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Deepa Sampath, Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

 

Epigenetic mechanisms play a critical role in the pathogenesis of leukemias and are rational targets for therapeutic modulation. Chronic lymphocytic leukemia and other indolent leukemias accumulate due to a persistence of cells with enhanced survival capacity. Resistance to apoptosis in these tumors is mediated by the selective repression of proapoptotic signaling pathways as well as the overexpression of survival promoting genes. Using CHIP assays, microarrays, gene expression assays and immunoblotting in primary tumor cells, research in my lab is focused on: 1) understanding the patterns of epigenetic silencing via methylation of DNA and histones, histone deacetylation and recruitment of polycomb repressor complexes to the gene promoters of microRNA and other genes in indolent leukemias, 2) Pharmacological re-expression with an aim to elucidating the physiological role of microRNA and other genes in regulating the apoptotic signaling in indolent leukemias. Our research projects provide the opportunity to study the epigenetic mechanisms that may contribute to the pathogenesis of indolent and aggressive leukemia and to translate these findings into novel therapeutic strategies against these diseases.

 

Education & Training

Degree-Granting Education

1995 University of Texas Medical Branch, Galveston, TX, PHD, Human Biological Chemistry and Genetics
1988 University of Madras, Chennai, Madras, India, MS, Medical Genetics
1986 University of Madras, Chennai, Madras, India, BS, Zoology

Postgraduate Training

3/1998-3/2004 Research Associate, The University of Texas MD Anderson Cancer Center, Houston, TX, Dr. William Plunkett
3/1995-3/1998 Postdoctoral Fellowship, The University of Texas MD Anderson Cancer Center, Houston, TX, Dr. William Plunkett

Experience/Service

Academic Appointments

Associate Faculty Member, Graduate School of Biomedical Sciences, Houston, TX, 2008-present
Instructor, Department of Experimental Therapeutics, Division of Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 3/2004-5/2007

Institutional Committee Activities

Member, Experimental Therapeutics Faculty Search Committee, 7/2008-present
Member, Departmental Growth Analysis Commitee, 6/2008
Member, Department of Experimental Therapeutics Research Seminar Committee, 1/2006-present

