Research Topics
| Howard WormanSummaryAffiliation: Columbia University Country: USA Publications
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Publications
Nucleocytoplasmic connections and deafnessHoward J Worman
Department of Medicine, College of Physician and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA
J Clin Invest 123:553-5. 2013..These results link improper nuclear positioning specifically to the death of outer hair cells in the organ of Corti and ultimately to deafness...- Altered protein dynamics of disease-associated lamin A mutantsSusan Gilchrist
MRC Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, UK
BMC Cell Biol 5:46. 2004..To investigate this we have used photobleaching in human cells to analyse the dynamics of wild-type and mutant lamin A protein at the nuclear periphery... - Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stressMauro Paradisi
VII Divisione, Dermatologia Pediatrica, Istituto Dermopatico dell Immacolata IRCCS, Rome, Italy
BMC Cell Biol 6:27. 2005..The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein... 
Inner nuclear membrane and regulation of Smad-mediated signalingHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10th Floor, Room 508, New York, NY 10032, USA
Biochim Biophys Acta 1761:626-31. 2006..These data demonstrate that proteins within and associated with the inner nuclear membrane lipid bilayer regulate signal transduction pathways involved in numerous developmental, physiological and pathophysiological processes...- The nuclear lamina and inherited diseaseHoward J Worman
Dept of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Trends Cell Biol 12:591-8. 2002..Although the precise pathogenic mechanisms are currently unknown, the involvement of lamins in several different disorders shows that research on the nuclear lamina will shed light on common human pathologies... - Laminopathies and the long strange trip from basic cell biology to therapyHoward J Worman
Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
J Clin Invest 119:1825-36. 2009..Here, we review the laminopathies and the long strange trip from basic cell biology to therapeutic approaches for these diseases... - Here come the SUNs: a nucleocytoskeletal missing linkHoward J Worman
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Trends Cell Biol 16:67-9. 2006..These discoveries have implications for nuclear positioning, nuclear migration and pathogenesis of inherited diseases that are caused by mutations in nuclear envelope proteins... - Inner nuclear membrane and signal transductionHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Cell Biochem 96:1185-92. 2005..In most instances, the mechanisms by which mutations in inner nuclear membrane proteins cause disease are not understood. In at least one case, however, an alteration in signal transduction appears to underlie disease pathogenesis... - How do mutations in lamins A and C cause disease?Howard J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Clin Invest 113:349-51. 2004.... - Prenylated prelamin A interacts with Narf, a novel nuclear proteinR M Barton
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 274:30008-18. 1999..The prenyl-dependent binding of Narf to prelamin A is an important first step in understanding the functional significance of the lamin A precursor... 
The nuclear envelope from basic biology to therapyHoward J Worman
Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Biochem Soc Trans 38:253-6. 2010..However, what became clear is that the nuclear envelope is a cellular structure with critical functions in addition to its traditional role as a barrier separating the nuclear and cytoplasmic compartments in interphase eukaryotic cells...- Nuclear lamins and laminopathiesHoward J Worman
Departments of Medicine and of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, USA
J Pathol 226:316-25. 2012..Despite the incomplete understanding of pathogenic mechanisms underlying the laminopathies, basic research in cellular and small animal models has produced promising leads for treatments of these rare diseases... - Molecular biological methods in diagnosis and treatment of liver diseasesH J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Clin Chem 43:1476-86. 1997..Gene therapy and nucleic acid-based therapeutics are also realistic future treatment options for individuals with liver diseases... - "Laminopathies": a wide spectrum of human diseasesHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Exp Cell Res 313:2121-33. 2007..Future investigations will likely identify new "laminopathies" and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies... - Diseases of the nuclear envelopeHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Cold Spring Harb Perspect Biol 2:a000760. 2010..Studies of these so-called laminopathies or nuclear envelopathies, some of which phenocopy common human disorders, are providing clues about functions of the nuclear envelope and insights into disease pathogenesis and human aging... - MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerinF Lin
Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 275:4840-7. 2000..The LEM module is also present in two proteins of Caenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization... - Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophyC Ostlund
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
