Vinay Tergaonkar obtained his Ph.D. (2001), from National Center for Biological Sciences, Bangalore, India, where he did his studies on the molecular pathogenesis of human papillomaviruses. During his graduate studies he was awarded an international cancer society (UICC) fellowship for collaborative research at Tufts University, Boston, USA. He has been a fellow (2001-2004) and a special fellow (2004-present) of the Leukemia and Lymphoma Society of America and conducted his postdoctoral studies at the Salk Institute for Biological Studies, La Jolla, California. He joins IMCB in 2005 as an Assistant Professor.

Adjunct appointments:
1) Department of Biochemistry (NUS)
2) Department of Pathology (NUH)

Editoral Boards:
1) Critical Reviews in Oncology/Hematology (Elsevier Press)
2) Biochemical Journal (Portland Press)

It is causally linked to the development of several human ailments including cancers. Deciphering the regulation of NFkB function is crucial to understanding the mechanism and role of constitutive NFkB activity seen in human malignancies. Dr Tergaonkar’s group has demonstrated that NFkB mitigates the function of the tumor suppressor protein p53, thereby promoting resistance to chemotherapy induced apoptosis. Thus blocking NFkB could be used as an adjuvant to existing chemotherapy regimens. Consistent with their data, NFkB inhibitors are showing promising results in clinical trials. Uncovering the mechanism of NFkB mediated resistance to physiologically relevant apoptotic stimuli is one of the group’s goals.

Given that over 200 physiological stimuli activate NFkB, which in turn regulates an equally large number of genes, understanding how specificity is generated in such a pleiotropic pathway is also a major challenge. Using a large-scale functional genomics approach, parallel interrogation of approximately 20,000 sequence-annotated genes was carried out and several novel modifiers of NFkB activity were identified. The group aims to characterize these proteins and the mechanisms by which they regulate NFkB.

A bottleneck in studying mammalian signaling lies in the ability to deliver genes/siRNAs to the desired cell types and also be able to turn these genes on or off at will. Recently, Dr. Tergaonkar has used lentiviruses, which can infect dividing and non-dividing cells of virtually any lineage, to generate transgenic mice with regulated expression or knock down of genes of interest. The lentiviral transgenesis approach can also be used for delineating functional domains/regulatory sites of a given protein in vivo and for generating human disease models. The group plans to analyze the candidates obtained in their genome wide screen using such approaches.

In resting cells, NFkB is bound to the IkB family of inhibitors. Degradation of IkB proteins in response to stimuli and subsequent covalent modifications of NFkB are essential for gene activation. Using mouse models, the group plans to investigate the modifications of NFkB that are critical for its role in development, inflammation and tumorigenesis. As a complementary approach, they will study cell lines and biopsies from human patients, to investigate the role of certain kinases, ubiquitin ligases and other modifying enzymes that might contribute towards deregulated NFkB activity in diseases.