The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Kalpana Mujoo, Ph.D.

Kalpana Mujoo, Ph.D.

Assistant Professor, Center for Cell Signaling

Kalpana.Mujoo@uth.tmc.edu

713-500-2428

Dr. Mujoo received her undergraduate degree from Lucknow University and her doctoral degree in Biochemistry at the Central Drug Research Institute in India. She pursued her postdoctoral training at the Scripps Research Institute-La Jolla in the area of Biochemistry, Cancer Biology and Tumor Immunology under the mentorship of Dr. Ralph A. Reisfeld.  During her postdoctoral training she developed a number of monoclonal antibodies against well-characterized tumor associated antigens and anti-disialoganlioside GD2 antibody has been used in multi-center clinical trials for human neuroblastoma and melanoma in the USA and Germany.

During her term as a junior faculty member at the University of Texas M.D. Anderson Cancer Center, Dr. Mujoo was involved in conducting research in basic cancer biology and experimental therapeutics. She focused her efforts on elucidating the molecular mechanisms of various anti-cancer agents and studying their therapeutic potential in xenograft models of various tumor types. She conducted mechanistic, pharmacokinetic and therapeutic studies with immunotoxins, elucidated the molecular mechanism(s) of tumor suppressor gene p53 and conducted adenoviral mediated gene therapy of p53 tumor suppressor in an established ovarian cancer model. Dr. Mujoo isolated and characterized a novel plant compound triterpene glycoside and demonstrated that apoptosis induced by this compound was in part due to the inhibition PI3K/AKT pathway and transcription factor NFkB. She conducted studies on circumvention of cisplatin-induced drug resistance with a novel CDDP analog in human ovarian, breast and prostate cancer models.

Dr. Mujoo is a member of American Association for Cancer Research. She joined the Brown Foundation Institute of Molecular Medicine in October, 2004. She is also a faculty member of the Department of Integrative Biology and Pharmacology at the Medical School. Her current research focuses on delineating the role of nitric oxide (NO) and cyclic GMP signaling in proliferation, differentiation and self-renewal of mouse and human embryonic stem cells and adult mesenchymal stem cells and stem cell derived cardiomyocytes.  She is also interested in studying the cross-talk between NO and other signaling pathways such as PI3K/AKT, MAPK during the course of stem cell differentiation. Studies conducted in the laboratory have demonstrated the differential expression of various nitric oxide signaling components in undifferentiated and differentiated mouse and human ES and adult mesenchymal stem cells.  Using the activators and inhibitors of the NO/cGMP pathway, studies in the laboratory have also shown that NO donors, NOS inhibitors, sGC activators, PDE and PKG inhibitors influence the differentiation of ES cells into cardiomyocytes and proliferation of ES-derived cardiomyocytes.  In addition, her laboratory is interested in elucidating the role of NO signaling pathway in various human cancers. Preliminary studies have shown the differential expression and activity of NO receptor soluble guanylyl cyclase in breast, ovarian and prostate cancer cells. Future studies will focus on examining the role of NO/cGMP in transplantation stem cells and stem cell derived cardiomyocytes in various cardiovascular systems. In addition, studies on cell cycle regulation of stem cells and in depth evaluation of NO signaling components in proliferation/apoptosis and differentiation of stem cells and cancer cells. Human and mouse ES cells, MSC and cancer cell cultures and cell free preparations are used to characterize various regulatory pathways using biochemical, pharmacological and molecular biological approaches.

Selected Publications:

Sharin V, Mujoo, K, Kots A, Martin E, Murad F, Sharina I. Nitric oxide receptor soluble guanylyl cyclase undergoes splicing regulation in differentiating human embryonic stem cells.  Stem Cells and Development (In press), 2010

Mujoo K, Sloan C, Sharin V, Marin E, Nikonoff LE, Choi B-K, Kots A, Murad F. Role of soluble guanylyl cyclase- cyclic GMP signaling in tumor cell proliferation. Nitric Oxide: Biology and Chemistry 22: 43-50, 2010  

Mujoo K, Sharin V, Bryan N, Krumenacker JS, Sloan C, Parveen S, Kots A, Murad F.   Role of nitric oxide signaling components in differentiation of embryonic stem cells to myocardial cells.  Proc Natl Acad Sci USA, 105: 18924-18929, 2008

Mujoo K, Krumenacker JS, Wada Y, Murad F.  Differential expression of nitric oxide signaling components in undifferentiated and differentiated human embryonic stem cells.  Stem Cells Dev, 15: 779-787, 2006.

Mujoo K, Watanabe M, Khokhar AR, Siddik ZH. Increased sensitivity of a metastatic model of prostate cancer to a novel tetravalent platinum analog.  The Prostate 62: 91-100, 2005.

Mujoo K, Watanabe M, Nakamura J, Khokhar AR, Siddik ZH. Status of p53 phosphorylation and function in sensitive and resistant human cancer models exposed to platinum-based DNA damaging agents. J Cancer Res Clin Oncol 129: 709-718, 2003.

Mujoo K, Haridas V, Hoffmann JJ, Wachter GA, Hunter LK, Blake ME, Lu Y, Jayatilake G, Bailey D, Mills GB,  Gutterman JU. Triterpenoid saponins from Acacia Victoriae (Bentham) decrease tumor cell proliferation and induce apoptosis. Cancer Res 61: 5486-5490, 2001.

Haridas V, Higuchi M, Jayatilake G, Bailey D, Mujoo K, Gutterman JU. Avicins: Novel triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation. Proc Natl Acad Sci USA 98: 5821-5826, 2001.

Mujoo K, Zhang L, Klostergaard J, and Donato NJ.  Emergence of cisplatin- resistant cells from the OVCAR-3 ovarian carcinoma cell line with p53 mutations, altered tumorigenecity and increased apoptotic sensitivity to p53 gene replacement.    Int J Gynecol.Cancer 10: 105-114, 2000.

Mujoo K, Catino JC, Maneval DC, and Gutterman JU.  p53 induced growth inhibition and apoptosis with p53-adenoviral construct in human ovarian cancer.  Int J Gynecol Cancer. 8: 233-241, 1998.

Mujoo K., Maneval, D.C., Anderson, S.C., and Gutterman, J.U.  Adenoviral mediated p53 tumor suppressor gene therapy of human ovarian carcinoma.  Oncogene 12: 1617-1623, 1996.

Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, Kasi LP, Bhadkamkar V, Fritsche HA, Benjamin RS, Legha SS, Ater JL, Jaffe N, Itoh K, Ross MI, Bucana CD, Thompson L, Cheung L, and Rosenblum MG.  Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J of Clin Oncol 12: 184-193, 1994.

Mujoo K, Donato NJ, Lapushin R, Rosenblum MG, and Murray JL.  Tumor necrosis factor α and gamma-interferon enhancement of anti-epidermal growth factor receptor monoclonal antibody binding to human melanoma cells. J of Immunotherapy 13: 166-174, 1993.

Mujoo K, Rosenblum MG, and Murray JL. Augmented binding of radiolabeled monoclonal antibodies to melanoma cells using specific antibody combinations. Cancer Res 51: 2768-2772, 1991.

Mujoo K, Reisfeld RA, Cheung L, and Rosenblum MG.  A potent and specific immunotoxin for tumor cells expressing disialoganglioside GD2.  Cancer Immunol Immunother 34: 198-204, 1991.