Howard J. Worman, MD

Board Certifications: 
Internal Medicine
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Overview

Areas of Expertise / Conditions Treated

Liver Disease, Internal Medicine

Academic Appointments

  • Professor of Medicine
  • Professor of Pathology & Cell Biology

Howard J. Worman, M.D. is Professor of Medicine and Pathology and Cell Biology at Columbia University’s College of Physicians and Surgeons. Dr. Worman received his BA from Cornell University and MD from the University of Chicago Pritzker School of Medicine. He did clinical training in internal medicine at New York Hospital-Cornell Medical Center and postdoctoral research training in cell biology at Rockefeller University. He then obtained clinical training in liver diseases at the Mount Sinai Medical Center.

Dr. Worman is internationally recognized for his research in cell biology and hepatology. His laboratory research is focused on primarily on the cell biology of rare genetic diseases. These include different types of muscular dystrophy, cardiomyopathy, lipodystrophy and premature aging syndromes (progeria) . He also does research on non-alcoholic fatty liver disease and on the characterization of antibodies in autoimmune liver diseases. His clinical practice is primarily devoted to consultation in liver diseases.

Dr. Worman is an author on over 200 scientific publications. In 1998, he was elected to membership in the American Society for Clinical Investigator and, in 2010, to the Association of American Physicians. He has served on the Editorial Boards of Hepatology, Gastroenterology, Molecular Biology of the Cell and Journal of Autoimmunity and as a Section Editor of BMC Cell Biology. Dr. Worman is also author of the popular Liver Disorders and Hepatitis Sourcebook (McGraw-Hill, 2006).

Email: hjw14@cumc.columbia.edu

Hospital Affiliations

  • NewYork-Presbyterian/Columbia

Gender

  • Male

Credentials & Experience

Education & Training

  • Pritzker School of Medicine at the University of Chicago
  • Internship: New York Hospital - Cornell Medical Center
  • Residency: New York Hospital-Cornell Medical Center
  • Fellowship: New York Hospital-Cornell Medical Center
  • Fellowship: Rockefeller University

Board Certifications

  • Internal Medicine

Honors & 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

Research

I trained in cell biology and as an internist. My major research focus has been on the nuclear lamina and nuclear envelope. In 1993, my group characterized LMNA, the gene encoding the A-type nuclear lamins, mutations in which cause a broad range of diseases often called laminopathies. These include cardiomyopathy, muscular dystrophy, Hutchinson-Gilford progeria syndrome and Dunnigan-type familial partial lipodystrophy. These discoveries have led to my developing expertise in molecular genetics and genomic medicine, including mutation calling from human genome sequences and phenotype-genotype analyses in humans with inherited diseases. I have also generated and used numerous mouse models of human disease to dissect pathogenic mechanisms. In addition to extensive research using mouse models of diseases caused by LMNA mutations, my laboratory has performed genome-wide association studies in mice to identify genes that influence liver phenotypes.

We have also generated novel models of nonalcoholic steatohepatitis by deleting genes encoding interacting nuclear envelope and endoplasmic reticulum proteins from mouse hepatocytes. In addition to my basic research, I have been active in the nuclear envelope research field by serving on the NIH Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section and the NIH Action Plan for the Muscular Dystrophies Mechanisms of Muscular Dystrophy Working Group Section on myopathies caused by mutations on genes encoding nuclear envelope proteins. I also serve on the Scientific Advisory Board of MNG Laboratories, which provides human diagnostics services, including Next Generation Sequencing. My overall goal is to better integrate cell biological approaches into precision medicine and genomics research.

Research Interests

  • How mutations in genes encoding proteins of inner nuclear membrane cause inherited diseases
  • Liver diseases, including fatty liver disease and autoimmune liver diseases.

Grants

2R01AR048997 Worman (PI) 07/01/2002 - 06/30/2020
NIH/NIAMS: Pathogenesis of Emery-Dreifuss Muscular Dystrophy
The goals of this project are to examine the interaction between A-type lamins, emerin and LAP1 using genetic approaches in mice and biochemical and biophysical approaches in cells, to examine the binding of A-type lamins to ERK1/2 and to test how DUSP4 links activation of ERK1/2 to pathology in Emery-Dreifuss muscular dystrophy.

1R01AR068636-01 Worman; Gundersen (MPI) 09/01/2015 - 06/30/2020
NIH/NIAMS: Nuclear Movement LINC Complex and Emery-Dreifuss Muscular Dystrophy
The goal of this project is to test the hypothesis that in Emery-Dreifuss muscular dystrophy there is a link between defective nuclear movement and ERK1/2 activity in myoblasts and muscle fibers and to examine the movement of nuclei and migration of myoblasts in cells with disease-causing mutations.

5R01HD070713-04 Gundersen; Worman (MPI) 03/15/2011 - 01/31/2016
NIH/NICHD: The Nucleocytoskeleton in Progeria and Aging
The goal of this project is to determine how abnormalities in the nuclear lamina in Hutchinson-Gilford progeria syndrome and cause abnormalities in nuclear migration and in the dynamics of nuclear envelope proteins that link the nucleus to the cytoskeleton and relate this to physiological aging.  Dr. Worman shares the direct costs on this MPI grant with the other PI, Dr. Gundersen.

MDA 294537 Worman (PI) 05/01/2014 - 04/30/2017
Muscular Dystrophy Association: Emerin-LAP1 Interaction and X-linked Emery-Dreifuss Muscular Dystrophy
The goals of this project are to determine the smallest interacting domains of LAP1 and emerin and examine their interaction in transfected cells using fluorescence photobleaching methods, examine the effects of emerin and LAP1 depletion on AKT and ERK1/2 signaling and determine if pharmacological inhibition of ERK1/2 signaling and mTOR activity improve muscle function in mice lacking emerin and LAP1 from muscle.