Selected Publications

Peer-Reviewed Original Research Articles
1. Sampath D, Jackson GR, Werrbach-Perez K, Perez-Polo JR. Effects of nerve growth factor on glutathione peroxidase and catalase in PC12 cells. J Neurochem 62:2476-2479, 1994. PMID: 8189251.
2. Jackson GR, Sampath D, Werrbach-Perez K, Perez-Polo JR. Effects of nerve growth factor on catalase and glutathione peroxidase in a hydrogen peroxide resistant pheochromocytoma subclone. Brain Research 634:69-76, 1994. PMID: 8156393.
3. Jackson GR, Werrbach-Perez K, Pan Z, Sampath D, Perez-Polo JR. Neurotrophin regulation of energy homeostasis in the central nervous system. Dev Neurosci 16:285-290, 1994. PMID: 7768207.
4. Sampath D, Holets V, Perez-Polo JR. Effect of a spinal cord photolesion injury on catalase. Int J Dev Neurosci 13:645-654, 1995. PMID: 8553900.
5. Sampath D, Perez-Polo JR. Regulation of antioxidant enzyme expression by NGF. Neurochem Research 22:351-362, 1997. PMID: 9130244.
6. Pan Z, Sampath D, Jackson G, Werrbach-Perez K, Perez-Polo R. NGF and oxidative stress in the nervous system. Adv in Exptl Med Biol 429:173-193, 1997.
7. Sampath D, Plunkett W. The role of c-jun kinase in the apoptotic response to nucleoside analogue-induced DNA damage. Cancer Research 60:6408-6415, 2000. PMID: 11103806.
8. Shi Z, Azuma A, Sampath D, Li YX, Huang P, Plunkett W. S-Phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine (UCN-01). Cancer Research 61:1065-1072, 2001. PMID: 11221834.
9. Sampath D, Shi Z, Plunkett W. Inhibition of cyclin-dependent kinase 2 by the Chk1-Cdc25A pathway during the S-phase checkpoint activated by fludarabine: dysregulation by 7-hydroxystaurosporine. Mol Pharmacol 62(3):680-688, 9/2002. PMID: 12181445.
10. Puduvalli VK, Sampath D, Bruner JM, Nangia J, Xu R, Kyritsis AP. TRAIL-induced apoptosis in gliomas is enhanced by Akt-inhibition and is independent of JNK activation. Apoptosis 10(1):233-243, 1/2005. PMID: 15711939.
11. Sampath D, Cortes J, Estrov Z, Du M, Shi Z, Andreeff M, Gandhi V, Plunkett W. Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood 107(6):2517-2524, 3/15/2006. e-Pub 11/17/2005. PMCID: PMC1895741.
12. Moufarij MA, Sampath D, Keating MJ, Plunkett W. Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal. Blood 108(13):4187-4193, 12/15/2006. e-Pub 9/5/2006. PMCID: PMC1895455.
13. Sampath D, Plunkett W. The role of DNA repair in chronic lymphocytic leukemia pathogenesis and chemotherapy resistance. Curr Oncol Rep 9(5):361-7, 9/2007. PMID: 17706164.
14. Ewald B, Sampath D, Plunkett W. H2AX phosphorylation marks gemcitabine-induced stalled replication forks and their collapse upon S-phase checkpoint abrogation. Mol Cancer Ther 4(4):1239-1248, 4/2007. e-Pub 4/3/2007. PMID: 17406032.
15. Ewald B, Sampath D, Plunkett W. ATM and the Mre11-Rad50-Nbs1 complex respondto nucleoside analogue-induces stalled replications forks and contribute to drug resistance. Cancer Res 68(19):7947-55, 10/1/2008. PMCID: PMC2631429.
16. Sampath D, Calin GA, Puduvalli VK, Gopisetty G, Taccioli C, Liu CG, Ewald B, Liu C, Keating MJ, Plunkett W. Specific activation of microRNA106b enables the p73 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation. Blood 113(16):3744-53, 4/16/2009. e-Pub 12/18/2008. PMCID: PMC2670791.
17. Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, Fabbri M, Lerner S, Barron LL, Rassenti LZ, Jiang L, Xiao L, Hu J, Secchiero P, Zauli G, Volinia S, Negrini M, Wierda W, Kipps TJ, Plunkett W, Coombes KR, Abruzzo LV, Keating MJ, Calin GA. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood 116(6):945-52, 8/12/2010. e-Pub 4/14/2010. PMID: 20393129.
18. Wierda WG, Castro JE, Aguillon R, Sampath D, Jalayer A, McMannis J, Prussak CE, Keating M, Kipps TJ. A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154. Leukemia 24(11):1893-900, 11/2010. e-Pub 9/2010. PMID: 20882050.
19. Fabbri M, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE, Valeri N, Calore F, Sampath D, Fanini F, Vannini I, Musuraca G, Dell'Aquila M, Alder H, Davuluri RV, Rassenti LZ, Negrini M, Nakamura T, Amadori D, Kay NE, Rai KR, Keating MJ, Kipps TJ, Calin GA, Croce CM. Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA 305(1):59-67, 1/5/2011. PMID: 21205967.
20. Xu J, Sampath D, Lang FF, Prabhu S, Rao G, Fuller GN, Liu Y, Puduvalli VK. Vorinostat modulates cell cycle regulatory proteins in glioma cells and human glioma slice cultures. J Neurooncol 105(2):241-51, 11/2011. e-Pub 5/20/2011. PMID: 21598070.
21. Zecevic A, Sampath D, Ewald B, Chen R, Wierda W, Plunkett W. Killing of chronic lymphocytic leukemia by the combination of fludarabine and oxaliplatin is dependent on the activity of XPF endonuclease. Clin Cancer Res 17(14):4731-41, 7/15/2011. e-Pub 6/1/2011. PMID: 21632856.
22. Liu Y, Lang F, Xie X, Prabhu S, Xu J, Sampath D, Aldape K, Fuller G, Puduvalli VK. Efficacy of adenovirally expressed soluble TRAIL in human glioma organotypic slice culture and glioma xenografts. Cell Death Dis 2(N/A):e121, 2011. e-Pub 2/24/2011. PMCID: PMC3101700.
23. Sampath D, Liu C, Vasan K, Sulda M, Puduvalli VK, Wierda WG, Keating MJ. Histone deacetylases mediate the silencing of miR-15a and miR-16 and miR-29b in chronic lymphocytic leukemia. Blood 119(5):1162-72, 2/2/2012. e-Pub 11/16/2011. PMID: 22096249.

Invited Articles
1. Ewald B, Sampath D, Plunkett W. Nucleoside analogs: molecular mechanisms signaling cell death. Oncogene 27(50):6522-37, 10/2008. PMID: 18955977.
2. Tili E, Michaille JJ, Gandhi V, Plunkett W, Sampath D, Calin GA. miRNAs and their potential for use against cancer and other diseases. Future Oncol 3(5):521-37, 10/2007. PMID: 17927518.
3. Sampath D, Rao VA, Plunkett W. Mechanisms of apoptosis induction by nucleoside analogs. Oncogene 22(56):9063-9074, 12/8/2003. PMID: 14663485.
4. Sampath D, Plunkett W. Design of new anti-cancer therapies targeting cell cycle checkpoint pathways. Curr Opin Oncol 13(6):484-490, 2001. PMID: 11673689.

Editorials
1. Sampath D, Calin GA. Coding and Non coding: The CLL mix. Blood 115(19):3858-9, 5/13/2010. PMID: 20466868.
2. Sampath D, Calin GA. miRs-Fine tuning prognosis in CLL. Blood 113(21):5035-36, 5/21/2009. PMID: 19470431.
3. Sampath D, Gandhi V. Dialing resistance up a Notch. Leuk Lymphoma 50(2):158, 2/2009. PMID: 19235014.

