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Shobha Vasudevan, Ph.D.


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: 01/04/21, Expires: 12/30/22

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 persister 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.

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
    Specialized post-transcriptional mechanisms of gene expression in quiescence
    Role: Principal Investigator
  2. R21CA220103 (VASUDEVAN, SHOBHA) Jan 15, 2020 - Dec 31, 2021
    Role of RNA methylation in chemoresistant cancer cells
    Role: Principal Investigator
  3. R01GM100202 (VASUDEVAN, SHOBHA) Feb 13, 2015 - Jun 30, 2020
    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
    (PQC6) Molecular Determinants of Quiescent Cancer Cells
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Nomburg J, Zou W, Frost TC, Datta C, Vasudevan S, Starrett GJ, Imperiale MJ, Meyerson M, DeCaprio JA. Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses. PLoS Pathog. 2022 Apr 01; 18(4):e1010401. PMID: 35363834.
    Citations:    Fields:    
  2. Guo H, Golczer G, Wittner BS, Langenbucher A, Zachariah M, Dubash TD, Hong X, Comaills V, Burr R, Ebright RY, Horwitz E, Vuille JA, Hajizadeh S, Wiley DF, Reeves BA, Zhang JM, Niederhoffer KL, Lu C, Wesley B, Ho U, Nieman LT, Toner M, Vasudevan S, Zou L, Mostoslavsky R, Maheswaran S, Lawrence MS, Haber DA. NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer. Mol Cell. 2021 10 07; 81(19):4041-4058.e15. PMID: 34624217.
    Citations:    Fields:    Translation:HumansAnimalsCells
  3. Chen H, Yang H, Zhu X, Yadav T, Ouyang J, Truesdell SS, Tan J, Wang Y, Duan M, Wei L, Zou L, Levine AS, Vasudevan S, Lan L. m5C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat Commun. 2020 06 05; 11(1):2834. PMID: 32503981.
    Citations: 24     Fields:    Translation:HumansAnimalsCells
  4. Lee S, Micalizzi D, Truesdell SS, Bukhari SIA, Boukhali M, Lombardi-Story J, Kato Y, Choo MK, Dey-Guha I, Ji F, Nicholson BT, Myers DT, Lee D, Mazzola MA, Raheja R, Langenbucher A, Haradhvala NJ, Lawrence MS, Gandhi R, Tiedje C, Diaz-Muñoz MD, Sweetser DA, Sadreyev R, Sykes D, Haas W, Haber DA, Maheswaran S, Vasudevan S. A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells. Genome Biol. 2020 02 10; 21(1):33. PMID: 32039742.
    Citations: 9     Fields:    Translation:HumansAnimalsCells
  5. Ebright RY, Lee S, Wittner BS, Niederhoffer KL, Nicholson BT, Bardia A, Truesdell S, Wiley DF, Wesley B, Li S, Mai A, Aceto N, Vincent-Jordan N, Szabolcs A, Chirn B, Kreuzer J, Comaills V, Kalinich M, Haas W, Ting DT, Toner M, Vasudevan S, Haber DA, Maheswaran S, Micalizzi DS. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. Science. 2020 03 27; 367(6485):1468-1473. PMID: 32029688.
    Citations: 56     Fields:    Translation:HumansAnimalsCells
  6. Li B, Clohisey SM, Chia BS, Wang B, Cui A, Eisenhaure T, Schweitzer LD, Hoover P, Parkinson NJ, Nachshon A, Smith N, Regan T, Farr D, Gutmann MU, Bukhari SI, Law A, Sangesland M, Gat-Viks I, Digard P, Vasudevan S, Lingwood D, Dockrell DH, Doench JG, Baillie JK, Hacohen N. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. Nat Commun. 2020 01 09; 11(1):164. PMID: 31919360.
    Citations: 37     Fields:    Translation:HumansCells
  7. Chery J, Petri A, Wagschal A, Lim SY, Cunningham J, Vasudevan S, Kauppinen S, Näär AM. Development of Locked Nucleic Acid Antisense Oligonucleotides Targeting Ebola Viral Proteins and Host Factor Niemann-Pick C1. Nucleic Acid Ther. 2018 10; 28(5):273-284. PMID: 30133337.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  8. Bukhari SIA, Truesdell SS, Vasudevan S. Analysis of MicroRNA-Mediated Translation Activation of In Vitro Transcribed Reporters in Quiescent Cells. Methods Mol Biol. 2018; 1686:251-264. PMID: 29030826.
    Citations: 1     Fields:    Translation:HumansCells
  9. Martinez I, Hayes KE, Barr JA, Harold AD, Xie M, Bukhari SIA, Vasudevan S, Steitz JA, DiMaio D. An Exportin-1-dependent microRNA biogenesis pathway during human cell quiescence. Proc Natl Acad Sci U S A. 2017 06 20; 114(25):E4961-E4970. PMID: 28584122.
    Citations: 21     Fields:    Translation:HumansCells
  10. Bukhari SI, Vasudevan S. FXR1a-associated microRNP: A driver of specialized non-canonical translation in quiescent conditions. RNA Biol. 2017 02; 14(2):137-145. PMID: 27911187.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  11. Le Tonqueze O, Kollu S, Lee S, Al-Salah M, Truesdell SS, Vasudevan S. Regulation of monocyte induced cell migration by the RNA binding protein, FXR1. Cell Cycle. 2016 07 17; 15(14):1874-82. PMID: 27229378.
