
Combined Pediatric/Clinical Genetic Residency, Johns Hopkins University, 2006

Main interests:

Research in my laboratory focuses on the biology of muscle regeneration as it relates to various inherited and acquired myopathic states.  Satellite cells are stem-cell like cells which reside in skeletal muscle and are the main resource of repairing damaged skeletal muscle whether inflicted by trauma or genetic disorders.  We are using a variety of animal models to study the relationship between impaired muscle regeneration and myopathic disease progression.  It is our goal to characterize biological pathways which are crucial for satellite cell function.  Ultimately, identification of these pathways will lead to the development of novel therapeutic strategies.  We are also interested in the molecular pathogenesis of cardiomyopathies associated with muscular dystrophies.  One focus has been to characterize altered signaling pathways in cardiac muscle which are amenable to pharmacological treatment.

Using a novel approach to understanding the mechanisms of maintaining muscle mass and regeneration, we have started to work with hibernating ground squirrels.  Maintenance of normal muscle mass and physiology is essential for health.  Disuse (e.g., immobilization, denervation, and microgravity) and aging result in debilitating loss of skeletal muscle.  Loss of muscle mass is thought to be the net result of a decrease in satellite cell number and/or impaired proliferation, associated with increased muscle proteolysis and decreased protein synthesis.  In stark contrast to the above, hibernating mammals have evolved mechanisms to survive prolonged immobility without pathologic loss/atrophy of muscle mass.   The molecular mechanisms underlying this fascinating phenomenon are largely unknown.   We are currently for the first time applying knowledge of normal mechanisms of muscle protection in the hibernating mammal to the disease process of disuse muscle atrophy in non-hibernating mammals.  This will provide unique insights into the fundamental cellular and molecular pathways underlying skeletal muscle atrophy and the protection against it.

In addition, we are interested in studying the molecular mechanisms underlying hypotonia and muscle weakness in genetically characterized mouse models of various disease entities.  Hypotonia (decreased muscle tone) is a symptom of over 500 different genetic disorders.  We have recently launched the Johns Hopkins Center for Hypotonia.  The center focuses on identifying, supporting and treating patients with various conditions associated with hypotonia.  Our goal is to directly combine our clinical experience with our basic research efforts to ensure that the clinical approach to and therapy for the patient will be tailored to his/her individual needs.

Research Interests:

• Molecular mechanisms of muscle regeneration in various inherited and acquired myopathic states
• Molecular pathogenesis of cardiomyopathies associated with muscular dystrophy
• Molecular mechanisms of hypotonia and muscle weakness in genetically characterized mouse models of various disease entities
• Molecular mechanism underlying the maintenance of skeletal muscle during hibernation

Clinical Activities:

The Johns Hopkins Center for Hypotonia
To schedule and appointment contact: 

Maria Johnson, MS, CGC
410-955-3071

Educational Activities:

• Director, Medical Genetics Residency Training Program
• Preceptor, Predoctoral Training Program in Human Genetics

Recognition and Leadership Roles:

• University of Duesseldorf, Germany, Doctoral Thesis honored with “cum laude”
• Postdoctoral Research Grant, German Research Foundation, DFG
• Poster Award for Research of Highest Caliber; University of Iowa College of Medicine Research Week
• David M. Kamsler Award for Outstanding Compassionate and Expert Care of Pediatric Patients by the Johns Hopkins Children’s Center Staff
• Award for Best Postdoctoral Research at the 2nd Annual Retreat of the McKusick-Nathans Institute of Genetic Medicine
• Young Investigator Award at the 7^th International Symposium on the Marfan syndrome, Ghent, Belgium, September 2005
• Johns Hopkins Clinician Scientist Award
• The Helen B. Taussig Award, Johns Hopkins Young Investigators’ Day
• First Annual Harvard-Partners Center for Genetics and Genomics Award in Medical Genetics
• Mentored Clinical Investigator Career Development Awards in Muscle Disease Research (KO8)

Selected Publications:

Flanigan KM, Kerrl, Bromberg MB, Leonard C, Tsuruda J, Zhang P, Gonzalez-Gomez I, Cohn RD, Campbell KP and Leppert M. Congenital muscular dystrophy with rigid spine syndrome: a clinical, pathological, radiological, and genetic study. Ann Neurol 2000;47:152-161.

Franz WM, Mueller M, Herrmann R, Frey N, Cohn RD, Voit T, Katus HA. Association of nonsense mutation of dystrophin with disruption of sarcoglycan complex in X-linked dilated cardiomyopathy. Lancet 2000;355:1781-1785

Cohn RD and Campbell KP.  The molecular basis of muscular dystrophy.  Muscle and Nerve 2000;23:1456-1471

Cohn RD and Campbell KP.  Pathogenetic role of the sarcoglycan-sarcospan complex in cardiomyopathies.  Acta Myologica 2000;19:171-180

Voit T, Kutz P, Leube B, Neuen-Jacob E, Schroeder JM, Cavallotti D. Vaccario ML, Schaper J, Broich P, Cohn RD, Baethmann M, Gohlich-Ratmann G, Scopetta C, Herrmann R.  Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus.  Neuromuscul Disord. 2001;11:11-19.

