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Kapil Mehta, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Experimental Therapeutics, Cancer Medicine (Biochemistry), The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor of Graduate School of Biomedical Sciences, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX

Research Interests

Inflammation-induced drug resistance and metastasis  

Development of resistance to chemotherapy and their dissemination to distant organs (metastasis) pose major challenge in successful treatment of cancer. In an attempt to understnd the nature of tumor-encoded genes whose expression contributes to the development of drug resistance and metastasis, we identified a stress responsive gene (TGM2) whose expression is upregulated in multiple drug resistant and metastatic tumors. TGM2 encodes a structurally and functionally complex protein (TG2), whose expression under physiological conditions implicated in cell migration  apoptosis, and angiogenesis during inflammation and would healing.  In cancer cells, aberrant TG2 expression is associated with poor drug response, increased metastatic potential, and poor patient survival. Its expression in epithelial cancer cells results in constitutive activation of cell growth and cell survival signaling pathways, transdifferentiation into mesenchymal cells (EMT) and acquisition of stem cell traits (CSC). Conversely, inhibition of TG2 by small-molecule inhibitors, antisense, ribozyme or small interfering RNA (siRNA) inhibited the tumor cell growth and invasiveness and rendered cancer cells sensitive to chemotherapy both in vitro and in animal models. The immediate objectives of our laboratory is to define TG2-regulated pathways that contribute to the development of drug resistance and metastasis in cancer cells. We believe that silencing of TG2 can deprive cancer cells of critical survival pathways and thus, TG2 represents an attractive therapeutic target for cancers in which TG2 is overexpressed. Indeed as a proof of concept we showed that downregulation of TG2 by liposomal siRNA could inhibit the dissemination and render orthotopically growing tumors sensitive to chemotherapy. 

Other areas of research interest in the lab 

Liposomes (lipid-vesicles) as drug delivery systems, integrin-mediated signaling pathways, retinoids (vitamin A and synthetic analogs) as differentiation-inducing agents

Office Address

The University of Texas MD Anderson Cancer Center
1901 East Road
Unit Number: 1950
Houston, TX 77054
Room Number: 4SCR3.1006
Phone: (713) 792-2649
Fax: (713) 745-4167
Email: kmehta@mdanderson.org

Education & Training

Degree-Granting Education

1981 Postgraduate Institute of Medical Education and Research, Chandigarh, India, PHD, Biochemistry
1976 Panjab University, Chandigarh, India, MS, Honors, Biochemistry

Selected Publications

Peer-Reviewed Original Research Articles

1. Wang D, Veena MS, Stevenson K, Tang C, Ho B, Suh JD, Duarte VM, Faull KF, Mehta K, Srivatsan ES, Wang MB. Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma In vitro and in Xenografts through the Inhibition of Nuclear Factor {kappa}B by an AKT-Independent Pathway. Clin Cancer Res 14(19):6228-6236, 10/1/2008. PMID: 18829502.
2. Hwang JY, Mangala LS, Fok JY, Lin YG, Merritt WM, Spannuth WA, Nick AM, Fiterman DJ, Vivas-Mejia PE, Deavers MT, Coleman RL, Lopez-Berestein G, Mehta K, Sood AK. Clinical and biological significance of tissue transglutaminase in ovarian carcinoma. Cancer Res 68(14):5849-58, 7/15/2008. PMCID: PMC2547344.
3. Verma A, Guha S, Diagaradjane P, Kunnumakkara AB, Sanguino AM, Lopez-Berestein G, Sood AK, Aggarwal BB, Krishnan S, Gelovani JG, Mehta K. Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer. Clin Cancer Res 14(8):2476-83, 4/15/2008. PMID: 18413840.
4. Verma A, Guha S, Wang H, Fok JY, Koul D, Abbruzzese J, Mehta K. Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells. Clin Cancer Res 14(7):1997-2005, 4/1/2008. PMID: 18381937.
5. Verma A, Wang H, Manavathi B, Fok JY, Mann AP, Kumar R, Mehta K. Increased expression of tissue transglutaminase in pancreatic ductal adenocarcinoma and its implications in drug resistance and metastasis. Cancer Res 66(21):10525-33, 11/2006. PMID: 17079475.
6. Mangala LS, Fok JY, Zorrilla-Calancha IR, Verma A, Mehta K. Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells. Oncogene 26(17):2459-70, 10/2006. PMID: 17043648.
7. Mann AP, Verma A, Sethi G, Manavathi B, Wang H, Fok JY, Kunnumakkara AB, Kumar R, Aggarwal BB, Mehta K. Overexpression of Tissue Transglutaminase Leads to Constitutive Activation of Nuclear Factor-{kappa}B in Cancer Cells: Delineation of a Novel Pathway. Cancer Res 66(17):8788-95, 9/2006. PMID: 16951195.
8. Fok JY, Ekmekcioglu S, Mehta K. Implications of tissue transglutaminase expression in malignant melanoma. Mol Cancer Ther 5(6):1493-503, 6/2006. PMID: 16818508.
9. Herman JF, Mangala LS, Mehta K. Implications of increased tissue transglutaminase (TG2) expression in drug-resistant breast cancer (MCF-7) cells. Oncogene 25(21):3049-58, 5/2006. PMID: 16449978.

Invited Articles

1. Mehta K, Kumar A, Kim HI. Transglutaminase 2: A multi-tasking protein in the complex circuitry of inflammation and cancer. Biochem Pharmacol 80(12):1921-1929, 12/2010. e-Pub 6/2010. PMID: 20599779.

Last updated: 11/4/2013