J Cell Sci 114:4435-45. 2001..These results indicate that some lamin A mutants causing disease can be aberrantly localized, partially disrupt the endogenous lamina and alter emerin localization, whereas others localize normally in transfected cells... - Protein-protein interactions between human nuclear lamins expressed in yeastQ Ye
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Exp Cell Res 219:292-8. 1995..The results show that the yeast two-hybrid system can be used to study the interactions between structural proteins and their domains... - Primary structure analysis and lamin B and DNA binding of human LBR, an integral protein of the nuclear envelope inner membraneQ Ye
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
J Biol Chem 269:11306-11. 1994..These results demonstrate that LBR is conserved among vertebrate species and that its nucleoplasmic domain can potentially mediate the interaction of both the nuclear lamina and the chromatin with the inner nuclear membrane... - Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membraneE Schuler
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
J Biol Chem 269:11312-7. 1994..These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution... - Structural organization of the human gene encoding nuclear lamin A and nuclear lamin CF Lin
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
J Biol Chem 268:16321-6. 1993..Analysis of the intron positions in these genes supports the hypothesis that the nuclear lamins and other intermediate filament proteins arose from a common ancestor... - Differentiation of antineutrophil nuclear antibodies in inflammatory bowel and autoimmune liver diseases from antineutrophil cytoplasmic antibodies (p-ANCA) using immunofluorescence microscopyB Terjung
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA
Clin Exp Immunol 126:37-46. 2001.... - The inner nuclear membraneH J Worman
Department of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
J Membr Biol 177:1-11. 2000 - Expression of nuclear lamins in human tissues and cancer cell lines and transcription from the promoters of the lamin A/C and B1 genesF Lin
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Exp Cell Res 236:378-84. 1997.... - Hepatitis C virus core protein binds to a DEAD box RNA helicaseN Mamiya
Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 274:15751-6. 1999..These findings demonstrate an interaction between HCV core protein and a host cell protein involved in RNA translation and suggest a mechanism by which HCV may inhibit host cell mRNA translation... - Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBRQ Ye
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 272:14983-9. 1997..The modular domain organization of HP1-type proteins and LBR can explain some of the diverse protein-protein interactions at the chromatin-lamina-membrane interface of the nuclear envelope... - Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210R E Nickowitz
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
J Exp Med 178:2237-42. 1993.... - Structural organization of the human gene (LMNB1) encoding nuclear lamin B1F Lin
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Genomics 27:230-6. 1995.... - Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1Q Ye
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 271:14653-6. 1996..LBR can interact with chromodomain proteins that are highly conserved in eukaryotic species and may function in the attachment of heterochromatin to the inner nuclear membrane in cells... - The human lamin B receptor/sterol reductase multigene familyL Holmer
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, New York, New York, 10032, USA
Genomics 54:469-76. 1998..These results describe a human gene family encoding proteins of the inner nuclear membrane and endoplasmic reticulum that function in nuclear organization and/or sterol metabolism... - A human HP1 pseudogene maps to chromosome 11p14A Park
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Somat Cell Mol Genet 24:353-6. 1998..These results demonstrate that HP1-type sequences have been duplicated multiple times in the mammalian genome... - Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiersK K Hwang
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 98:11423-7. 2001..These data provide genetic evidence that an HP1-family protein represses the expression of euchromatic genes in a metazoan, and that histone modifiers cooperate with HP1 in euchromatic gene repression... - Inner nuclear membrane proteins: functions and targetingL Holmer
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
Cell Mol Life Sci 58:1741-7. 2001..Associations with nuclear ligands retain them in the inner nuclear membrane. Further investigation of the functions and targeting of inner nuclear membrane proteins are needed to determine how they are involved in human disease... - Nuclear envelope proteins and neuromuscular diseasesCecilia Ostlund
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, Tenth Floor, New York, New York 10032, USA
Muscle Nerve 27:393-406. 2003..This review gives an overview of this topic and describes recent advances in identification of disease-causing mutations, studies of cells and tissues from subjects with these diseases, and animal and cell culture models... - Emery-Dreifuss muscular dystrophyAntoine Muchir