NUCLEOSKELETON-CYTOSKELETON CONNECTIONS AND CELL POLARITY IN AGING (Federal Gov)

Aug 1 2019 - Apr 30 2024

NUCLEAR ENVELOPE, LIPOPROTEIN METABOLISM, AND HEPATIC STEATOSIS (Federal Gov)

Apr 10 2019 - Mar 31 2023

RYANODINE RECEPTOR DEFECTS IN CARDIOMYOPATHY CAUSED BY LAMIN A/C GENE MUTATIONS (Federal Gov)

Apr 4 2019 - Mar 31 2023

X-LINKED EMERY-DREIFUSS MUSCULAR DYSTROPHY (Private)

Jul 11 2019 - Jul 10 2022

EDMD REGISTRY AND DATABASE (Private)

Jul 1 2016 - Jun 30 2021

LAMINOPATHIES AND MTORC1 (Private)

Apr 4 2019 - Mar 3 2021

ROLE OF PERMANENTLY FARNESYLATED PRELAMIN IN THE CARDIOVASCULAR DISEASE OF AGING (Federal Gov)

May 1 2018 - Apr 30 2020

PATHOGENIC ROLE OF SELECTED CARDIAC MYOCYTE- AND FIBROBLAST-SPECIFIC EPIGENETIC CHANGES IN LAMINOPATHIES (Federal Gov)

Mar 15 2016 - Feb 28 2020

EMERIN-LAP 1 INTERACTION AND X-LINKED EMERY DREIFUSS MUSCULAR DYSTROPHY (Private)

May 1 2014 - Apr 30 2017

NUCLEOYTOPLASMIC INTERACTIONS AND DYNAMICS IN EMERY-DREIFUSS MUSCULAR DYSTROPHY (Federal Gov)

Sep 1 2007 - Jun 30 2016

THE NUCLEOCYTOSKELETON IN PROGERIA AND AGING (Federal Gov)

Mar 15 2011 - Jan 31 2016

DUSP4 IN THE PATHOGENESIS OF LMNA CARDIOMYOPATHY (Federal Gov)

Aug 1 2013 - Oct 31 2015

USE OF SELUMETINIB TO TREAT LMNA CARDIOMYOPATH (Private)

Aug 1 2013 - Jul 31 2015

TREATMENT OF INHERITED AND GENETIC CARDIOMYOPATHIES BY ERK OR JNK INHIBITION (Private)

Jun 28 2013 - Dec 27 2014

PRECLINICAL DEVELOPMENT OF NOVEL MED1/2 INHIBITORS TO TREAT INHERITED CARDIOMYOPA (Federal Gov)

Sep 1 2013 - Aug 31 2014

TRAINING PROGRAM IN MOLECULAR BASIS OF HEALTH AND DISEASE (Private)

Apr 1 2010 - Mar 31 2014

THERAPIES FOR INTERMEDIATE FILAMENT DISEASES (Private)

Jan 1 2012 - Dec 31 2013

LAP1 INVOLVEMENT IN THE PATHOLOGY OF EMERGY-DREIFUSS MASCULA R DYSTROPHY (Private)

Jul 1 2010 - Jun 30 2013

TREATMENT OF CARDIOMYOPATHY IN (Private)

Jul 1 2010 - Jun 30 2013

AGREEMENT FOR COLLABORATION SERVICES (Private)

Jan 1 2010 - Jun 30 2013

MOLECULAR AND CELLULAR PATHOGENSIS OF EMERY-DREIFUSS MUSCULA (Federal Gov)

Feb 1 2010 - Jan 31 2013

IDENTIFICATION OF COMPOUNDS TO TREAT CHARCOT-MARIE-TOOTH TYP E 2E NEUROPATHY (Federal Gov)

Jul 1 2009 - Aug 31 2012

MAP KINASE SIGNALING INHIBITORS TO TREAT CARDIOMYOPATHY (Private)

Apr 23 2010 - Apr 22 2012

HUMAN MONOCLONAL ANTI-BODY PROJECT (Private)

Oct 20 2006 - Jun 30 2011

Selected Publications

Shin JY, Hernandez-Ono A, Fedotova T, Östlund C, Lee MJ, Gibeley SB, Liang CC, Dauer WT, Ginsberg HN, Worman HJ. Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis. J Clin Invest. 2019 Aug 13;130:4885-4900. PMID: 31408437

Worman HJ, Michaelis S. Permanently Farnesylated Prelamin A, Progeria, and Atherosclerosis. Circulation. 2018; 138(3):283-286. PMID: 30012702

Wang Y, Lichter-Konecki U, Anyane-Yeboa K, Shaw JE, Lu JT, Östlund C, Shin JY, Clark LN, Gundersen GG, Nagy PL, Worman HJ. A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder. J Cell Sci. 2016; 129(10):1975-80 PMID:27034136

Selected Reviews and Books

Gundersen GG, Worman HJ. Nuclear positioning. Cell 2013;152:1376-1389

Worman HJ. Nuclear lamins and laminopathies. J Pathol 2012;226:316-325

Worman HJ, Ostlund C, Wang Y. Diseases of the nuclear envelope. Cold Spring Harb Perspect Biol 2010;2:a000760.

Dauer WT, Worman HJ. The nuclear envelope as a signaling node in development and disease. Dev Cell 2009;17:626-638

Worman HJ. Nuclear envelope autoantigens in primary biliary cirrhosis. Hepatol Res 2007;37 Suppl 3:S406-S411

Worman HJ. The Liver Disroders Sourcebook McGraw-Hill (2006)