Harry (Hal) Dietz, M.D.

Education:

B.S., Duke University, 1980
M.D., SUNY Upstate Medical Center, 1984
Resident in Pediatrics, Johns Hopkins Hospital, 1984-1987
Fellow in Cardiology, Johns Hopkins Hospital, 1988
Postdoc, The Johns Hopkins University, 1989

Main Interests:

Our laboratory is interested in the development and homeostasis of the arterial wall. One goal is to understand genetic factors that predispose to aortic aneurysm, a condition accounting for 1-2 percent of deaths in industrialized countries. Our initial approach has been to study Marfan syndrome (MFS), a genetic disease that includes aortic aneurysm as part of the condition and that is caused by mutations in a single gene. It is anticipated that a comprehensive understanding of the cause, progression, and modulation of MFS will promote a greater understanding of vascular wall biology. Other vascular disorders currently being studied include: familial tetralogy of Fallot, cerebral cavernous malformation, a novel dominant syndrome of premature aging that prominently includes the cardiovascular system, the association of bicuspid aortic valve with aneurysm, and a novel and aggressive aneurysm phenotype called Loeys-Dietz syndrome. During our study of MFS, we recognized that a particular type of mutation is associated with very low levels of mutant RNA and tends to cause very mild forms of the disease. A second major interest of our laboratory is to understand the mechanism of nonsense-mediated mRNA decay; to evaluate its basic biologic purpose; and to assess its role as a potent modulator of disease severity in a wide variety of genetic disorders.
 

Research Interests:

• Pathogenesis of Marfan syndrome
• Molecular basis of inherited disorders of vascular development and homeostasis
• Genetics of aging
• Nonsense-mediated mRNA decay
• Link: National Marfan Foundation  

Clinical Activities:

• Board Certification: Board Certified in Pediatrics
• Clinical Interests: Marfan syndrome, connective tissue disorders, and cardiovascular genetics
• Clinic:
  
  Medical Genetics Clinic
  Johns Hopkins Outpatient Center (JHOC)
  8th floor, Pediatric Specialty Clinics area
  601 North Caroline Street
  Baltimore, MD 21287
  Phone: 410-955-3071 Fax: 410-614-9246  

Educational Activities:

• Preceptor and Assistant Director, Predoctoral Training Program in Human Genetics
• Preceptor and Assistant Director, Medical Genetics Training Program
• Preceptor, Biochemistry and Molecular Biology Training Program
• Preceptor, Cellular and Molecular Medicine Training Program
• Director of the Professional Advisory Board, National Marfan Foundation

Recognition and Leadership Roles:

• Richard Starr Ross Research Scholar, JHMI
• Richard D. Rowe Award for outstanding research in Pediatric Cardiology
• Young Investigator Award, Society for Pediatric Research
• Antoine Marfan Award, National Marfan Foundation
• Howard Hughes Medical Institute 
• Board of Governors, National Human Genome Research Institute
• American Society for Pediatric Research
• American Society for Clinical Investigation

Selected Publications:

1. Noensie F and Dietz HC.  A strategy for disease gene identification through nonsense-mediated mRNA decay inhibition.  Nature Biotechnology 19:434-439, 2001.

2. Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC.  Association of human aging with functional variant of klotho.  PNAS 99:856-861, 2002.

3. Frischmeyer PA, van Hoof A, O’Donnell K, Guerrerio AL, Parker R, Dietz HC.  An mRNA surveillance mechanism that eliminates transcripts lacking termination codons.  Science 295(5563):2258-61, 2002.

4. Mendell JT, ap Rhys CMJ, Dietz HC.  Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts.  Science 298:419-422, 2002.

5. Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC.  Dysregulation of TGF-ß activation contributes to pathogenesis of Marfan syndrome.  Nature Genet  33(3):407-411, 2003.

6. Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC.  KLOTHO Allele Status and the Risk for Early-Onset Occult Coronary Artery Disease. Am J Hum Genet 72:1154-1161, 2003.

7. Judge DP, Biery NJ, Keene DR, Geubtner J, Myers L, Huso DL, Sakai LY, Dietz HC.  Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome.  J Clin Invest 114:172-81, 2004.

8. Mendell JT, Sharifi NA, Meyer JL, Martinez-Murillo F, Dietz HC.  Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise.  Nature Genet Oct;36(10:1073-8. Epub 2004 Sep 26.  Erratum: Nov;36(11):1238 2004.

9. Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JMW, Mecham RP, Judge DP, Dietz HC.  TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome.  J Clin Invest 114(11):1586-1592, 2004.

10. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu L, Myers LA, De Backer J, Hellermans J, Chen Y, Davis EC, Webb CL, Kress W, Spevak PJ, Cameron DE, Coucke P, Rifkin DB, De Paepe, Dietz HC.  A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGF beta R1 or TGF beta R2.  Nature Genet (released online 1/30/05).

Contact Information:

Harry (Hal) Dietz, MD

Johns Hopkins University School of Medicine
Institute of Genetic Medicine
733 N Broadway
Edward D. Miller Research Building, Room 539
Baltimore, MD  21205

E-Mail: hdietz@jhmi.edu

Academic Assistant

Debbie Churchill
Howard Hughes Medical Institute
Johns Hopkins University School of Medicine
733 N. Broadway
Edward D. Miller Research Building  535
Baltimore, MD  21205
Academic Office: 410-614-5939
Clinic Appointment: 410-955-3071 (option #1)
Fax: 410-614-2256

dchurch4@jhu.edu