Houston Methodist. Leading Medicine.
Houston Methodist. Leading Medicine

Kapil N. Bhalla M.D.

Kapil N. Bhalla, M.D.

Kapil N. Bhalla, M.D.


Full Member
Medical and Scientific Director of the Cockrell Center for Advanced Therapeutics
Co-Director of Phase I Clinical Research Unit
Cancer Research Program
The Methodist Hospital Research Institute

E-mail: knbhalla@houstonmethodist.org
Phone: 713-441-9022


Education

M.D.   Maulana Azad Medical College, University of Delhi, New Delhi, India
 

Postdoctoral Training

Internship, Pathology, St. Michael’s Medical Center, Newark, N.J.

Internship/Residency, Internal Medicine, St. Michael’s Medical Center, Newark, N.J.

Fellowship, Hematology/Oncology, Columbia University College of Physicians & Surgeons, New York, N.Y.

 

Biography

Dr. Bhalla is a graduate of the University of Delhi’s Maulana Azad Medical College in India. Dr. Bhalla completed internships in pathology and internal medicine and a residency in internal medicine at St. Michael’s Medical Center in Newark, NJ.  Following a postdoctoral fellowship in hematology and oncology, he was appointed assistant professor of medicine at Columbia University College of Physicians and Surgeons in New York. He later served as a Professor on the faculty of the Medical University of South Carolina, Emory University, University of Miami and University of South Florida.

Dr. Bhalla served as the deputy director of the University of Kansas Cancer Center, where he was also a professor of internal medicine, and honored with the Schutte/Speas Endowed Chair in Hematologic Malignancies. He also served as the chief of the personalized cancer medicine initiative at the Kansas University Cancer Center and was an eminent scholar of the Kansas Bioscience Authority. Prior to this, he served as the founding director of the Medical College of Georgia Cancer Center, where he occupied the Cecil F. Whitaker, Jr., M.D. Chair in Cancer. He was also a Georgia Research Alliance Eminent Scholar in Cancer and the Georgia Cancer Coalition’s Distinguished Cancer Scholar. He joined The Methodist Hospital Research Institute in 2013 as the scientific and medical director of the Cockrell Center for Advanced Therapeutics and co-director of the Phase I Clinical Research Unit.

Dr. Bhalla is Board-certified in internal medicine, hematology and medical oncology. He is also a member of the American Society of Clinical Oncology, American Society of Hematology, and the American Association for Cancer Research.  He has served as the chair of the neoplasia and subsequently of the lymphoid neoplasia committee of the American Society of Hematology. He is currently the track leader of tumor biology for the American Society of Clinical Oncology.

He is a past recipient of the American Cancer Society’s Career Development Award and the Leukemia & Lymphoma Society of America’s Fellow and Scholar Awards. Dr. Bhalla is a former member of the National Institutes of Health’s experimental therapeutics II study section (1993 to 1997), and the former chairperson of the developmental therapeutics study section (2005 to 2007). He is currently a member of the basic mechanisms of cancer therapy study section of NIH, as well as a member of the translational research study section of the Leukemia and Lymphoma Society.

He is the author of more than 195 scholarly articles on cancer research, and serves as the senior editor of Molecular Cancer Therapeutics and a member of the editorial boards of Clinical Cancer Research, Cancer Biology and Therapy, Molecular Cancer and PLoS One. Dr. Bhalla’s current laboratory and clinical research, supported by multiple NCI grants, includes cancer epigenetics, chaperone biology, and novel targeted therapies for leukemia and cancer.

Description of Research

Dr. Bhalla’s basic-translation-clinical research comprises the biology, molecular pharmacology and mechanisms involving the actions of novel anti-leukemia and anti-breast cancer agents, utilizing in vitro and in vivo cultured and primary models of leukemia and breast cancer. Specifically, this research is focused on elucidating the role of Heat Shock Factor 1 and its target molecular chaperones, including the heat shock proteins (hsp) hsp90, hsp70 and GRP78. For Acute Myeloid Leukemia (AML), the focus is also on the biologic activity and therapeutic targeting of Nucleophosmin 1 (NPM1), another known molecular chaperone. This involves determining the domain structure and binding partners of NPM1, as well as developing high throughput screening assays for identifying novel anti-NPM1 agents for anti-leukemia and anti-lymphoma therapy. Dr. Bhalla’s research also includes targeting molecular chaperones to abrogate the levels and activity of the client oncoproteins in myeloid leukemia and lymphoid malignancies. Both in the laboratory and in the clinic, Dr. Bhalla has evaluated the biologic effects and anti-leukemia activity of novel agents that target ß-catenin, epimutations and epigenetic mechanisms, including histone deacetylases (HDAC3 & 6 and SIRT2), histone methyl transferases (EZH2), histone demethylase (LSD1) and the bromodomain containing BET protein BRD4. Additionally, he has found that HDAC6 regulates the acetylation status of specific lysine residues on hsp90, hsp70 and GRP78, which controls their chaperone function. How modulating the activity of these molecular chaperones affects the level and function of multiple client oncoproteins (ex. JAK2V617F, BCR-ABL, FLT3, AKT, MEK) that are required  for the growth and survival of transformed cells has been the focus of Dr. Bhalla’s translational research. This has lead to the discovery of candidate combination therapies involving targeted agents with associated potential predictive biomarkers of efficacy, which are currently under evaluation in clinical trials.

