Research Faculty

Address
630 West 168th Street
P&S 10-508
New York, NY 10032


Phone: 212-305-1306
Fax:

hjw14@columbia.edu
Education and Training
Cornell University, 1981, B.A.
University of Chicago, 1985, M.D.
Affiliations
Anatomy & Cell Biology
Liver

Collaborations
With Gregg Gundersen, projects on nucleocytoplamic connections in muscular dystrophy and progeria funded by NIH grants.
With Ron Liem, project on mouse models of Charcot-Marie-Tooth Type 2E disease funded by MDA grant.characterization of mouse models of Emery-Dreifuss muscular dystrophy.

Intl Collaborations
With Sophie Zinn-Justin at Commissariat à l'énergie atomique et aux energies (France) alternatives on structural biology of nuclear envelope proteins
With Antoine Muchir at Institut de Myology (France) on developing treatments for cardiomyopathy and muscular dystrophy caused by nuclear envelope protein gene mutations


Training Activities
Co-director Med into Grad
Co-director Digestive and Liver Diseases (Medicine) T32 grant
Howard J. Worman, M.D.
Professor of Medicine and Pathology and Cell Biology
Research Summary

Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called "laminopathies". While mutations and clinical phenotypes of "laminopathies" have been carefully described, data explaining pathogenic mechanisms are only emerging. Our laboratory is focused on deciphering how mutations in genes encoding nuclear lamins and other nuclear envelope proteins cause disease. In particular, we are discovering alterations in cell signal transduction pathways and gene expression that occur as a result of abnormalities in the nuclear envelope. For example, we have shown that A-type lamin alterations that cause cardiomyopathy lead to abnormally activated MAP kinase activities in heart and that blocking these enzymes can prevent disease in a mouse model. Our long-term goal is to use this information to discover treatments for this the fascinating group of diseases associated with the nuclear envelope. We have also be characterizing nuclear envelope autoantigens in autoimmune liver diseases such a primary biliary cirrhosis and autoimmune hepatitis. In another new research project, we are using inbred strains of mice to attempt to identify susceptibility genes for non-alcoholic steatohepatitis, a liver disease that occurs in some people who are obese.

Service Activities

Dr. Worman is an attending physician in the Liver Clinic at Columbia University Medical Center and also provides second opinion consultation in liver diseases at the faculty practice office of the Division of Digestive and Liver Diseases. He also attends on the General Medicine Service one month each year.
Selected Publications

Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, Bonne G, Worman HJ. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J Clin Invest (2007);117:1282-93.

Worman HJ, Fong LG, Muchir A, Young SG. Laminopathies and the long strange trip from basic cell biology to therapy. J Clin Invest (2009);119:1825-36.

Dauer WT, Worman HJ. The nuclear envelope as a signaling node in development and disease. Dev Cell (2009);17:626-38.

Folker ES, Östlund C, Luxton GW, Worman HJ, Gundersen GG. Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement. Proc Natl Acad Sci U S A (2011);108:131-6.

Choi JC, Muchir A, Wu W, Iwata S, Homma S, Morrow JP, Worman HJ. Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation. Sci Transl Med (2012);4:144ra102.

Shin JY, Méndez-López I, Wang Y, Hays AP, Tanji K, Lefkowitch JH, Schulze PC, Worman HJ, Dauer WT. Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance. Dev Cell (2013);26:591-603.

Gundersen GG, Worman HJ. Nuclear positioning. Cell. (2013);152:1376-89.

Chang W, Folker ES, Worman HJ, Gundersen GG. Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts. Mol Biol Cell (2013);in press.

Current Projects

R01AR048997-10 Worman (PI) 07/01/2009 – 06/30/2014
NIH/NIAMS
Pathogenesis of Emery-Dreifuss Muscular Dystrophy

R01HD070713-03 Gundersen; Worman (MPI) 03/15/2011 – 01/31/16
NIH/NICHD
The Nucleocytoskeleton in Progeria and Aging

No number Worman (PI) 08/15/2013 – 08/14/2015
Los Angeles Cardiovascular and Thoracic Foundation
Research into Use of Selumetinib to Treat LMNA Cadiomyopathy

No number Liem (PI) 01/01/2010 – 04/30/2014
Howard Hughes Medical Institute
Med into Grad Institutional Initiative 2009 Program in Molecular Basis of Health and Disease

MDA255038 Liem (PI) 01/01/2013 – 12/31/2015
Muscular Dystrophy Association
Characterization of a new mouse model for CMT2E

Honors and Awards

Phi Beta Kappa, Cornell University, 1980
Bachelor of Arts cum laude in biology, Cornell University, 1981
Calvin Fentress Research Fellowship Award, University of Chicago, 1984
First Prize Midwest Student Medical Research Forum, 1985
Franklin McLean Award for meritorious medical student research, University of Chicago, 1985
Richard W. Reilly Award for outstanding aptitude in gastroenterology, University of Chicago, 1985
Trainee Award in Clinical Research, American Federation for Clinical Research, 1989
Henry Christian Award, American Federation for Clinical Research, 1990
Charles E. Culpeper Scholar in Medical Science, 1994
SmithKline Beecham Clinical Research Award, American Gastroenterological Association, 1994
Travel Award 16th International Congress of Biochemistry & Molecular Biology New Delhi, American Society For Biochemistry and Molecular Biology, 1994
Silberberg Award, Columbia University College of Physicians and Surgeons, 1995
Irma T. Hirschl Scholar, Irma T. Hirschl Trust, 1997
American Society for Clinical Investigation, 1998
Association of American Physicians, 2010
Committees , Council, and Professional Society Memberships

American Association for the Advancement of Science
American Association for the Study of Liver Diseases
American Chemical Society
American College of Physicians
American Federation for Medical Research
American Gastroenterological Association
American Society for Cell Biology
American Society for Clinical Investigation
New York Academy of Sciences (Vice-Chairman, Section of Biological Sciences, 1992- 1993; Chairman, Section of Biological Sciences, 1993-1994; Advisory Board 1995-1996)
Association of American Physicians
NIH Nucleocytoplasmic Dynamics and Transport Initial Review Group (chartered member 2010-2014)

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