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Curr Neurol Neurosci Rep 7:78-83. 2007.... - Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type laminsAntoine Muchir
Departments of Medicine and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Biochem Biophys Res Commun 351:1011-7. 2006.... - Pathology and nuclear abnormalities in hearts of transgenic mice expressing M371K lamin A encoded by an LMNA mutation causing Emery-Dreifuss muscular dystrophyYuexia Wang
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Hum Mol Genet 15:2479-89. 2006..These results demonstrate that expression of a lamin A mutant that induces alterations in nuclear morphology can cause tissue and organ damage in mice with a normal complement of wild-type lamins... - The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domainSandrine Caputo
Département d Ingénierie et d Etudes des Protéines Direction des Sciences du Vivant, Bâtiment 152, Commissariat à l Energie Atomique Saclay, 91191 Gif sur Yvette Cedex, France
J Biol Chem 281:18208-15. 2006..This suggests that MAN1 binds simultaneously to R-Smads and their targeted DNA sequences... - Intracellular trafficking and dynamics of double homeodomain proteinsCecilia Ostlund
Department of Medicine, College of Physicians and Surgeons, Columbia University, Room 10 509, 630 West 168th Street, New York, New York 10032, USA
Biochemistry 44:2378-84. 2005..DUX1 is more mobile than DUX4 within the nucleus (t(1/2) = 4.8 s for DUX1 and 13.4 s for DUX4), suggesting differences in the way the two proteins interact with nuclear components... - Dependence of diffusional mobility of integral inner nuclear membrane proteins on A-type laminsCecilia Ostlund
Department of Medicine, College of Physicians and Surgeons, Columbia University, Room 10 509, 630 West 168th Street, New York, New York 10032, USA
Biochemistry 45:1374-82. 2006..This supports a model where emerin and MAN1 are at least partly retained in the inner nuclear membrane by binding to A-type lamins, while LBR depends on other binding partners for its retention... - Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophyRevekka L Boguslavsky
Department of Medicine and Anatomy, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Hum Mol Genet 15:653-63. 2006..They also had increased basal phosphorylation of AKT1, a mediator of insulin signaling. We conclude that A-type lamins act as inhibitors of adipocyte differentiation, possibly by affecting PPARgamma2 and insulin signaling... - Epidermal expression of the truncated prelamin A causing Hutchinson-Gilford progeria syndrome: effects on keratinocytes, hair and skinYuexia Wang
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Hum Mol Genet 17:2357-69. 2008.... - Intracellular trafficking of MAN1, an integral protein of the nuclear envelope inner membraneWei Wu
Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Cell Sci 115:1361-71. 2002..These results are in agreement with the 'diffusion-retention' model for targeting integral proteins to the inner nuclear membrane... - Expression of lamin A mutated in the carboxyl-terminal tail generates an aberrant nuclear phenotype similar to that observed in cells from patients with Dunnigan-type partial lipodystrophy and Emery-Dreifuss muscular dystrophyCatherine Favreau
, Institut Jacques Monod, CNRS, , 75251, Paris Cedex 05, France
Exp Cell Res 282:14-23. 2003..Transfected cells therefore develop similar phenotypes when expressing lamins mutated in the carboxyl-terminal tail at sites responsible for FPLD or EDMD... - Gene regulation by human orthologs of Drosophila heterochromatin protein 1Kyu Kye Hwang
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10th Floor, Room 508, New York, NY 10032, USA
Biochem Biophys Res Commun 293:1217-22. 2002..These results show that different human HP1 family proteins can potentially repress or activate the same genes... - MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signalingFeng Lin
Department of Medicine and Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Hum Mol Genet 14:437-45. 2005..These results show that the nuclear envelope regulates a signal transduction pathway and have implications for how mutations in nuclear envelope proteins cause different human diseases... - Lamin-associated proteinsCecilia Ostlund
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Methods Cell Biol 78:829-59. 2004 - The carboxyl-terminal region common to lamins A and C contains a DNA binding domainVerene Stierle
Département de Biologie Supramoléculaire et Cellulaire, Institut Jacques Monod CNRS UMR 7592, Universités Paris 6 Paris 7, 2 place Jussieu, 75251 Paris Cedex 05, France
Biochemistry 42:4819-28. 2003..We conclude that the carboxyl-terminal end of lamins A and C binds DNA and suggest that alterations in lamin-DNA interactions may play a role in the pathophysiology of some lamin-linked diseases... - Effect of pathogenic mis-sense mutations in lamin A on its interaction with emerin in vivoIan Holt
Biochemistry Group, North East Wales Institute, Wrexham LL11 2AW, UK
J Cell Sci 116:3027-35. 2003..Subtle effects on the function of the lamina-emerin complex in EDMD/CMD1A patients might be responsible for the skeletal and/or cardiac muscle phenotype... - Nuclear envelope, nuclear lamina, and inherited diseaseHoward J Worman
