Tapas Mukhopadhyay Ph.D.

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Dr. Mukhopadhyay was born in Calcutta, India. He received his M.S. degree from Calcutta University, Calcutta, India, and his Ph.D. from Banaras Hindu University, India. After completing his Ph.D., he joined the Tata Cancer Research Institute, Bombay India, as a Scientific Officer. In 1985 Dr. Mukhopadhyay joined M.D. Anderson Cancer Center as a Postdoctoral Fellow in the Department of Molecular Pathology. He joined the Department of Thoracic and Cardiovascular Surgery as a Research Associate and became an Assistant Professor. He is a member of several national and international professional associations including the American Association of Cancer Research. Dr. Mukhopadhyay has published a number of papers in peer-reviewed journals and several book chapters. He is first author of a book entitled p53 Suppressor Gene.

Information

Tapas Mukhopadhyay, Ph.D.
Assistant Professor and Assistant Biologist

Offices:

Department of Thoracic and Cardiovascular Surgery
The University of Texas M. D. Anderson Cancer Center
1515 Holcombe Boulevard, Box 109
Houston, TX 77030-4095
Phone: (713) 745-4502
Fax: (713) 794-4901
E-mail:tmukhopa

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Education:

• Calcutta University, Calcutta, India, B.S., 1975
• Calcutta University, Calcutta, India, MS, 1977
• Banaras Hindu University, Varanasi, India, Ph.D., 1981

Society Memberships:

• American Association of Cancer Research
• Indian Association for Cancer Research
• Indian Society for Cell Biology

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Research Interests:

p53 protein, gene expression, apoptosis, gene therapy

p53 is the central component of a complex network of signaling pathways responsible for the maintenance of genomic integrity. My primary interest is to elucidate the mechanism by which p53 protein modulates growth and apoptosis in cancer cells. My hypothesis is that a high level of wild-type p53 accumulation is necessary to induce apoptotic cancer cell death, while a low or moderate level of wild-type p53 induction can result in growth arrest of the cancer cells. To test this hypothesis, I am analyzing cell growth and apoptotic activity in human lung cancer cell lines after modulation of p53 protein in the cell using a number of different biochemical and molecular techniques.

Many groups have tried to circumvent the loss of tumor suppressor function in cancer cells by taking advantage of the fact that about 50% of tumors retain the mutated p53 gene and that introducing exogenous wild-type p53 cDNA into tumor cells can inhibit their growth. These efforts have had mixed success because the half-life of the wild-type p53 protein is very short, and it is often very difficult to elevate the level of intracellular p53 protein by simple exogenous delivery of the p53 cDNA into the cell. Overexpression of exogenous wild-type p53 alone can suppress the growth of p53-mutated or p53-deleted lung cancer cell lines but is generally insufficient to induce their apoptosis. In contrast, introduction of wild-type p53 via an adenoviral vector (Ad5p53) is known to induce apoptosis in some tumor cell lines in which p53 is deleted or mutated. In general, however, about half of all tumors or tumor cell lines that contain wild-type p53 are refractory to p53-mediated growth arrest or apoptosis. Moreover, the efficacy of Ad5p53 delivery in tumors is limited unless the vector is used at a high multiplicity of infection (MOI). We have circumvented this problem by transducing cells with wild-type p53-containing adenoviral vectors at an MOI as low as 1 and then treating them with 2-methoxyestradiol, resulting in apoptosis irrespective of the tumors' p53 status. This induction of apoptosis is associated with increased intracellular levels of p53, suggesting that it results from inhibition of p53 degradation. Thus, stabilization of wild-type p53 protein in the cells could be an important determinant of a cell's decision to undergo apoptosis. A number of biochemical and biological agents can modulate wild-type p53 function; therefore, identification and characterization of such agents are important for p53-mediated gene therapy.

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• Curriculum Vitae