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Kumudha Balakrishnan, M.Sc., M. Phil., 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

Bio Statement

My research at MD Anderson is focused on identifying novel therapeutic agents for the treatment of leukemia, in particular for CLL, by understanding the metabolism, mechanism of action, and interactions with other therapies. The goal is to implement new agents in the clinic for the treatment of CLL.  Understanding the molecular pathways involved in the action of chemotherapeutic agents is important in designing new clinical protocols for use in the clinical setting. Multiple clinical trials have been initiated at MD Anderson based on encouraging preclinical data obtained by me and my colleagues.  Many chemotherapeutic agents display efficacy in preclinical studies. However, their activity varies to a greater extent in clinical settings. For CLL cells, bone marrow or lymph node microenvironments have greater influence on the evolution of the leukemic phenotype. Therefore, my interest is to understand the therapeutic response in presence of microenvironment and its association with clinical stage and prognosis.

Research Interests

Office Address

The University of Texas MD Anderson Cancer Center
1901 East Road
Unit Number: 1950
Houston, TX 77054
Room Number: 4SCR3.1040
Phone: (713) 563-6975
Fax: (713) 794-4316
Email: kbalakr@mdanderson.org

Education & Training

Degree-Granting Education

2001 A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India, PHD, Clinical Biochemistry
1992 A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India, M.Phil, Biochemistry
1991 A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India, MS, Biochemistry
1989 University of Madras, Vaishnav College for Women, Chromepet, Chennai, India, BS, Chemistry

Postgraduate Training

7/2002-2/2007 Postdoctoral Fellowship, Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, Dr. Varsha Gandhi

Experience/Service

Academic Appointments

Assistant Professor, Faculty member of Experimental Therapeutics Academic program (ETAP), The University of Texas Health Science Center, Houston, TX, 2011
Assistant Professor, Faculty member of Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX, 2010
Instructor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 3/2007-8/2010
Assistant Professor, Department of Biochemistry, H.R. D. Degree and PG College, Osmania University, Hyderabad, Andhra Pradesh, India, 6/1998-6/2000
Lecturer, Department of Biochemistry, Vinayaka Mission Dental College, Salem, Tamil Nadu, India, 12/1992-12/1993

Other Appointments/Responsibilities

Senior Biochemist, Sharp Diagnostics, Chennai, India, 12/1993-10/1994

Honors and Awards

2012 Junior Research Faculty Citation of Excellence Winner, Division of Cancer Medicine
2005-2006 Shannon Timmins Post-Doctoral Fellowship Award

