National Institute of Biomedical Genomics, Noida, India
I have been working in the area of human disease for more than fifteen years. Currently my research focus is to understand the host response to tuberculosis in a genome wide approach. My current project focuses on characterisation of host markers that plays role in determining susceptibility to tuberculosis and development of drug resistance if any. Besides, we also want to characterise and correlate other host immune parameters. Previously our work on identification of determinant of host factors in granuloma formation, have successfully demonstrated that cytokines TNFα and IFNγ play positive role in granuloma formation but not in bacterial clearance. Host metabolic responses (as determined by activation of VitD receptor and inhibition of GPR109A) to Mtb infection may be more relevant in influencing mycobacterial growth. To understand the genomic modulators of active and no disease after prolonged exposure we profiled cytokines of active TB patients and their households. We found that chemokine CXCL10 expression is significantly high AFB positive patients compare to AFB negative individuals both at protein and RNA level. CXCL10 is activated in active phase of infection and can be a biomarker for active phase of the disease. Genetic factors modulating such responses are also investigated in a genome wide manner using exome chip. We have published our findings in Tuberculosis journal and other manuscripts are under preparation (see publication list). Also I have participated in the project to identify metabolites in different biofliuds like serum, urine, sputum from active TB patients (publications mentioned) to identify a metabolite signature.
My previous experience includes work on various genetic diseases that includes congenital heart disease and sterol metabolic disorders. I am competent in disease gene identification, mutation screening, DNA sequencing, genotyping. I am also well acquainted with functional study of diseased genes using cell culture and knock out/knock in animals.
Role of host genomics in determining susceptibility to tuberculosis, Molecular mechanisms underlying Congenital heart disease