Esophageal cancer is the third leading cancer in males and fourth leading in females in India, but not much is known about the molecular etiology of the disease. We have used DNA microarray technology for high throughput identification of molecular gene expression profiles. We observed 881 genes significantly upregulated in ESCC samples as compared to the adjacent normal epithelium. The expression of two previously unreported overexpressed genes, ORAOV2 and FAP, was validated at the protein level by immunohistochemical labeling of tissue microarrays and archival tissue sections. Overall, using this approach, we have identified a number of promising novel candidates that can be validated further for their potential to serve as biomarkers for ESCC. This is a collaborative effort between IOB, Kidwai Memorial Institute of Oncology and Johns Hopkins School of Medicine. Similarly, we are working on copy number variations in ESCC using arrayCGH.

Similar approaches are adopted for diverse cancers such as pancreatic cancer, gastric adenocarcinoma, gall bladder carcinoma, hepatocellular carcinoma, leukoplakia and oral squamous cell carcinoma, cervical cancer and retinoblastoma. Other diseases for which transcriptomic profiling are being done include temporal lobe epilepsy, tuberculous meningitis, rheumatoid arthritis, osteoarthritis, spondyloarthropathy and reactive arthritis.  We also use this technology to identify subset of genes which are responsible for the development of skin lesions in arsenic exposed patients.

X-linked mental retardation is a common child hood disorder.  Identification of precise molecular mechanisms involved in these diseases should lead to better classification, diagnosis, prevention and therapy.  It is anticipated that several genes and mechanisms that may play a role in X-linked mental retardation. Using a custom designed microarray for comparative genomic hybridization, we are carrying out this investigation planning to identify genetic mechanisms and potential molecules that play a major role in the etiology of mental retardation. The discovery of genes involved in mental retardation will be helpful in the diagnosis, classification and therapy of the disorder.

Kinases and phosphatases have an equal role to play in phosphorylation and dephosphorylation of proteins that are responsible for transmitting signals from an external stimulus to the final expression of required functional genes through a cascade of signaling molecules.  However, actions of phosphatases are less investigated as opposed to kinases. We are identifying substrates of protein tyrosine phosphatases that are involved in human diseases in a global scale using substrate trapping mutants of protein tyrosine phosphatases in order to evaluate their functional aspects that will result in the identification of lead molecules for therapeutic interventions.