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Shobha Vasudevan, Ph.D.

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Available: 01/10/22, Expires: 03/01/24

Quiescent (G0) cancer cells are dormant, reversibly-arrested cells, including stem cells, which resist clinical therapy that eliminates proliferating cancer cells. Upon chemotherapy removal, G0 cells sense the loss of their proliferating neighbors and restart cell division, restoring the cancer as recurrence. G0 shows a switch to a distinct gene expression program where RNA regulation enables persistence of this critical state. mRNA control elements and noncoding RNAs that regulate mRNAs, interact with RNA binding proteins to direct expression of clinically important genes. RNAs are also chemically modified to alter their functions in G0 tumor cells, which enables tumor survival. Deregulation of these processes leads to tumor resistance, immune and developmental disorders. The primary goal of our research program is to investigate RNA mechanisms that express critical genes in tumors, which lead to clinical and immune resistance, permitting tumor expansion. We will analyze noncoding RNAs, translation mechanisms, ribosome changes, chemical modification enzymes, and associated effectors, in resistant tumors and stem cells to uncover how tumors persist. These findings will be used to develop new therapeutic approaches to alter RNA-controlled expression and curb tumor resistance. These investigations will provide insights on RNA mechanisms and novel therapeutics to curtail tumor persistence. Prior Skills: Molecular and cell biology skills are great but not necessary; a deep interest in understanding, in tackling cancer, and persistence is needed.

Available: 12/04/22, Expires: 12/30/24

We investigate RNA mechanisms of gene expression regulation in quiescent, clinically resistant cancer cells. Tumors demonstrate heterogeneity, harboring a small subpopulation that switch from proliferation to a reversibly arrested state of quiescence that decreases their susceptibility to chemotherapy. Our data revealed that post-transcriptional mechanisms are altered by stress signaling in such quiescent, drug resistant cells in leukemias. Conventional post-transcriptional mechanisms are reduced, with modification of RNAs, associated complexes & ribosomes that enable specialized gene expression. The primary goal of our research is to characterize the specialized gene expression program in quiescent drug resistant cells in cancers, & the RNA mechanisms that contribute to tumor persistence, using in vitro & in vivo systems. We will comprehensively characterize the altered post-transcriptional & translational gene expression in drug resistant cancers. This will yield insights into the differences that underlie clinical resistance & tumor survival & can lead to new therapeutic options. We will elucidate the regulation of RNAs & ribosomes, by G0- & therapy-induced DNA damage & stress signaling that we have observed to alter post-transcriptional mechanisms in drug resistant cells. This will shed light on drug survival adaptations that operate via RNA mechanism changes in cancers. We will utilize our findings to develop therapeutic applications that interfere with RNA mechanisms that drive key regulators in resistant cancer. These will impair unique RNA mechanisms in persisted cancer cells without affecting normal cells, to curb expression of survival regulators & curtail tumor persistence. Projects available for students with either molecular biology, cell culture, cancer biology, informatics, or related experience, interested in translating basic studies into therapeutic avenues & committed to research.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R35GM134944 (VASUDEVAN, SHOBHA) Jun 9, 2020 - Mar 31, 2025
    NIH
    Specialized post-transcriptional mechanisms of gene expression in quiescence
    Role: Principal Investigator
  2. R21CA220103 (VASUDEVAN, SHOBHA) Jan 15, 2020 - Dec 31, 2021
    NIH
    Role of RNA methylation in chemoresistant cancer cells
    Role: Principal Investigator
  3. R01GM100202 (VASUDEVAN, SHOBHA) Feb 13, 2015 - Jun 30, 2020
    NIH
    Post-transcriptional Gene Expression of the TNF alpha by an FXR1a-associated microRNP
    Role: Principal Investigator
  4. R01CA185086 (VASUDEVAN, SHOBHA) Jun 1, 2014 - May 31, 2019
    NIH
    (PQC6) Molecular Determinants of Quiescent Cancer Cells
    Role: Principal Investigator

Bibliographic
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.