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Howard Worman, M.D.

Associate Professor

E-mail: hjw14@columbia.edu


worman 
picture The nuclear envelope is composed of the nuclear membranes, the nuclear pore complexes and the nuclear lamina. The higher order structure of chromatin is influenced by its interactions with this organelle and nuclear envelope proteins and may play a role in the regulation of gene of chromatin is influenced by its interactions with this organelle and nuclear envelope proteins and may play a role in the regulation of gene expression. The nuclear envelope undergoes disassembly and reassembly during mitosis and cell cycle-dependent phosphorylation of protein components may regulate cell division. Research on the nuclear envelope is therefore of fundamental importance to our understanding of normal cell function as well as the pathobiology of cancer and other human diseases.

Over the years, we have characterized several nuclear envelope proteins and their genes. As many of the protein components of the nuclear membranes remain uncharacterized, part of our work remains focused on their identification and characterization. We are also examining how integral proteins are targeted to the inner nuclear membrane, the dynamics of these proteins during cell division and their interactions with other nuclear proteins and chromatin. In fairly recent work, we have shown that several human proteins, homologous to Drosophila heterochromatin protein HP1, interacts with LBR, an integral protein of the inner nuclear membrane. As HP1 is involved in the down regulation of gene expression in Drosophila, this finding suggests that the nuclear envelope may regulate gene HP1 is involved in the down regulation of gene expression in Drosophila, this finding suggests that the nuclear envelope may regulate gene expression by influencing chromatin organization.

The long-term, health-related interest of our group is the role of the nuclear envelope in human disease. Emerin, for example, is an integral protein of the inner nuclear membrane that is mutated and absent from the nuclear envelope in most individuals with X-linked Emery-Dreifuss muscular dystrophy. We are presently studying the functions of emerin and how its loss of function causes a specific disease. We are also continuing with our past work on nuclear envelope proteins that are recognized by autoantibodies from patients with primary biliary cirrhosis and primary sclerosing cholangitis and their significance in these poorly understood liver diseases.



Selected publications

Hwang, K-K, Eissenberg, JC, Worman HJ. 2001. Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers. Proc Natl Acad Sci USA. ;in press.

Laguri C, Gilquin B, Wolff N, Romi-Lebrun R, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S. 2001. Structural characterization of the LEM motif common to three human inner nuclear membrane proteins. Structure. 9:503-511.

Lin F, Blake DL, Callebaut I, Skerjanc IS, Holmer L, McBurney MW, Paulin-Levasseur M, Worman HJ. 2000. MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. J Biol Chem. 275:4840-4847.

Barton RM, Worman HJ. 1999. Prenylated prelamin A interacts with Narf, a novel nuclear protein. J Biol Chem. 274:30008-30018.

Ístlund C, Ellenberg J, Hallberg E, Lippincott-Schwartz J, Worman HJ. 1999. Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophy protein. J Cell Sci. 112:1709-1719.

Howard Worman's Medline citations



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Dept. of Anatomy & Cell Biology contact: Haesung Chung
Last modified on August 7, 2001