Vidya Gopalakrishnan, Ph.D.
Department of Pediatrics, Division of Pediatrics Division
About Dr. Gopalakrishnan
Medulloblastoma is a highly malignant pediatric brain tumor that is postulated to arise from the undifferentiated stem/progenitor cells of the external granule layer of the developing cerebellum. A number of studies have linked medulloblastoma genesis to aberrations in normal cerebellar development.
The overall goal of our research is to understand the role of the RE1 Silencing Transcription Factor (REST), a negative regulator of neuronal differentiation, in cerebellar development and in medulloblastoma pathogenesis. Our earlier work demonstrated that aberrant maintenance of REST expression in human medulloblastoma cell lines and immortalized cerebellar progenitors maintained proliferation, blocked neuronal specification and promoted tumor formation in the murine cerebellum. Countering REST activity in these cells induced neurogenesis and abrogated their tumorigenic potential in vivo, suggesting an important role for REST in tumor genesis.
Ongoing research in our laboratory is focused on understanding the mechanism(s) by which REST is regulated during normal neurogenesis of cerebellar stem/progenitor cells and if aberrations in these regulatory mechanisms contribute to medulloblastoma genesis. We are also interested in identifying downstream effectors of REST that may contribute to neoplasia in cerebellar stem/progenitor cells. In the long-term, these studies are expected to identify novel targets for medulloblastoma therapy.
Additional links:
Center for Cancer Epigenetics: http://www.mdanderson.org/education-and-research/departments-programs-and-labs/programs-centers-institutes/center-for-cancer-epigenetics/index.html
UT Graduate School website: http://gsbs.uth.tmc.edu/tutorial/gopalakrishnan_v.html
PubMed publication list: http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/12GE65p075iG7oOGayl15pbAU/
Education & Training
Degree-Granting Education
| 1995 | University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, PHD, Microbiology |
| 1988 | University of Bombay, Bombay, IND, MS, Biochemistry |
| 1986 | University of Bombay, Bombay, IND, BS, Microbiology and Biochemistry |
Postgraduate Training
| 1995-2001 | Post-Doctoral Fellowship, Molecular Genetics/Biochemistry, The Johns Hopkins University School of Medicine, Baltimore, MD |
Honors & Awards
| 1997 | Fellow, Leukemia and Lymphoma Society of America |
| 1997 | Fellow, Ruth L. Kirschstein National Research Service Award (NRSA)/NIH (Relinquished due to overlap with Leukemia and Lymphoma Society grant) |
| 1989 | Fellow, Ben Franklin Biotechnology Training Program, Pittsburgh, PA |
| 1988 | Scholar, J. N. Tata Endowment, India |
| 1988 | Fellow, Dean's List-University of Pittsburgh, School of Medicine |
| 1983 | Scholar, State of Maharashtra Government, India |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Das CM, Taylor P, Gireud M, Singh A, Lee D, Fuller G, Ji L, Fangusaro J, Rajaram V, Goldman S, Eberhart C, Gopalakrishnan V.. The deubiquitylase USP37 links REST to the control of p27 stability and cell proliferation. Oncogene 32(13):1691-701, 2013. PMID: 33665064.
- Taylor P, Fangusaro J, Rajaram V, Goldman S, Helenowski IB, MacDonald T, Hasselblatt M, Riedemann L, Laureano A, Cooper L, Gopalakrishnan V. REST Is a novel prognostic factor and therapeutic target for medulloblastoma. Mol Cancer Ther 11(8):1713-23, 2012. PMID: 22848092.
- Singh A, Rokes C, Gireud M, Fletcher S, Baumgartner J, Fuller G, Stewart J, Zage P, Gopalakrishnan V.. Retinoic acid induces REST degradation and neuronal differentiation by modulating the expression of SCF(β-TRCP) in neuroblastoma cells. Cancer 117(22):5189-202, 2011. PMID: 21523764.
- Schreck KC, Taylor HP, Marchionni L, Gopalakrishnan V, Bar EE, Gaiano N, and Eberhart CG. The Notch target HES1 directly modulates Gli1 expression and Hedgehog signaling: A potential mechanism of therapeutic resistance. Clin Cancer Res 16(24):6060-70, 2010. PMID: 21169257.
- Kong M, Zhang M, Gopalakrishnan V, Wolff J. Dose-Time-Effect modeling for cancer cell growth in In-vitro experiments. Stat Biopharm Res 2(1):84-96, 2010.