Professional Memberships

American Association for Cancer Research (AACR)
Associate Member, 2002-present
American Society of Hematology
member, 2012-present
Faculty 1000
member, 2012-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Patel V, Balakrishnan K, Wierda WG, Gandhi V. Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia. Leukemia & Lymphoma. In Press.
2. S Faderl, K Balakrishnan, DA Thomas, F Ravandi, G Borthakur, J Burger, A Ferrajoli, J Cortes, S O’Brien, T Kadia, J Feliu, W Plunkett, V Gandhi, HM Kantarjian. Phase 1 and Extension Study of Clofarabine plus Cyclophosphamide in Patients with Relapsed /Refractory Acute Lymphoblastic Leukemia (ALL). Clin Lymphoma Myeloma Leuk. In Press.
3. Phillip CJ, Zaman S, Shentu S, Balakrishnan K, Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, Stellrecht, CM and Gandhi V. Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines. Journal of Hematology & Oncology. In Press.
4. Sandoval MR, Balakrishnan K, Luthra R, Keating M, Gandhi V. DNA Repair Initiation Induces Expression of Ribonucleotide Reductase in Human Chronic Lymphocytic Leukemia Cells. Leuk Lymphoma. e-Pub 6/17/2013. PMID: 23772636.
5. Balakrishnan K, Ravandi F, Bantia S, Franklin A, Gandhi V. Preclinical and Clinical Evaluation of Forodesine in Pediatric and Adult B-Cell Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. e-Pub 6/14/2013. PMID: 23773454.
6. Balakrishnan K, Aggarwal S, Wierda W, Gandhi V. Bax and Bak are required for apogossypolone, a BH3-mimetic, induced apoptosis in chronic lymphocytic leukemia cells. Leuk Lymphoma. e-Pub 8/6/2012. PMID: 22866921.
7. Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 119(5):1182-9, 2/2/2012. e-Pub 12/16/2011. PMID: 22180443.
8. Kuang Y, Balakrishnan K, Gandhi V, Peng X. Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs. J Am Chem Soc 133(48):19278-81, 12/7/2011. e-Pub 11/10/2011. PMCID: PMC3265938.
9. Balakrishnan K, Burger JA, Quiroga MP, Henneberg M, Ayres ML, Wierda WG, Gandhi V. Influence of bone marrow stromal microenvironment on forodesine induced responses in CLL primary cells. Blood 116(7):1083-91, 8/19/2010. e-Pub 5/4/2010. PMCID: PMC2938131.
10. Balakrishnan K, Verma D, O'Brien S, Kilpatrick JM, Chen Y, Tyler BF, Bickel S, Bantia S, Keating MJ, Kantarjian H, Gandhi V, Ravandi F. Phase 2 and pharmacodynamic study of oral forodesine in patients with advanced, fludarabine-treated chronic lymphocytic leukemia. Blood 116(6):886-92, 8/12/2010. e-Pub 4/28/2010. PMCID: PMC2924226.
11. Dennison JB, Balakrishnan K, Gandhi V. Preclinical activity of 8-chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis. Br J Haematol 147(3):297-307, 11/2009. e-Pub 8/2009. PMID: 19709085.
12. Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jager U, Gandhi V, Kay NE, Plunkett W, Burger JA. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood, 9/2009. e-Pub 9/2009. PMID: 19762485.
13. Quiroga MP, Balakrishnan K, Kurtova AV, Sivina M, Keating MJ, Wierda WG, Gandhi V, Burger JA. B cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel Syk inhibitor, R406. Blood 114(5):1029-37, 7/2009. e-Pub 6/2009. PMID: 19491390.
14. Balakrishnan K, Wierda WG, Keating MJ, Gandhi V. Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood 112(5):1971-80, 9/2008. e-Pub 6/2008. PMCID: PMC2518898.
15. Balakrishnan K, Burger JA, Wierda W and Gandhi V. AT-101 induces apoptosis in CLL B-cells and overcomes stromal cell mediated Mcl-1 induction and drug resistance. Blood 113(1):149-53, 2008. e-Pub 9/2008. PMCID: PMC2614629.
16. Karp JE, Ricklis RM, Balakrishnan K, Briel J, Greer J, Gore SD, Smith BD, McDevitt MA, Carraway H, Levis MJ, Gandhi V. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. Blood 110(6):1762-9, 9/2007. e-Pub 6/2007. PMCID: PMC1976362.
17. Balakrishnan K, Nimmanapalli R, Keating MJ, Ravandi F, Gandhi V. Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells. Blood 108(7):2392-8, 5/2006. e-Pub 6/2006. PMCID: PMC1895565.
18. Balakrishnan K, Wierda WG, Keating MJ, Gandhi V. Mechanisms of cell death of chronic lymphocytic leukemia lymphocytes by RNA-directed agent, 8-NH2-adenosine. Clin Cancer Res 11(18):6745-52, 9/2005. PMID: 16166456.
19. Balakrishnan K, Stellrecht CM, Genini D, Ayres M, Wierda WG, Keating MJ, Leoni LM, Gandhi V. Cell death of bioenergetically compromised and transcriptionally challenged CLL lymphocytes by chlorinated ATP. Blood 105(11):4455-62, 6/2005. e-Pub 2/2005. PMCID: PMC1895042.

Invited Articles

1. Balakrishnan K, Gandhi V. Bcl-2 antagonists: a proof of concept for CLL therapy. Invest New Drugs 31(5):1384-94, 10/2013. e-Pub 8/2013. PMID: 23907405.
2. Balakrishnan K, Gandhi V. Uncoupling Endoplasmic Reticulum Stress and Autophagy: A Potential Implication for CLL Therapy. Leuk Lymphoma. e-Pub 5/9/2013. PMID: 23656199.
3. Gandhi V, Balakrishnan K. CCL2 in chronic lymphocytic leukemia: a macro in microenvironment? Leuk Lymphoma 53(10):1849-50, 10/2012. e-Pub 5/2012. PMID: 22563818.
4. Balakrishnan K, Gandhi V. Protein Kinases: Emerging therapeutic targets in chronic lymphocytic leukemia. Expert Opin Investig Drugs 21(4):409-23, 4/2012. e-Pub 3/2012. PMID: 22409342.
5. Balakrishnan K, Gandhi V. The micros in harmony: microRNA and microenvironment. Leuk Lymphoma 52(9):1626-9, 9/2011. e-Pub 7/11/2011. PMID: 21740342.
6. Chen LS, Balakrishnan K, Gandhi V. Inflammation and survival pathways: Chronic lymphocytic leukemia as a model system. Biochem Pharmacol 80(12):1936-45, 12/15/2010. e-Pub 8/7/2010. PMID: 20696142.
7. Gandhi V, Balakrishnan K and Chen LS. MCL-1: The 1 in CLL. Blood 112(9):3538-40, 11/2008. e-Pub 8/2008. PMID: 18948586.
8. Gandhi V, Balakrishnan K. Forodesine- A T-Cell targeted therapeutic. Semin Oncol 34(6 Suppl 5):S8-12, 12/2007. e-Pub 2007. PMID: 18086347.

