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. Protein synthesis is a complex process that ensures organismal homeostasis by controlling the quantity and quality of the proteome. The pervasiveness of translational control is evident in the genesis and progression of diseases such as cancer and ribosomopathies such as Shwachman-Bodian-Syndrome that are a consequence of deregulated protein synthesis. We are primarily interested in understanding the molecular mechanisms that regulate the 60S ribosomal factors and their contributions to translational control in response to nutrient stress, genotoxic stress and other stressors in specific cell types.
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60S Ribosomal Maturation and Translation Initiation
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. eIF6 is a key regulator of 60S biogenesis and activity. Our recent work has identified novel post-translational modifications of eIF6 that is dependent on the state of stress. We are currently exploring the mechanism of regulation of 60S ribosomal maturation and availability by eIF6 and maturation factors and its role in cancers and ribosompathies. |
eIF6 function in 60S synthesis, maturation and in inhibiting 40S interaction.
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Murine stem cell enriched spheroids
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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. |
Translational mechanisms that control cancer progression
Since the 1800s, enlarged nucleoli are considered a hallmark of cancer cells. Enlarged nucleoli serve as hubs of enhanced ribosome biogenesis, thereby leading to increased production of proteins that sustain the uncontrolled growth and proliferation of cancer cells. Our research is focused on understanding the contributions of translational control towards tumor initiation and progression towards malignancy. We are currently investigating the interplay of translational factors, ribosomal maturation factors and tumor suppressors such as p53 that are critical for DNA damage response. These efforts will help to identify novel targets that will eventually provide parallel or alternate means for cancer therapeutics.
Since the 1800s, enlarged nucleoli are considered a hallmark of cancer cells. Enlarged nucleoli serve as hubs of enhanced ribosome biogenesis, thereby leading to increased production of proteins that sustain the uncontrolled growth and proliferation of cancer cells. Our research is focused on understanding the contributions of translational control towards tumor initiation and progression towards malignancy. We are currently investigating the interplay of translational factors, ribosomal maturation factors and tumor suppressors such as p53 that are critical for DNA damage response. These efforts will help to identify novel targets that will eventually provide parallel or alternate means for cancer therapeutics.
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.