Abstracts
1. Sampath D, Du M, Keating M, Plunkett W. CLL response to DNA repair inhibition: Role for p53 and XIAP. Proceedings of the American Association for Cancer Research 46:780, 2005.
2. Liu X, Sampath D, Tseng J, Matsuda A, Gesner T, Plunkett W. Abrogation of S-phase and G2 cell cycle checkpoints by small molecule inhibitors of the DNA damage kinase, Chk1. Proceedings of the American Association for Cancer Research 46:396, 2005.
3. Puduvalli V, Xu J, Sampath D. Suberoylanilide hydroxamic acid (SAHA) induces G2 arrest and apoptosis in gliomas. Proceedings of the American Association for Cancer Research 46:424, 2005.
4. Sampath D, Du M, Keating MJ, Plunkett W. Fludarabine resistance in CLL is associated with non functional p53. Proceedings of the American Association for Cancer Research 47:884, 2006.
5. Ewald B, Sampath D, Plunkett W. Phosphorylation of H2AX in response to a gemcitabine-induced checkpoint: Increased phosphorylation subsequent to checkpoint abrogation. Proceedings of the American Association for Cancer Research 47:491, 2006.
6. Sampath D, Pudavalli V, Atadja P, Keating M Plunkett W. Histone deacetylase inhibitors activate p73 apoptotic responce in chronic lymphocytic. Proceedings of the American Association for Cancer Reaserch 48:967 (#4085), 2007.
7. Sampath D, Calin G, Pudavalli V, Gopisetty G, Taccioli C, Ewald B, Keating M, Plunkett W. MicroRNA 106b targets the ubiquitin ligase ITCH to enable the p73 apoptotic responce in chronic lymphocytic leukemia. Proceedings of the American Association for Cancer Research 49 (#234), 2008.
8. Sampath D. Chromatin modulation to target CLL. US European Alliance (#N/A), 2008.
9. Sampath D, Calin G, Pudavalli V, Gopisetty G, Taccioli C, Ewald B, Keating M, Plunkett W. Specific activation of microRNA 106b targets the ubiquitin ligase ITCH to enable the p73 apoptotic responce in chronic lymphocytic leukemia. EORTC-NCI-AACR Symposium on Molecular Targets and Cancer therapeutics (#249), 2008.

Book Chapters
1. Sampath D. Epigenetic regulation in CLL. In: Epigenetics of Leukemia. Springer: New York. In Press.
2. Sampath D. Role of microRNAs in leukemia. In: MicroRNA function in cancer. Springer. In Press.
3. Shi Z, Sampath D, Plunkett W. Therapeutic strategies that overcome resistance to nucleoside analogs: Dysregulating checkpoint response and survival pathways by UCN-01. In: Acute Leukemia IX. 41, 97-109, 2001.
4. Gandhi V, Estey EE, Seymour JF, Sampath D, Du M, Ayers M, Keating MJ, Plunkett W. Experimental Approaches and Novel Therapies. In: Modulation of Ara-C metabolism to improve AML response. Acute Leukemias VII, 577-583, 1997.

Letters to the Editor
1. Sampath D and Plunkett W. Context dependent expression of miR-106b in CLL. Blood 113(25):6499, 2009. PMID: N/A.

Grant & Contract Support

Title: Novel Pharmacologic Agent in CLL
Funding Source: NIH/NCI
Role: Co-Investigator
Principal Investigator: Thomas Kipps , Project 5 Leader- William Plunkett
Duration: 1/1/2012 - 12/31/2015
 
Title: The microRNA epigenome in CLL.
Funding Source: American Cancer Society (ACS)
Role: Principal Investigator
Duration: 1/1/2012 - 12/30/2015
 
Title: Epigenetic modulation of microRNA in CLL: Implications for therapeutic targeting
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 6/1/2010 - 5/31/2012
 
Title: Targeting epigenetically silenced microRNA pathways for the therapy of chronic lymphocytic leukemia
Funding Source: Ladies Leukemia League
Role: Principal Investigator
Duration: 7/1/2009 - 11/30/2010
 
Title: Chromatin Modulation as a Therapeutic Strategy for CLL
Funding Source: US-European Alliance for Chronic Lymphocytic leukemia
Role: Principal Investigator
Duration: 1/1/2008 - 12/31/2012
 
Title: MEMGEN ISF35 As an adjunct therapy in combination with chemo and biological therapies for the treatment of patients with B-cell malignancies
Funding Source: Memgen
Role: Principal Investigator
Duration: 1/9/2007 - 1/9/2008
 
Title: Transcriptional activation to target CLL
Funding Source: CLL Global Research Foundation
Role: Principal Investigator
Duration: 7/1/2006 - 7/30/2008

Last updated: 9/19/2012