Environmental Toxicology

Environmental carcinogenesis, Oncogenes, Apoptosis, Growth factors & Immunotoxicology:

a) Environmental carcinogenesis:

Research interests are focus on three major areas:

i) identifying critical targets and mechanisms involved in the initiation and promotion stages of chemical carcinogenesis;

ii) exploring novel chemoprevention strategies for inhibiting chemical carcinogenesis; and

iii) collaborative molecular studies on the relationship between smoking, DNA adduct levels, and susceptibility to lung and other tobacco-related cancers in specific human populations.

b) Immunotoxicology:

Many mechanisms may contribute to immune depression observed following exposure to ionizing radiation, Heavy metal, radiation toxicity.

Addressing the following objectives may uncover and elucidate some of the mechanisms under lying immune depression following heavy metal (lead, nickel & cadmium etc.) radiation exposure.

= characterization of alterations in peripheral blood mononuclear cell and splenic mono nuclear cell subsets during heavy metal, radiation challenge

= to investigate the role of apoptosis in injury to mononuclear cells in

= the peripheral blood and spleen;

= to determine the role of in regulating different pro- and anti-apoptotic factors in of immune cell death following treatment

= to measure altered cytokine level in heavy metal or radiation induced environment.

c) Cell cycle, apoptosis, tumor suppressor genes:

The laboratory is focused on investigating the mechanisms involved in the development of cancer. One major focus is cell-cycle regulation in neoplastic development. We have studied the role of cyclin D1 and other cell-cycle regulators in ras transformation and in the development of chemically induced tumors. We also have developed a model of cell-cycle synchronization in the epidermis in vivo and we are investigating cell-cycle regulation by skin tumor promoters.

The laboratory has directed substantial efforts toward studying the mechanisms by which androgen regulates the cell-cycle machinery and the role of cell-cycle alterations in prostate cancer. We are studying changes in cell-cycle regulation in prostate cancer and cell-cycle alterations in the development of androgen-independent prostate tumors.

In addition, we have an active goal aimed at identifying the genetic targets for kidney and uterine cancer, including genes such as tumor suppressor genes (VHL and TSC-2) genes that regulate the cell cycle (cyclinD, p21, p27 and p16) and genes involved in tumor progression and metastasis (HIF-1 and VEGF).

d) p53 Regulation:

The role of the p53 tumor-suppressor gene product in cancer is of particular interest because p53 is the most commonly mutated gene in human cancers characterized to date. Cells that lack a functional p53 cannot undergo cell cycle arrest in response to DNA damage and will enter DNA synthesis with un repaired DNA. The molecular dynamics of the cellular response pathways that involve p53 in response to DNA damage are currently under intense scrutiny. DNA strand breaks, induced by either ionizing radiation or microinjection of a restriction endonuclease, have been shown to lead to an increase in p53. This increase requires the currently undefined gene product(s) that are defective in ataxia-telangiectasia, a cancer-prone inherited disease. The induction of p53 results in either cell cycle delay or initiation of programmed cell death (apoptosis), depending on the cell type. A practical application of a better understanding of this pathway might be the specific induction of apoptosis in tumor cells after exposure to therapeutic agents