Vidya Gopalakrishnan, Ph.D.
Department of Pediatrics, Division of Pediatrics
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
- Shaik S, Maegawa S, Haltom AR, Wang F, Xiao X, Dobson T, Sharma A, Yang Y, Swaminathan J, Kundra V, Li XN, Schadler K, Harmanci A, Xu L, Gopalakrishnan V. REST promotes ETS1-dependent vascular growth in medulloblastoma. Mol Oncol 15(5):1486-1506, 2021. e-Pub 2021. PMID: 33469989.
- Bailey CP, Figueroa M, Gangadharan A, Yang Y, Romero MM, Kennis BA, Yadavilli S, Henry V, Collier T, Monje M, Lee DA, Wang L, Nazarian J, Gopalakrishnan V, Zaky W, Becher OJ, Chandra J. Pharmacologic inhibition of lysine-specific demethylase 1 as a therapeutic and immune-sensitization strategy in pediatric high-grade glioma. Neuro Oncol 22(9):1302-1314, 2020. PMID: 32166329.
- Khatua S, Cooper LJN, Sandberg DI, Ketonen L, Johnson JM, Rytting ME, Liu DD, Meador H, Trikha P, Nakkula RJ, Behbehani GK, Ragoonanan D, Gupta S, Kotrotsou A, Idris T, Shpall EJ, Rezvani K, Colen R, Zaky W, Lee DA, Gopalakrishnan V. Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma. Neuro Oncol 22(8):1214-1225, 2020. PMID: 32152626.
- Harmanci A, Harmanci AS, Swaminathan J, Gopalakrishnan V. EpiSAFARI: sensitive detection of valleys in epigenetic signals for enhancing annotations of functional elements. Bioinformatics 36(4):1014-1021, 2020. PMID: 31501853.
- Kennis BA, Michel KA, Brugmann WB, Laureano A, Tao RH, Somanchi SS, Einstein SA, Bravo-Alegria JB, Maegawa S, Wahba A, Kiany S, Gordon N, Silla L, Schellingerhout D, Khatua S, Zaky W, Sandberg D, Cooper L, Lee DA, Bankson JA, Gopalakrishnan V. Correction to: Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI. J Neurooncol 142(3):409, 2019. PMID: 30968268.
- Currier AW, Kolb EA, Gorlick RG, Roth ME, Gopalakrishnan V, Sampson VB. p27/Kip1 functions as a tumor suppressor and oncoprotein in osteosarcoma. Sci Rep 9(1):6161, 2019. e-Pub 2019. PMID: 30992462.
- Dobson THW, Tao RH, Swaminathan J, Maegawa S, Shaik S, Bravo-Alegria J, Sharma A, Kennis B, Yang Y, Callegari K, Haltom AR, Taylor P, Kogiso M, Qi L, Khatua S, Goldman S, Lulla RR, Fangusaro J, MacDonald TJ, Li XN, Hawkins C, Rajaram V, Gopalakrishnan V. Transcriptional repressor REST drives lineage stage-specific chromatin compaction at Ptch1 and increases AKT activation in a mouse model of medulloblastoma. Sci Signal 12(565), 2019. e-Pub 2019. PMID: 30670636.
- Dobson THW, Gopalakrishnan V. Preclinical Models of Pediatric Brain Tumors-Forging Ahead. Bioengineering (Basel) 5(4), 2018. e-Pub 2018. PMID: 30279402.
- Callegari K, Maegawa S, Bravo-Alegria J, Gopalakrishnan V. Pharmacological inhibition of LSD1 activity blocks REST-dependent medulloblastoma cell migration. Cell Commun Signal 16(1):60, 2018. e-Pub 2018. PMID: 30227871.
- Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, Chen K, Lee MG. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Mol Cell 70(5):825-841.e6, 2018. e-Pub 2018. PMID: 29861161.
- Nolo R, Herbrich S, Rao A, Zweidler-McKay P, Kannan S, Gopalakrishnan V. Targeting P-selectin blocks neuroblastoma growth. Oncotarget 8(49):86657-86670, 2017. e-Pub 2017. PMID: 29156825.