- Prasad P, Vasquez H, Das CM, Gopalakrishnan V, Wolff JE. Histone acetylation resulting in resistance to methotrexate in choroid plexus cells. J Neurooncol 91(3):279-86, 2009. PMID: 18853233.
- Aguilera DG, Das CM, Sinnappah-Kang ND, Joyce C, Taylor PH, Wen S, Hasselblatt M, Paulus W, Fuller G, Wolff JE, Gopalakrishnan V. Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL. J Neurooncol 93(3):303-18, 2009. PMID: 19148581.
- Masoudi A, Elopre M, Amini E, Nagel ME, Ater JL, Gopalakrishnan V, Wolff JE. Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res 28(4C):2437-42, 2008. PMID: 18751431.
- Zhang M, Aguilera D, Das C, Vasquez H, Zage P, Gopalakrishnan V, Wolff J. Measuring cytotoxicity: A new perspective on LC50. Anticancer Res 27(1A):35-8, 2007. PMID: 17352213.
- Das CM, Aguilera D, Vasquez H, Prasad P, Zhang M, Wolff JE, Gopalakrishnan V. Valproic acid induces p21 and topoisomerase-II (alpha/beta) expression and synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines. J Neurooncol 85(2):159-70, 2007. PMID: 17534580.
- Zhang M, Das C, Vasquez H, Aguilera D, Zage PE, Gopalakrishnan V, Wolff JE. Predicting tumor cell repopulation after response: mathematical modeling of cancer cell growth. Anticancer Research 26:2933-6, 2006. PMID: 16886616.
- Su X*, Gopalakrishnan V*, Stearns D, Aldape K, Lang FF, Fuller G, Snyder E, Eberhart CG, Majumder S (*Equal Contribution). Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Molecular Cell Biology 26:1666-78, 2006. PMID: 16478988.
- Watanabe Y, Kameoka S, Gopalakrishnan V, Aldape KD, Pan ZZ, Lang FF, Majumder S (Equal Contribution). Conversion of myoblasts to physiologically active neuronal phenotype. Genes & Development 18:889-900, 2004. PMID: 15078815.
- Gopalakrishnan V, Simancek P, Houchens C, Snaith HA, Frattini MG, Sazer S, Kelly TJ. Redundant control of rereplication in fission yeast. Proceedings of the National Academy of Sciences U S A 98:13114-9, 2001. PMID: 11606752.
- Gopalakrishnan V, Sheahan L, Khan SA. DNA replication specificity and functional E2 interaction of the E1 proteins of human papillomavirus types 1a and 18 are determined by their carboxyl-terminal halves. Virology 256:330-9, 1999. PMID: 10191198.
- Khan SA, Sheikh S, Sheahan L, Van Horn G, Gopalakrishnan V, Sverdrup F. Expression of E1 protein of human papillomaviruses in eukaryotic cells. Methods Enzymol 306:328-36, 1999. PMID: 10432463.
- Gopalakrishnan V, Walker S, Khan SA. Stimulation of human papillomavirus type 1a DNA replication by a multimerized AT-rich palindromic sequence. Virology 214(1):301-6, 1995. PMID: 8525634.
- Gopalakrishnan V, Khan SA. E1 protein of human papillomavirus type 1a is sufficient for initiation of viral DNA replication. Proc Natl Acad Sci U S A 91(20):9597-601, 1994. PMID: 7937813.
Invited Articles
- Gopalakrishnan V. REST and the RESTless: in stem cells and beyond. Future Neurol 4(3):317-329, 2009. PMID: 19885378.
Abstracts
- Rokes C, Zage PE, Gopalakrishnan V. Retinoic Acid Promotes Proteasomal Degradation of REST and Neuronal Differentiation in Neuroblastoma Cells. Abstract at the 23rd Annual Meeting of The American Society of Pediatric Hematology/Oncology, Montreal, Quebec, Canada, 2010.
- Aguilera DG, Rajaram V, Fangusaro J, Tomita T, Gopalakrishnan V, Wen S, Goldman S. REST Expression and its Prognostic Relevance in Ependymomas. Abstract from the 2009 Joint Meeting of SNO and AANS/CNS Section on Tumors, New Orleans, LA, 2009.
- Das C, Taylor P, Gopalakrishnan V. NRSF-mediated Regulation of p27/CDKNIB: Implications for Medulloblastoma Cell Proliferation. Abstracts of the American Association for Cancer Research Genetics and Biology of Brain Tumors Meeting, San Diego, CA, 2009.