Abstracts

1. Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG, Keating MJ, Faia K, O’Brien S, Kutok JL, McGovern K, Gandhi V. Inhibition of PI3K-δ and -γ Isoforms by IPI-145 in Chronic Lymphocytic Leukemia Overcomes Signals from PI3K/AKT/S6 Pathway and Promotes Apoptosis. American Society of Hematology. e-Pub 12/2013.
2. Pierce DW, Balakrishnan K, Gandhi V, Heise C, Nacht M, Aslanian S, Liu X, Hong S, Wu S, Zavodovskaya M, Marine J, Barnett E, Nava-Parada P, Mei J, Chopra R, Burger JA, Singh J. The Covalent Bruton’s Tyrosine Kinase (Btk) Inhibitor CC-292 Blocks the Survival of CLL Cells In Vitro and Leads to Rapid-Onset Lymphocytosis in CLL Patients. American Soceity of Hematology, 12/2013.
3. Nacht M, Evans E, Ponader S, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O’Brien S, Singh J, Pierce DW, Heise C, Barnett E, Marine J, Nava-Parada P, Mei J, Chopra R, Burger JA. The Covalent Bruton’s Tyrosine Kinase Inhibitor CC-292 Blocks the Survival of CLL Cells In Vitro and Leads to Rapid-Onset Lymphocytosis in CLL Patients. iWCLL. e-Pub 8/2013.
4. Veerati T, Gandhi V, Balakrishnan K. Targeting Nitric Oxide Production in Mantle Cell Lymphoma (MCL). King Foundation Program, 6/2013.
5. Sarkar A, Chen J, Balakrishnan K and Gandhi V. L14R8, a Pac-1 derivative induce casapase-3 mediated apoptosis in mantle cell lymphoma. American Association of Cancer Research. e-Pub 4/2013.
6. Patel V, Wierda WG, Balakrishnan K, Gandhi V. Novel caspase-3 activator, L14R8, induces apoptosis in chronic lymphocytic leukemia cells. American Association of Cancer Research. e-Pub 4/2013.
7. Balakrishnan K, Fu M, Onida F, Wierda W, Keating M and Gandhi V. Role of smac-mimetic in restoring apoptosis in chronic lymphocytic leukemia. American Association of Cancer Research. e-Pub 4/2013.
8. Wierda W.G, Balakrishnan K, Ferrajoli A, Kadia T, Cortes JE, O'Brien S, Burger JA, Tambaro FP, Jalayer A, Lerner S, Keating MJ and Gandhi V. A Phase I/II Trial of Fludarabine, Bendamustine, and Rituximab (FBR) Chemoimmunotherapy for previously Treated Patients with CLL. American Society of Hematology. e-Pub 12/2012.
9. Patel V, Chen LS, Wierda WG, Balakrishnan K, Gandhi V. Impact of bone marrow microenvironment on 93 apoptotic pathway target mRNA expression in CLL cells. iwCLL. e-Pub 8/2012.
10. Chen J, Sarkar A, Balakrishnan K and Gandhi V. Caspase activator L14R8 induces apoptosis in Mantle cell lymphoma cells. e-Pub 7/2012.
11. Patel V, Chen LS, Wierda WG, Balakrishnan K, Gandhi V. Impact of bone marrow microenvironment on 93 apoptotic pathway target mRNA expression in CLL cells. American Association of Cancer Research. e-Pub 4/2012.
12. Balakrishnan K, Fu M, Onida F, Wierda W, Keating M and Gandhi V. Restoration of Smac-mediated apoptosis in chronic lymphocytic leukemia. American Association of Cnacer Research. e-Pub 4/2012.
13. Wierda W.G, Balakrishnan K, Ferrajoli A, Kadia T, Cortes JE, O'Brien S, Burger JA, Tambaro FP, Jalayer A, Lerner S, Keating MJ and Gandhi V. A Phase I/II Trial of Fludarabine, Bendamustine, and Rituximab (FBR) Chemoimmunotherapy for previously Treated Patients with CLL. American Society of Hematology 118. e-Pub 11/2011.

Grant & Contract Support

Title: “Biochemistry of Apoptosis in CLL”
Funding Source: NIH/NCI
Role: Co-Investigator
Duration: 5/1/2012 - 4/30/2017
 
Title: Restoration of Smac-Mediated Apoptosis in Chronic lymphocytic leukemia
Funding Source: CLL Global Research Foundation
Role: Principal Investigator
Duration: 4/1/2012 - 3/31/2014
 
Title: Targeting Nitric Oxide Production for CLL therapy
Funding Source: CTT
Role: Co-Investigator
Principal Investigator: Gandhi
Duration: 1/11/2012 - 1/11/2013
 
Title: "Pim Kinase Inhibition as a Therapeutic Strategy for AML"
Funding Source: Leukemia and Lymphoma Society
Role: Co-Investigator
Duration: 10/1/2010 - 9/30/2013

Last updated: 12/19/2013