The imbalance in the signaling network regulating cellular functions including proliferation, differentiation and cell survival results in cancer. Our group aims to identify and characterize the factors that are important for immortalization and transformation of cells which are critical for tumorigenesis.
Ras proteins are well-known small GTPases which are playing critical role in regulating cellular processes. In addition to the classical enzymatic effectors of Ras, non-enzymatic effectors grouped as “Ras-association domain containing family” (RASSF) proteins have been recently identified. The mechanism by which these proteins intercept tumor pathways is a key area of research in the lab.
Guanine nucleotide binding protein-like (GNL) - nuclear/nucleolar GTPases belong to the MMR1-HSR1 family of large putative GTPases which are emerging as crucial coordinators of signalling cascades in different cellular compartments. Members of this family are reported to regulate rRNA processing ribosome biogenesis as well as cell cycle. GNLs are reported to be overexpressed in several cancers and there are emerging evidence from our lab and others implicating their roles in cancer progression. Functional characterization of GNLs in relation with tumorigenesis is another area of research in the lab.
In a factory, someone has to stand on the loading dock, checking the goods going out. By recognizing labels like bar codes on each shipment, the loading dock supervisor makes sure that the products get where they are supposed to go. A cell is like a factory: one of its most important jobs is to produce proteins, like transcription factors and nuclear transport receptors. But in cellular factories, the sorting task is complicated by the fact that proteins are used by the cell itself as well as delivered to outside "customers". Scientists are succeeding at deciphering the cells complex bar-coding system. But, surprisingly, they have never managed to get at the loading dock itself to see how HIV PICs are actually shipped to their destinations.
Regulation of HIV-1 infectivity and pathogenesis of AIDS remain central interests of the laboratory. Unlike the typical animal-oncoretroviruses, lentiviruses such as HIV have the ability to infect and replicate within non-cycling cells. Nucleo-cytoplasmic transport of the viral genome is vital for the replication and assembly of many viruses. Nuclear transport of Human immunodeficiency viral (HIV) genome, for instance, is critical for productive infection in non-dividing cells such as human macrophages. Our understanding on the nuclear import of HIV preintegration complexes into the nucleus of non-dividing cells remains rudimentary, and identification of cellular protein(s) which interact with viral PICs is eagerly awaited and will reveal cellular system that are important to diverse and basic cellular processes. Our laboratory will focus on two issues: mechanism of HIV PICs nuclear import, and signals in PICs that regulate its nuclear import. To achieve this goal we will clone and characterize the host genes that are involved in this process. We will also attempt to identify how the host genes interact with viral proteins to bring about the events of HIV pathogenesis.
Furthermore, a better understanding of nuclear transport during viral infection might prove useful for designing antiviral therapies and for designing delivery vectors for gene therapy, which is a rapidly developing and increasingly important area of research in biomedical sciences.
Recent focus based on the interest in understanding Indian subtype C HIV-1, led us to work on development of a candidate HIV-1 envelope based vaccine. Our group is currently involved in testing the effect of vaccine in animal models such as mouse, rabbits and rhesus macaques.