Basic and translational radiobiological research:
- Radioresponse of cells: Cellular and molecular understanding of radio sensitivity of normal and tumour cells
- Rodiomoldulation: Radiation sensitisation of tumour cells and radioprotection of normal cells
- Anticancer drug screening: Synthetic, natural products and development of drug delivery systems (microspheres & liposomal) for improved antitumour effect
- Radiation biodosimetry: Development of assays for radiation biodosimetery and with conventional methodologies (dicentric chromosome assay, micronuclei assay, single cell gel electrophoresis assay (comet ), filter elution, and H2AX foci analysis. Influence of individual radiosensitivity in biodosimeteric estimations
- Development of predictive and prognostic assays for the assessment of clinical radio response
- Low dose radiation and bystander effect
- Molecular basis for normal tissue radio response with acute and chronic normal tissue toxicity after radiotherapy.
Toxicological research activities:
- Heavy metal toxicity (mercury, cobalt and lead) and its augmentation
- Pesticide and insecticide toxicology
- Genotoxicity and antigenotoxic potential of dietary constituents
- Toxicogenomics
Elucidation of the genetic basis for normal tissue radiosensitivity
Despite the rapid advances in the knowledge of cellular functions that affect radiosensitivity, we still cannot account for most of the clinically observed heterogeneity of normal tissue leading to more severe normal tissue damage after radiotherapy. Some of the recent findings have shed new light on the genetic basis that seems to underlie differences in normal tissue susceptibility / radiosensitivity and provide support for the concept of gene-based predictive tests for patients. The most convincing evidence in favor of this emanates from the studies highlighting the genetic basis for the radiosensitivity observed in the syndromes arising from gene defects such as Ataxia telangietasia (AT), Nijmegen breakage syndrome, and Fanconi anemia. Some of the differences in normal tissue sensitivity to radiation may stem from mutations with milder effects, heterozygosity, or polymorphisms of these genes. Candidate genes for which SNPs, deletion or loss of function mutations are known to be associated with altered cellular radiosensitivity are TGF ß1, GSTM1, GSTT1, GSTP1, NQO1, XRCC1, XRCC3 etc. It is becoming more convincing that the SNPs in genes involved in DNA damage detection and repair, pro-fibrotic and inflammatory cytokines; endogenous anti-oxidant enzymes have association with cellular radiosensitivity. Therefore, identification of novel SNPs, candidate genes and their polymorphism, comparison of already identified SNPs in varied human populations among the cancer patients are of prime importance for the molecular characterization of individuals who show therapeutic radiation sensitivity, eventually enabling the clinicians for tailoring of treatment to reduce the risk of developing life-threatening reactions.
Genetic basis of Radiosensitivity:
Radiotherapy is one of the major treatment armamentarium against cancer. Clinical experiences indicate that individual patient may show diverse degree of response to radiotherapy which might lead to secondary complications. Hence the goal of the therapy is to combat the tumor with acceptable side effects. In view of this, understanding the factors determining the individual responses to radiation becomes very important. Currently we are trying to understand the genetic basis for the normal tissue radiosensitivity for translating this knowledge for achieving improved therapeutic gain.
Modulation of radioresponse of cells:
One of the challenges faced in the treatment of solid tumors is radioresistance and associated normal tissue toxicities. Chemicals of biological origin have been proven to be good radio-modulating agents. In this regard, we have been exploring the bioactive chemical moieties from the natural and synthetic resources for their radiomodulating potentials.
Developing predictive tests for clinical radiation response assessment and for biodosimetry
Prediction of the treatment response prior to radiotherapy is off great significance as this information will be useful for appropriate treatment planning. Efforts are underway to develop novel assays for assessing the clinical radiation response. Similarly, efforts are underway to improve the sensitivity of the conventional biodosimeteric tools (dicentric chromosome assay, micronuclei assay, single cell gel electrophoresis assay, filter elution, and H2AX foci analysis) with the integrating of molecular knowledge.
Toxicological studies:
Heavy metal and pesticide toxicology
Exposure to heavy metal/pesticides has risen significantly over the past 50 years as a result of industrialization and the life style. Exposure to these agents poses serious and growing threat to the environment. Currently we are working on the effect of maternal exposure of methyl mercury and its consequences.
Nanotoxicology:
Nanotechnology, being an emerging field, is being extensively explored for the benefit of mankind. However, in order to achieve this, concurrent knowledge on the toxicological profile of nanoparticles to organisms is very essential. In our division, we are working on the toxicological effects of various metal nanoparticles on biological systems and its consequences at the genetic level with the aid of molecular and toxicogenomic approach.