Professor, Departments of Pediatrics and Molecular and Human Genetics
Chief, Pediatric Cardiology
Co-Director, Cardiovascular Genetics Clinic

B.S., University of Cincinnati, 1974
M.S., University of Cincinnati, 1977
M.D., University of Cincinnati, 1982
Resident in Pediatrics, Children's Hospital Medical Center, Cincinnati, 1985
Fellow in Pediatric Cardiology, Baylor College of Medicine, 1989

RESEARCH INTERESTS:
As a pediatric molecular cardiologist with clinical involvement in cardiomyopathy, cardiac transplantation, and cardiovascular genetics, my research interests are concerned with genetic and acquired myocardial disease, causes of sudden cardiac death, as well as genetic causes of congenital heart disease with or without associated clinical syndromes. The goal of my laboratory (The Phoebe Willingham Muzzy Pediatric Molecular Cardiology Laboratory) is to map, isolate, and characterize the genes responsible for familial cardiomyopathies in humans and in animal models, arrhythmia syndromes including Brugada syndrome and the long QT syndrome (LQTS), and congenital heart diseases, such as left heart obstructive disorders. Additionally, we have developed a molecular diagnostic approach to viral myocarditis.

X-linked cardiomyopathy was first shown by our laboratory to be caused by dystrophin mutations. More recently, we identified mutations in the dystrophin-associated protein genes d-sarcoglycan and a-dystrobrevin as causes of autosomal dominant dilated cardiomyopathy and LV noncompaction, respectively. We are currently studying many families with familial dilated cardiomyopathy, familial LV noncompaction, familial restrictive cardiomyopathy, and arrhythmogenic RV dysplasia for the causative genes.

Myocarditis is generally caused by viral infection of the heart, leading to acute cardiac decompensation. The diagnosis is presently made histologically via cardiac biopsy but has both a high false negative and false positive rate. Molecular diagnosis of viral genome in cardiac biopsy samples is presently being studied and is expected to provide improved diagnostic capability and potentially improved therapy. In the past, coxsackieviruses have been considered the major cause of disease.Thus far, approximately 500 samples have been analyzed using seven viral PCR primer sets, allowing for specific viral diagnosis, leading to identification of other important viruses causing myocarditis. The tests are now offered as a diagnostic service by the John Welsh Cardiovascular Diagnostic Laboratory.

Approximately 35 percent of cases have been found to be PCR-positive, with adenovirus the most common etiologic agent and the enteroviruses (including Coxsackie) second in frequency. We have made similar findings in patients with heart transplants, associated with rejection. Detailed analysis of the mechanism of adenoviral pathogenesis is underway.

Cardiac arrhythmias are commonly familial, particularly in long QT syndrome and Brugada syndrome. Mutations in multiple ion channel genes have been identified by our group and others. We currently are evaluating families for mutations in novel genes in patients with these disorders, as well as in other arrhythmia disorders.

Finally, the genetic basis of congenital heart diseases is under evaluation. In particular, left heart obstructions are being studied, as are several disorders of the right side of the heart. We anticipate the identification of several new genes coming from these studies.

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SELECTED PUBLICATIONS:
1. Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ, Thiene G (2004). Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs. A New Animal Model of Human Disease. Circulation 109: 1180-1185.

2. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss H-P, McCarthy R, Hare J, Bricker JT, Bowles KR, Towbin JA (2003). Detection of viruses in myocardial tissues by polymerase chain reaction: Evidence of adenovirus as a common cause of myocarditis in children and adults. J. Am. Coll. Cardiol. 42: 466-472.

3. Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin J-H, Vu T, Zhou Q, Bowles KR, DiLenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA (2003). Mutations in Cypher/ZASP in Patients with Dilated Cardiomyopathy and Left Ventricular Non-Compaction. J. Am. Coll. Cardiol. 42: 2014-2027.

4. Vatta M, Stetson SJ, Torre-Amione G, Pauschinger M, Bowles NE, Towbin JA (2002). Selective disruption of the N-terminus of dystrophin in end-stage cardiomyopathies: A final common pathway of cardiac dysfunction. Lancet 359: 936-941.

5. Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, Nademanee K, Brugada R, Brugada J, Veerakul G, Li H, Bowles NE, Brugada P, Antzelevitch C, Towbin JA (2002). Genetic and Biophysical Basis of Sudden Unexplained Nocturnal Death Syndrome (SUNDS), a Disease Allelic to Brugada Syndrome. Hum. Mol. Genet. 11: 337-345.

6. Feng J, Yan JY, Buzin CH, Sommer SS, Towbin JA (2002). Comprehensive Mutation Scanning of the Dystrophin Gene in Patients with Nonsyndromic X-Linked Dilated Cardiomyopathy. J. Am. Coll. Cardiol. 40: 1120-1124.

7. Towbin JA, Bowles NE (2002). The Failing Heart. Nature 415: 227-233.

8. Towbin JA, Bowles NE (2001). Sarcoglycan, The Heart, and Skeletal Muscles: New Treatment Old Drug? J. Clin. Invest. 107: 153-154.

9. Shirali GS, Ni J, Chinnock RE, Vander Dussen LK, Johnson JK, Bowles NB, Towbin JA (2001). Association of Viral Genome with Transplant Coronary Arteriopathy and Graft Loss in Children Following Cardiac Transplantation: Identification Using PCR. N. Engl. J. Med. 344: 1498-1503, 1545-1547.

For more publications, see listing on Pub Med.

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Telephone: 832-826-5651
Fax: 832-925-5921
E-mail:

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