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Tapas
Mukhopadhyay Ph.D.
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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