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Shobha Vasudevan, PH.D.

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Available: 04/18/17, Expires: 04/28/20

Research Assistant/Student positions available at Massachusetts General Hospital Cancer Center (Simches Building, Boston) in a lab working on non-coding RNAs and microRNAs and their roles/mechanisms in cancers and development using cancer cell lines, stem cells and Xenopus oocytes.

My research program aims to investigate the mechanisms of gene expression control of critical genes by non-coding RNAs, microRNAs and RNA-protein complexes (RNPs), their regulation and interconnections in response to quiescent and hypoxic conditions in tumors, stem cells and germ cells. Quiescent (G0) cells include an assortment of reversibly-arrested cells, including dormant stem cells. G0 cancer cells resist clinical therapy and prevent irreversible arrest, while maintaining the ability to re-enter the cell cycle, thus eventually leading to cancer chemoresistance and recurrence. G0 demonstrates a switch to a distinct gene expression program where post-transcriptional changes, including mRNA untranslated region (UTR) elements such as AU-rich elements (AREs), altered RNPs, non-coding RNAs and microRNAs contribute to the maintenance of this state. AREs are highly conserved mRNA 3'-UTR regulatory elements while microRNAs are small non-coding RNAs that target distinct UTR sites and control post-transcriptional gene expression of clinically relevant messages; their deregulation leads to a broad range of critical effects such as tumor progression, immune and developmental disorders.

The primary goal of our research program is to investigate non-coding RNA, microRNA- and RNA binding protein-controlled expression of critical genes; in particular, of clinically relevant mRNAs that lead to tumor progression and maintain quiescent cells in cancers and thereby, resistance and recurrence. An interconnected direction of our research is to investigate ARE and microRNP regulation in cancers and development, specifically, in response to quiescent conditions in tumor cell lines, stem cells and in Xenopus laevis germ cells (oocytes). There are four core directions:

1. To functionally characterize microRNAs and specific non-coding regulatory RNAs, their associated cofactors and target mRNAs that control essential cell state regulators using previously developed in vivo crosslinking coupled affinity purification methods and confirmatory assays

2. To investigate the mechanism of gene expression in distinct cellular conditions and the interconnections between AREs and microRNPs

3. To elucidate the regulation of expression and function of microRNAs and AREs by specific cellular conditions

4. To develop antisense manipulations of selective interactions between regulatory RNAs and their mRNA targets as specific therapeutic approaches to interfere with gene expression essential for the cancer G0 cell state and thereby, abrogate resistant G0 cells in cancer.

These studies should provide a greater understanding of the versatile roles of regulatory non-coding RNAs in cancers and development and lead to novel approaches in small RNA-based therapeutic applications.


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. R01GM100202 (VASUDEVAN, SHOBHA) Feb 13, 2015 - Jan 31, 2020
    NIH/NIGMS
    Post-transcriptional Gene Expression of the TNF alpha by an FXR1a-associated microRNP
    Role: Principal Investigator
  2. R01CA185086 (VASUDEVAN, SHOBHA) Jun 1, 2014 - May 31, 2018
    NIH/NCI
    (PQC6) Molecular Determinants of Quiescent Cancer Cells
    Role: Principal Investigator

Bibliographic
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. 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:    Fields:    
  2. 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
  3. 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: 6     Fields:    Translation:HumansCells
  4. 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:    Fields:    Translation:HumansAnimalsCells
  5. 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: 3     Fields:    Translation:HumansCells
  6. 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: 9     Fields:    Translation:HumansAnimalsCells
  7. 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: 5     Fields:    Translation:HumansAnimalsCells
  8. 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: 10     Fields:    Translation:HumansAnimalsCells
  9. 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: 32     Fields:    Translation:HumansCells
  10. Lee S, Vasudevan S. Post-transcriptional stimulation of gene expression by microRNAs. Adv Exp Med Biol. 2013; 768:97-126. PMID: 23224967.
    Citations: 28     Fields:    Translation:HumansAnimalsCells
  11. 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: 32     Fields:    Translation:HumansAnimalsCells
  12. Vasudevan S. Functional validation of microRNA-target RNA interactions. Methods. 2012 Oct; 58(2):126-34. PMID: 22910526.
    Citations: 7     Fields:    Translation:HumansCells
  13. 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: 41     Fields:    Translation:HumansAnimalsCells
  14. 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: 2     Fields:    Translation:HumansAnimalsCells
  15. Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012 May-Jun; 3(3):311-30. PMID: 22072587.
    Citations: 87     Fields:    Translation:HumansAnimalsCells
  16. 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: 45     Fields:    Translation:HumansAnimalsCells
  17. 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: 27     Fields:    Translation:HumansAnimalsCells
  18. 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: 57     Fields:    Translation:HumansAnimalsCells
  19. 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: 905     Fields:    Translation:HumansCells
  20. 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: 222     Fields:    Translation:HumansCells
  21. 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: 28     Fields:    Translation:HumansAnimalsCells
  22. 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
  23. 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: 14     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.