- Dobson THW, Hatcher RJ, Swaminathan J, Das CM, Shaik S, Tao RH, Milite C, Castellano S, Taylor PH, Sbardella G, Gopalakrishnan V. Regulation of USP37 Expression by REST-Associated G9a-Dependent Histone Methylation. Mol Cancer Res 15(8):1073-1084, 2017. PMID: 28483947.
- Somanchi SS, Kennis BA, Gopalakrishnan V, Lee DA, Bankson JA. In vivo (19)F-magnetic resonance imaging of adoptively transferred NK cells. Methods Mol Biol 1441:317-32, 2016. PMID: 27177678.
- Sandberg DI, Rytting M, Zaky W, Kerr M, Ketonen L, Kundu U, Moore BD, Yang G, Hou P, Sitton C, Cooper LJ, Gopalakrishnan V, Lee DA, Thall PF, Khatua S.. Methotrexate administration directly into the fourth ventricle in children with malignant fourth ventricular brain tumors: a pilot clinical trial. J Neurooncol 125(1):133-41, 2015. PMID: 26255071.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Tao RH, Brugmann W, Keith M, Somanchi S, Cooper L, Sandberg D, Khatua S, Zaky W, Moyes J, Schellingerhout D, Lee D, Bankson J and Gopalakrishnan V.. Novel Imaging agent to track infused cells for brain tumor immunotheraphy.
- Swaminathan J*, Singh A*, Taylor P, Fangusaro J, Rajaram V, Goldman S, Zweidler-McKay P, Hasselblatt M and Gopalakrishnan V.. Feedback control of REST transcription in medulloblastoma. (In preparation, *equal contribution).
- Bravo-Algeria JB, Maegawa S, Scutti JB, Brugmann W, Lee DA, Cooper LJN, Goldman S and Gopalakrishnan V.. MS-275 enhances sensitivity of DIPG cells to NK-mediated cytolysis by upregulating L1CAM expression. (In preparation).
- Taylor P*, Tao R*, Stratton S, Maegawa S, Singh A, Gireud M, Goldman S, Fangusaro J, Rajaram V, Hasselblatt M, Barton MC and Goplakrishnan V.. REST and HES1 co-occupy the p27 upstream regulatory region to coordinately regulate gene expression. (Nucleic Acids Research submitted, *equal contribution).
- Dhar S, Gu B, Lin T, Chen K, Pal K, McArthur MJ, Gopalakrishnan V, Shilatifard A, Li W, Sillitoe R and Lee MG.. MLL4 suppresses medulloblastoma by suppressing oncogenic pathways. (Molecular Cell-under revision).
- Tao RH*, Dobson T*, Shaik S, Taylor P, Kennis B, Qi L, Khatua S, Li X-N, Goldman S, Lulla R, Fangusaro J, MacDonald T, Li XN, Hawkins C, Rajaram V and Gopalakrishnan V.. A novel mouse model implicates histone H3 lysine 9 methylation in Ptch1 loss of heterozygosity and Akt hyperactivity in medulloblastoma. (Science Signaling-under revision *equal contribution).
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.
- 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.
- 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, 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 V, Wolff J and Gopalakrishnan V. Histone de-acetylase inhibitors in medulloblastoma therapy. Abstracts of the International Society of Pediatric Oncology, Geneva, Switzerland, 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.
- 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.
- 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 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.
- 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, 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.
Grant & Contract Support
| Title: | Developing NK cell immunotherapy for medulloblastoma and fourth ventricular tumors |
| Funding Source: | Stripes and Sunoco |
| Role: | Principal Investigator |
| Title: | Role of histone methyl transferase MLL4 in medulloblastoma |
| Funding Source: | NIH/NCI |
| Role: | Significant Contributor |
| Title: | Pediatric Solid Tumors Comprehensive Data Resource Core |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-Investigator |