Hara P. Ghosh, PhD

Hara P. Ghosh, PhD

Professor Emeritus
Biochemistry and Biomedical Sciences
Associate Professor- Pathology and Molecular Biology

4H39A Health Sciences Centre
McMaster University
905-525-9140 x 22451
ghosh@mcmaster.ca

• Cancer Biology- Therapeutics and Biochemistry

Research

Membrane fusion, virus entry and virus assembly

The fusion of membranes is an event essential for biological processes such as oocyte fertilization, vesicular transport, synaptic transmission and entry of enveloped viruses. The glycoprotein of an enveloped animal virus induces fusion between the viral envelope and cell membrane leading to virus infection. Our focus is to study: (i) how proteins induce fusion between viral and cell membranes for virus entry, (ii) how the infectious viruses are assembled, and (iii) the structure-function relationship of fusogenic membrane glycoproteins. The assembly and fusion events are potentially important targets for drug therapies directed against enveloped viruses such as, influenza, HIV, Ebola, etc.

Role of a novel tumor suppressor gene in lung cancer

Tumor suppressor genes are "guardian genes" for control of cell proliferation. Failure of tumor suppressor genes to function properly causes uncontrolled cell growth leading to cancer. A novel tumor suppressor gene (TSLC1) has been identified in human lung cancer. The TSLC1 gene encodes a transmembrane glycoprotein which contain sequences homologous to NCAM cell adhesion proteins as well as sequences that bind proteins containing FERM- and PDZ-domains. Expression of TSLC is abrogated or reduced in non-small cell lung cancer, hepatocellular carcincoma and pancreatic cancer cells. Our objective is to understand the normal functions of TSLC and the consequences of its inactivation in cancer cells.

Selected Publications

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Kuramochi, M., Fukuhara, H., Nobukuni, T., Kanbe, T., Maruyama, T., Ghosh, H.P., Pletcher, M., Isomura, M., Onizuka, M., Kitamura, T., Sekiya, T., Reeves, R.H. and Murakami, Y. (2001) Nature Genetics 27: 427-430.

Helper virus-free HSV-1 vectors packaged both in the presence of VSV G protein and in the absence of HSV-1 glycoprotein B supports gene transfer into neurons in the rat striatum. Tang, J., Yang, T., Ghosh, H.P. and Geller, A.I. (2001) J. Neurovirology.

Pseudotyping of glycoprotein D-deficient herpes simplex virus type 1 with vesicular stomatitis virus glycoprotein G enables mutant virus attachment and entry. Anderson, D.B., Laquerrie, S., Ghosh, K., Ghosh, H.P., Goins, W.F., Cohen, J.B. and Glorioso, J.C. (2000) J. Virol. 74: 2481-2487, 7698.

Role of the membrane anchoring and cytoplasmic domains in intracellular transport and localization of viral glycoproteins. Ghosh, K. and Ghosh, H.P. (1999) Biochem. & Cell Biol. 77: 165-178.

Effects of double-site mutations of vesicular stomatitis virus glycoprotein G on membrane fusion activity. Shokralla, S., Chernish, R. and Ghosh, H.P. (1999) Virology 256: 119-129.

Requirement for a non-specific glycoprotein cytoplasmic domain sequence to drive efficient budding of vesicular stomatitis virus. Schnell, M.J., Bunacore, L., Boritz, E., Chernish, R., Ghosh, H.P. and Rose, J.K. (1998) EMBO J. 17: 1289-1296.