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Vidya Gopalakrishnan, Ph.D.

Present Title & Affiliation

Dual/Joint/Adjunct Appointment

Associate Professor, Department of Pediatrics - Research, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX
Associate Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Bio Statement

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, PHD, Microbiology
1988 University of Bombay, Bombay, India, MS, Biochemistry
1986 University of Bombay, Bombay, India, BS, Microbiology and Biochemistry

Postgraduate Training

8/1995-5/2001 Post-Doctoral Fellowship, Cell Cycle Regulation of DNA Replication in Fission Yeast, Molecular Genetics/Biochemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, Dr. Thomas J. Kelly

Experience/Service

Other Appointments/Responsibilities

Member, The University of Texas Graduate School of Biomedical Sciences Program in Neuroscience, Houston,, TX, 2008-present
Graduate Faculty, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, 2006-present

Institutional Committee Activities

Member, The University of Texas Graduate School of Biomedical Sciences Program in Neuroscience Admissions Committee, 2008-present
Member, Center for Stem Cell and Developmental Biology, 2008-present
Member, Institutional Research Grant Committee - Basic Research, 10/2007-5/2010
Member, Center for Cancer Epigenetics, 2007-present
Member, Brain Tumor Center, 2003-present

Honors and Awards

1997-2000 Fellow, Leukemia and Lymphoma Society of America
1997-2000 Fellow, Ruth L. Kirschstein National Research Service Award (NRSA)/NIH (Relinquished due to overlap with Leukemia and Lymphoma Society grant), 1997-2000
1989-1990 Fellow, Ben Franklin Biotechnology Training Program, Pittsburgh
1988-1989 Fellow, Dean's List, School of Medicine, University of Pittsburgh
1988 Scholar, J. N. Tata Endowment, India
1983-1988 Scholar, State of Maharashtra Government, India

Professional Memberships

American Association for Cancer Research (AACR), Philadelphia, PA
Member, 2006-present
Society for Neuro-Oncology, Bellaire, TX
Member, 2006-present
Society of Neuro-Oncology International Outreach Committee, Houston, TX
Member, 2006-present

Selected Publications

Peer-Reviewed Original Research Articles

1. 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. PMCID: PMC44860.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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, Jan-Feb, 2007. PMID: 17352213.
10. 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.
11. 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, Jul-Aug, 2008. PMID: 18751431.
12. 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, 2/2009. e-Pub 10/2008. PMID: 18853233.
13. 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, 7/2009. e-Pub 1/2009. PMID: 19148581.
14. 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, 2/2010.
15. 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, 11/2011. PMID: 21523764.
16. 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, 12/2010. PMCID: PMC3059501.
17. 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, 8/2012. PMID: 22848092.
18. 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. Onogene, 6/2012. e-Pub 6/2012. PMCID: PMC3435483.

Invited Articles

1. Gopalakrishnan V. REST and the RESTless: in stem cells and beyond. Future Neurol 4(3):317-329, 2009. PMCID: PMC2719900.

Abstracts

1. 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.
2. 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 (#A16), 2009.
3. 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.
4. 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 (#3746), 2008.
5. 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.
6. 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.
7. 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.
8. 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.
9. Gopalakrishnan V. A novel therapeutic target for medulloblastomas. Abstracts of the Society of Neuro-Oncology Annual Meeting, Orlando, FL, 2006.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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

1. Gopalakrishnan V and Aguilera D. Epigenetic Control of Apoptosis in Brain Tumors: Implications for Therapy. In: Cell Death and Cancer. Ed(s) A Basu. Research SignPost. In Press.

Last updated: 2/5/2013