Department of Medicine and Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Int Rev Cytol 246:231-79. 2005..In this review, we summarize fundamental aspects of nuclear envelope structure and function, the inherited diseases caused by mutations in lamins and other nuclear envelope proteins, and possible pathogenic mechanisms... - Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophyAntoine Muchir
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA
Hum Mol Genet 16:1884-95. 2007..Activation of MAPK signaling appears to be a cornerstone in the development of heart disease in both X-linked and autosomal dominant EDMD... - Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosisShinji Shimoda
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
Gastroenterology 124:1915-25. 2003..Virtually all patients with PBC have antimitochondrial autoantibodies (AMA), but, interestingly, approximately 50% also manifest antinuclear antibodies (ANA)... - Antinuclear antibodies specific for primary biliary cirrhosisHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10th Floor, Room 508, New York, NY 10032, USA
Autoimmun Rev 2:211-7. 2003..While antibodies against gp210, sp100 and some other nuclear proteins are very specific to PBC and may therefore be useful diagnostic markers, their connection to pathogenesis remains to be elucidated... - Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophyAntoine Muchir
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street New York, NY 10032, USA
J Clin Invest 117:1282-93. 2007..Activation of MAPK signaling by mutant A-type lamins could be a cornerstone in the development of heart disease in autosomal dominant Emery-Dreifuss muscular dystrophy... - NMR assignment of region 655-775 of human MAN1Sandrine Caputo
, CEA Saclay, 91191, Gif-sur-Yvette, France
J Biomol NMR 36:2. 2006 - The nuclear envelope and human diseaseAntoine Muchir
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Physiology (Bethesda) 19:309-14. 2004..We review what is known about nuclear lamin function and the different diseases caused by mutations in lamins A and C and associated inner nuclear membrane proteins... - Hepatic steatosis in Dunnigan-type familial partial lipodystrophyAngelika Lüdtke
Department of Gastroenterology, Hepatology and Endocrinology, Charite, Campus Mitte, Humboldt University, Berlin, Germany
Am J Gastroenterol 100:2218-24. 2005..The goal of this study was to determine the prevalence of steatosis in subjects with FPLD... - 1H, 13C and 15N resonance assignments of the C-terminal domain of human lamin A/CIsabelle Krimm
J Biomol NMR 22:371-2. 2002 - Components of the nuclear envelope and their role in human diseaseHoward J Worman
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10th Floor, Room 508, New York, NY 10032, USA
Novartis Found Symp 264:35-42; discussion 42-50, 227-30. 2005..Further studies of nuclear envelope proteins may uncover additional unsuspected relationships to human disease... - The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophyIsabelle Krimm
Departement d Ingenierie et d Etudes des Proteines, CEA Saclay, 91191, Gif sur Yvette, France
Structure 10:811-23. 2002..Our structure determination and mutant analyses clearly show that the consequences of the mutations causing muscle-specific diseases or lipodystrophy are different at the molecular level... - A-type lamins: guardians of the soma?Chris J Hutchison
School of Biological and Biomedical Sciences, The University of Durham, South Road, Durham, DH1 4EB, UK
Nat Cell Biol 6:1062-7. 2004..Thus, the degenerative nature of laminopathies is explained because these lamins are essential for maintenance of somatic tissues in adulthood...
Research Grants
- Pathogenesis of Emery-Dreifuss Muscular DystrophyHoward J Worman; Fiscal Year: 2010....
- Nucleocytoplasmic Interactions and Dynamics in Emery-Dreifuss Muscular DystrophyHoward Worman; Fiscal Year: 2009....
- Pathogenesis of Emery-Dreifuss Muscular DystrophyHoward J Worman; Fiscal Year: 2010....
- Nucleocytoplasmic Interactions and Dynamics in Emery-Dreifuss Muscular DystrophyHoward J Worman; Fiscal Year: 2010....
- Pathogenesis of Emery-Dreifuss Muscular DystrophyHoward Worman; Fiscal Year: 2009....
- Nucleocytoplasmic Interactions and Dynamics in Emery-Dreifuss Muscular DystrophyHoward Worman; Fiscal Year: 2009....
- Pathogenesis of Emery-Dreifuss Muscular DystrophyHoward Worman; Fiscal Year: 2007..This work will help establish how abnormalities in the nuclear envelope cause muscular dystrophy. ..
- Lamin A Mutation and Hutchinson-Gilford ProgeriaHoward Worman; Fiscal Year: 2007..This project will establish how mutations in nuclear lamins A and C cause HGPS, and if inhibition of protein farnesylation is a potential therapeutic intervention. ..
- DUX4 and Facioscapulohumeral Muscular DystrophyHoward Worman; Fiscal Year: 2004..This work could lead to the development of new diagnostic methods as well as the identification of potential protein targets for the treatment of FSHD. ..
- Lamin A in Adipocyte Differentation and SurvivalHoward Worman; Fiscal Year: 2004..Confirmation of this hypothesis will have implications for the identification of new cellular targets to treat human obesity and diabetes mellitus. ..
- Pathogenesis of Emery-Dreifuss Muscular DystrophyHoward J Worman; Fiscal Year: 2010..The results obtained in this project will identify targets for therapeutic interventions in EDMD and related disorders caused by LMNA and EMD mutations. ..