ORIGANTI LAB
Saint Louis University
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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.  Deregulation of key translational and DNA repair mechanisms lead to the genesis and progression of diseases such as cancer, ribosomopathies such as Shwachman-Bodian-Syndrome, and inherited disorders. Uncovering these regulatory mechanisms presents an excellent opportunity to identify selective targets for therapeutic advancement.​​ 

​60S Ribosomal Maturation and Translation Initiation
Eukaryotic protein synthesis is predominantly regulated at the initiation stage by controlling the function of eukaryotic initiation factors and by regulating the fitness and availability of ribosomes. Based on the cellular context,  upstream signaling pathways regulate eIFs by altering their levels, or their activities via post-translational modifications such as methylation, phosphorylation or by reorganizing their spatial distribution. 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 effect of these post-translational modifications in altering eIF6 and 60S maturation and its role in Shwachman-Bodian-Syndrome.
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eIF6 function in 60S synthesis, maturation and in  inhibiting 40S interaction.
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 the protein synthesis rates in adult stem cells. Our efforts are aimed at understanding the fundamental biology of adult stem cells, which will help to expand the application of stem cells in regenerative medicine, and for treatment of cancer and other diseases.
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Murine stem cell enriched spheroids

Translational and DNA repair 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 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
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.

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