Major Areas of Research

Cancer, epigenetics, chaperone biology, developmental therapeutics of hematologic malignancies, precision medicine

Recent Publications

Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK, Wang HG, Bhalla KN. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6841-6. PMID: 23569248

Fiskus W, Verstovsek S, Manshouri T, Smith JE, Peth K, Abhyankar S, McGuirk J, Bhalla KN. Dual PI3K/AKT/mTOR Inhibitor BEZ235 Synergistically Enhances the Activity of JAK2 Inhibitor against Cultured and Primary Human Myeloproliferative Neoplasm Cells. Mol Cancer Ther. 2013 May;12(5):577-88. PMID: 23445613

Zhang X, Zhao X, Fiskus W, Lin J, Lwin T, Rao R, Zhang Y, Chan JC, Fu K,Marquez VE, Chen-Kiang S, Moscinski LC, Seto E, Dalton WS, Wright KL, Sotomayor E, Bhalla K, Tao J. Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas. Cancer Cell. 2012 Oct 16;22(4):506-23. PMID: 23079660

Fiskus W, Rao R, Balusu R, Ganguly S, Tao J, Sotomayor E, Mudunuru U, Smith JE, Hembruff SL, Atadja P, Marquez VE, Bhalla K. Superior efficacy of a combined epigenetic therapy against human mantle cell lymphoma cells. Clin Cancer Res. 2012 Nov 15;18(22):6227-38. PMID: 22932665

Rao R, Balusu R, Fiskus W, Mudunuru U, Venkannagari S, Chauhan L, Smith JE, Hembruff SL, Ha K, Atadja P, Bhalla KN. Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts superior efficacy against triple-negative human breast cancer cells. Mol Cancer Ther. 2012 Apr;11(4):973-83. PMID: 22367781.

Fiskus W, Verstovsek S, Manshouri T, Rao R, Balusu R, Venkannagari S, Rao NN, Ha K, Smith JE, Hembruff SL, Abhyankar S, McGuirk J, Bhalla KN. Heat shock protein 90 inhibitor is synergistic with JAK2 inhibitor and overcomes resistance to JAK2-TKI in human myeloproliferative neoplasm cells. Clin Cancer Res. 2011 Dec 1;17(23):7347-58. PMID: 21976548

Balusu R, Fiskus W, Rao R, Chong DG, Nalluri S, Mudunuru U, Ma H, Chen L, Venkannagari S, Ha K, Abhyankar S, Williams C, McGuirk J, Khoury HJ, Ustun C, Bhalla KN. Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1. Blood. 2011 Sep 15;118(11):3096-106. PMID: 21719597

Ha K, Fiskus W, Rao R, Balusu R, Venkannagari S, Nalabothula NR, Bhalla KN. Hsp90 inhibitor-mediated disruption of chaperone association of ATR with hsp90 sensitizes cancer cells to DNA damage. Mol Cancer Ther. 2011 Jul;10(7):1194-206. PMID: 21566061

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Mandawat A, Fiskus W, Buckley KM, Robbins K, Rao R, Balusu R, Navenot JM, Wang ZX, Ustun C, Chong DG, Atadja P, Fujii N, Peiper SC, Bhalla K. Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists. Blood. 2010 Dec 9;116(24):5306-15. PMID: 20810927

Rao R, Nalluri S, Fiskus W, Savoie A, Buckley KM, Ha K, Balusu R, Joshi A, Coothankandaswamy V, Tao J, Sotomayor E, Atadja P, Bhalla KN. Role of CAAT/enhancer binding protein homologous protein in panobinostat-mediated potentiation of bortezomib-induced lethal endoplasmic reticulum stress in mantle cell lymphoma cells. Clin Cancer Res. 2010 Oct 1;16(19):4742-54. PMID: 20647473