Cohn RD, Durbeej M, Moore SA, Prouty S, Coral-Vasquez R, Campbell KP.  Prevention of the cardiomyopathic phenotype in genetic mouse models with absence of the smooth muscle sarcoglycan complex. J Clin. Invest. 2001;107:R1-R7

Voit T, Kutz P, Leube B, Neuen-Jacob B, Schroder JM, Cavalotti D, Vaccario ML, Schaper J, Broich P, Cohn RD, Baethmann M, Gohlich-Rathmann G, Scopetta C, Herrmann R.  Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus.  Neuromusc. Disord. 2001;11:11-19

Michele DE, Barresi R, Kanagawa M, Saito F, Cohn RD, Satz JS, Dollar J, Nishino I, Kelley RI, Somer H, Straub V, Mathews KD, Moore SA, Campbell KP. Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies.  Nature 2002;418:418-421

Moore SA, Saito F, Chen J, Michele DE, Henry MD, Messing A, Cohn, RD, Ross-Barta SE, Westra S, Williamson RA, Hoshi T, Campbell KP.  Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy.  Nature 2002;418:422-425

Cohn RD , Henry MD, Michele DE, Barresi R, Saito F, Moore SA, Flanagan JD, Swarchuk MW, Robbins ME, Mendell JR, Williamson R, Campbell KP.  Disruption of Dag1 in Differentiated Skeletal Muscle Reveals a Role for Dystroglycan in Muscle Regeneration.  Cell 2002;110:639-648

Saito F, Moore SA, Barresi R, Henry MD, Messing A, Ross-Barta SE, Cohn RD, Williamson RA, Sluka KA, Sherman DL, Brophy PJ, Schmelzer JD, Low PA, Wrabetz L, Fletri ML, Campbell KP.   Unique Role of Dystroglycan in Peripheral Nerve Myelination, Nodal Structure and Sodium Channel Stabilization. Neuron 2003;38:747-758

Cohn RD and Campbell KP.  Pathogenesis of cardiomyopathy associated with muscular dystrophy.  Chapter 12 in Chien KR. “Molecular basis of cardiovascular disease) 2004;306-310

Cohn RD. Muscle Brain Diseases. In Singer/Crawford/Kossof/Hartmann. “Treatment of Pediatric Neurologic Diseases” 2004

Barresi F, Michele DE, Kanagawa M, Harper HA, Dovico SA, Satz, JS, Moore SA, Zhang W, Schachter H, Dumanski JP, Cohn RD, Nishino I Campbell KP.  LARGE can functionally bypass ?-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nature Medicine 2004;10:696-703

Cohn RD. Invited Review: Dystroglycan: Important player in skeletal muscle and beyond.  Neuromusc Disord 2005;15:207-217

Habashi HP, Judge DP, Holm TM, Cohn RD, Loeys BL, CooperTK, MyersL, Klein EC, LiuG, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome Science 2006;312:117-121

Peddy SB, Vricella LA, Crosson JE, Oswald GL, Cohn RD, Halushka MK, Cameron DE, Valle D, Loeys BL.  Infantile restrictive cardiomyopathy due to a mutation in cardiac troponin T gene.  Pediatrics, 2006;117:1830-1833

Cohn RD, Eklund E,  Bergner AL, Casella JF, Woods SL, Althaus J, Blakemore KJ, Fox HE, Hoover-Fong JE, Hamosh A, Braverman NE, Freeze HH Boyadjiev SA. Intracranial Hemorrhage as the Initial Manifestation of a Congenital Disorder of Glycosylation.  Pediatrics 2006;118:e514-521

Cohn RD, Habashi JP, Loeys BL, Klein EC, Holm TM, Judge DP, Dietz HC.  Angiotensin II type 1 receptor blockade prevents TGFb-induced failure of muscle regeneration in multiple myopathic states. Submitted

Cohn RD, Liang HY, Shetty R, Abraham T, Wagner KR. Myostatin Does not Function as a Major Inhibitory Factor in Cardiac Muscle Growth and Regeneration.  Neuromuscular Disord. 2007;17:290-296

Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome.  Science 2006;312:117-121

Cohn RD, van Erp C, Habashi JP, Soleimani AA, Klein EC, Lisi MT,  Gamrad M, Loeys BL,  Holm TM, Judge DP, Ward CW, Dietz HC.  Angiotensin II type 1 receptor blockade attenuates TGFb-induced failure of muscle regeneration in multiple myopathic states.  Nature Medicine 2007;13:204-210

Contact:

Ron Cohn, MD

McKusick-Nathans Institute of Genetic Medicine
Johns Hopkins University School of Medicine
Broadway Research Building
733 Nth Broadway
Room 529
Baltimore MD 21205
(410) 955-3071

E-mail: rcohn2@jhmi.edu