Research Interests
Our research aims to uncover the signaling mechanisms that regulate critical cellular processes based on the polarizing physiological cues of growth and stress. We are primarily interested in understanding the molecular mechanisms that regulate the 60S ribosomal factors and their contributions to translational control and the interplay of DNA repair mechanisms under normal and diseased states including cancer and ribosomopathies. We use an array of cellular, molecular, biochemical and in vivo approaches to address these fundamental mechanistic questions.
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60S Dynamics, Translation Initiation and Cancer
Eukaryotic protein synthesis is predominantly regulated at the initiation stage by controlling the function of eukaryotic initiation factors (eIFs) and by regulating the fitness and availability of ribosomes. Our recent work has uncovered a novel signaling mechanism that regulates ribosomal availability and translational rates in response to nutrient stress. We are currently investigating the structure-function relationships of translational initiation factors (eIF6), 60S ribosomal maturation factors, Ribosome Quality Control (RQC), and the 60S ribosomal structural dynamics that are critical for stress response. These efforts will help to identify novel targets that will provide parallel or alternate means for cancer therapeutics and for treatment of ribosomopathies such as Shwachman-Diamond-Syndrome. |
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DNA Repair: Modulators of Homologous Recombination
Our lab is also focussed on understanding the regulation of HR mediators. HR-mediated repair of DNA strand breaks is crucial for the maintenance of genomic stability. However, it is imperative that HR is tightly regulated to ensure that spurious HR or insufficient HR response does not lead to additional genomic changes and chromosomal rearrangements. Our lab has uncovered novel regulation of modulators of the initial stages of HR such as RPA and is currently assessing their effects on cellular checkpoint responses to genomic damage.
Our lab is also focussed on understanding the regulation of HR mediators. HR-mediated repair of DNA strand breaks is crucial for the maintenance of genomic stability. However, it is imperative that HR is tightly regulated to ensure that spurious HR or insufficient HR response does not lead to additional genomic changes and chromosomal rearrangements. Our lab has uncovered novel regulation of modulators of the initial stages of HR such as RPA and is currently assessing their effects on cellular checkpoint responses to genomic damage.
Protein Synthesis and Stem cells
Adult stem cells are essential for maintaining tissue integrity by serving as a renewed source of cells. Interestingly, most adult stem cells exhibit lower rates of protein synthesis compared to their progenitor cells. It is unclear as to how such low rates of protein synthesis are maintained in stem cells and how they influence the stem cell response to stress. Protein synthesis regulation in adult stem cells in vastly under explored. We are interested in understanding the mechanisms that regulate the translation initiation machinery and influence protein synthesis rates in adult stem cell biology that will aid in therapeutic application of stem cells. (Image shows colonic 3D stem cell enriched spheroids).
Adult stem cells are essential for maintaining tissue integrity by serving as a renewed source of cells. Interestingly, most adult stem cells exhibit lower rates of protein synthesis compared to their progenitor cells. It is unclear as to how such low rates of protein synthesis are maintained in stem cells and how they influence the stem cell response to stress. Protein synthesis regulation in adult stem cells in vastly under explored. We are interested in understanding the mechanisms that regulate the translation initiation machinery and influence protein synthesis rates in adult stem cell biology that will aid in therapeutic application of stem cells. (Image shows colonic 3D stem cell enriched spheroids).