    Citations: 9     Fields:    Translation:HumansCells
  12. Bukhari SIA, Truesdell SS, Lee S, Kollu S, Classon A, Boukhali M, Jain E, Mortensen RD, Yanagiya A, Sadreyev RI, Haas W, Vasudevan S. A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence. Mol Cell. 2016 Mar 03; 61(5):760-773. PMID: 26942679.
    Citations: 36     Fields:    Translation:HumansAnimalsCells
  13. Solé X, Alves CP, Dey-Guha I, Ritsma L, Boukhali M, Lee JH, Chowdhury J, Ross KN, Haas W, Vasudevan S, Ramaswamy S. AKT Inhibition Promotes Nonautonomous Cancer Cell Survival. Mol Cancer Ther. 2016 Jan; 15(1):142-53. PMID: 26637368.
    Citations: 14     Fields:    Translation:HumansAnimalsCells
  14. Lee S, Truesdell SS, Bukhari SI, Lee JH, LeTonqueze O, Vasudevan S. Upregulation of eIF5B controls cell-cycle arrest and specific developmental stages. Proc Natl Acad Sci U S A. 2014 Oct 14; 111(41):E4315-22. PMID: 25261552.
    Citations: 18     Fields:    Translation:HumansAnimalsCells
  15. Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, Lu J, Shioda T, Vasudevan S, Ramaswamy S, Maheswaran S, Diederichs S, Haber DA. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes Dev. 2013 Dec 01; 27(23):2543-8. PMID: 24298054.
    Citations: 72     Fields:    Translation:HumansCells
  16. Lee S, Vasudevan S. Post-transcriptional stimulation of gene expression by microRNAs. Adv Exp Med Biol. 2013; 768:97-126. PMID: 23224967.
    Citations: 39     Fields:    Translation:HumansAnimalsCells
  17. Truesdell SS, Mortensen RD, Seo M, Schroeder JC, Lee JH, LeTonqueze O, Vasudevan S. MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP. Sci Rep. 2012; 2:842. PMID: 23150790.
    Citations: 65     Fields:    Translation:HumansAnimalsCells
  18. Vasudevan S. Functional validation of microRNA-target RNA interactions. Methods. 2012 Oct; 58(2):126-34. PMID: 22910526.
    Citations: 10     Fields:    Translation:HumansCells
  19. Chen AJ, Paik JH, Zhang H, Shukla SA, Mortensen R, Hu J, Ying H, Hu B, Hurt J, Farny N, Dong C, Xiao Y, Wang YA, Silver PA, Chin L, Vasudevan S, Depinho RA. STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA. Genes Dev. 2012 Jul 01; 26(13):1459-72. PMID: 22751500.
    Citations: 62     Fields:    Translation:HumansAnimalsCells
  20. Letonqueze O, Lee J, Vasudevan S. MicroRNA-mediated posttranscriptional mechanisms of gene expression in proliferating and quiescent cancer cells. RNA Biol. 2012 Jun; 9(6):871-80. PMID: 22699554.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  21. Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012 May-Jun; 3(3):311-30. PMID: 22072587.
    Citations: 168     Fields:    Translation:HumansAnimalsCells
  22. Mortensen RD, Serra M, Steitz JA, Vasudevan S. Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc Natl Acad Sci U S A. 2011 May 17; 108(20):8281-6. PMID: 21536868.
    Citations: 58     Fields:    Translation:HumansAnimalsCells
  23. Steitz JA, Vasudevan S. miRNPs: versatile regulators of gene expression in vertebrate cells. Biochem Soc Trans. 2009 Oct; 37(Pt 5):931-5. PMID: 19754429.
    Citations: 31     Fields:    Translation:HumansAnimalsCells
  24. Vasudevan S, Tong Y, Steitz JA. Cell-cycle control of microRNA-mediated translation regulation. Cell Cycle. 2008 Jun 01; 7(11):1545-9. PMID: 18469529.
    Citations: 68     Fields:    Translation:HumansAnimalsCells
  25. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007 Dec 21; 318(5858):1931-4. PMID: 18048652.
    Citations: 1175     Fields:    Translation:HumansCells
  26. Vasudevan S, Steitz JA. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell. 2007 Mar 23; 128(6):1105-18. PMID: 17382880.
    Citations: 291     Fields:    Translation:HumansCells
  27. Vasudevan S, Seli E, Steitz JA. Metazoan oocyte and early embryo development program: a progression through translation regulatory cascades. Genes Dev. 2006 Jan 15; 20(2):138-46. PMID: 16418480.
    Citations: 32     Fields:    Translation:HumansAnimalsCells
  28. Vasudevan S, Garneau N, Tu Khounh D, Peltz SW. p38 mitogen-activated protein kinase/Hog1p regulates translation of the AU-rich-element-bearing MFA2 transcript. Mol Cell Biol. 2005 Nov; 25(22):9753-63. PMID: 16260593.
    Citations: 10     Fields:    Translation:AnimalsCells
  29. Duttagupta R, Vasudevan S, Wilusz CJ, Peltz SW. A yeast homologue of Hsp70, Ssa1p, regulates turnover of the MFA2 transcript through its AU-rich 3' untranslated region. Mol Cell Biol. 2003 Apr; 23(8):2623-32. PMID: 12665566.
    Citations: 15     Fields:    Translation:AnimalsCells
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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.