- Das C, Aguilera D, Kommagari R, Thomas A, Joyce C, Wolff J, Kadakia M, Gopalakrishnan V. Synergy Between HDAC Inhibitors and Etoposide in Medulloblastoma Cells: p53-dependent and Independent Mechanisms. Abstracts of the American Association for Cancer Research 99th Annual Meeting, San Diego, CA, 2008.
- Aguilera D, Das CM, Wolff JEA, Zage PE, and Gopalakrishnan V. Valproic Acid Enhances Etoposide-Induced Cytotoxicity in Neuroblastoma Cells. Presented at the Advances in Neuroblastoma Research (ANR) Conference, Chiba, Japan, 2008.
- Masoudi A, Elopre M, Amini E, Nagel M, Ater J, Gopalakrishnan V, Wolff J. Valporic acid in the treatment of pediatric high grade glioma: Retrospective chart review. Abstracts of the Society of Neuro-oncology, Dallas, TX, 2007.
- Gopalakrishnan V, Anderson P, Das C, Aguilera D, Vasuez H, Prasad P, Zhang M, Wolff J.. Valproic Acid Sensitizes High Grade Glioma Cells to Etoposide. Abstract of the SIOP Meetings, Mumbai, India, 2007.
- Das C, Aguilera DG, Vasquez H, Zhang M, Prasad P, Wolff JE, Gopalakrishnan V. Valproic acid enhances cytotoxicity of etoposide in human glioblastoma cells. Abstracts of the AACR Meeting, Los Angeles, CA, 2007.
- Aguilera V, Wolff J and Gopalakrishnan V. Histone de-acetylase inhibitors in medulloblastoma therapy. Abstracts of the International Society of Pediatric Oncology, Geneva, Switzerland, 2006.
- Gopalakrishnan V. A novel therapeutic target for medulloblastomas. Abstracts of the Society of Neuro-Oncology Annual Meeting, Orlando, FL, 2006.
- Aguilera V Vasquez H, Das C, Wolff J and Gopalakrishnan V. Epigenetic changes in medulloblastoma. Abstracts of the International Brain Tumor Meeting, Tokyo, Japan, 2006.
- Aguilera V, Vasquez H, Das C, Wolff J and Gopalakrishnan V. Demethylating agents and histone de-acetylase inhibitors in medulloblastoma. Abstracts of the American Society for Clinical Oncology, San Francisco, CA, 2006.
- Gopalakrishnan V, Fuller G, Su X, Price R, Cohen Z, Lang F, Sawaya R, Majumder S. Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron restrictive silencing factor, which can be functionally countered by REST-VP16. Abstracts of the University of California, San Francisco Pediatric Brain Tumor Meeting, Napa Valley, CA, 2006.
- Aguilera D, Zage P, Wolff J and Gopalakrishnan V. Effect of the HDAC inhibitor MS-275 on medulloblastoma growth and viability. Abstracts of the Society of Neuro-Oncology Annual Meeting, Orlando, FL, 2006.
- Das C, Zage P, Wolff J and Gopalakrishnan V. Study of valproic acid as a chemosensitizer in medulloblastoma therapy. Abstracts of the Society of Neuro-Oncology Annual Meeting, Orlando, FL, 2006.
- Aguilera V, Vasquez H, Das C, Gopalakrishnan V, Wolff J. Demethylating agents and histone de-acetylase inhibitors in medulloblastoma. Abstracts of the 12th International Symposium on Pediatric Neuro-Oncology, Washington, DC, 2005.
- Majumder S, Gopalakrishnan V, Su X, Kameoka S. REST/NRSF, a key player in medulloblastoma tumorigenesis. Abstracts of the Brain Tumor Society, Houston, TX, 2004.
- Gopalakrishnan V, Simancek P, Houchens C, Snaith H A, Sazer S, Kelly TJ. Interaction of Cdt1 and Cdc18 in the control of S. pombe DNA replication. Abstracts of the DNA Replication Meeting, Cold Spring Harbor, NY, 2001.
- Gopalakrishnan V, Simancek P, Houchens C, Kelly TJ. The role of fission yeast protein Cdt1 in the initiation of DNA replication. Abstracts of the Cell Cycle Meeting, Cold Spring Harbor, NY, 2000.
Book Chapters
- Gopalakrishnan V, Aguilera D. Epigenetic Control of Apoptosis in Brain Tumors: Implications for Therapy. In: Cell Death and Cancer. Research SignPost, 2009.