Sham S. Kakar, Ph.D.
Department of Physiology and Biophysics,
Department of Medicine,
Department of Biochemistry and Molecular Biology,
Division of Endocrinology and Metabolism,
Division of Medical Oncology,
and James Graham Brown cancer Center.
Cancer, Drug Discovery and Molecular Mechanisms of Disease
Our major/main research interest is to understand the molecular mechanism of causation and prevention of hormone related cancers. Drug investigation and the membrane signaling transduction mechanism in the regulation of cellular functions. We are working on two research projects: 1) Development of Targeted Therapy for Cancer Treatment. The primary treatment modality for cancer is cytoreductive surgery followed by adjuvant chemotherapy, radiotherapy, or both. This strategy is successful in the majority of patients, however it is always accompanied by cytotoxicity to normal organ and tissues and multidrug resistance (MDR). Ideally, therapeutic agents should be selectively targeted to cancerous cells to avoid systemic toxicities. Such targeting may be effected by forming an adduct between a cytotoxic agent and a tumor-specific ligand. Our work extends this adduct paradigm to studies of nanoparticles (NPs) targeted to the luteinizing hormone-releasing hormone (LHRH) receptor, which is overexpressed in variety of cancers. We hypothesize that targeting the LHRH receptor using LHRH and doxorubicin-conjugated (DOX) gold NPs will enhance particle uptake by cancer cells and lead to selective tumor cell killing without related systemic cytotoxicity. 2) Molecular mechanisms of pituitary tumor transforming gene (PTTG) in human tumorigenesis. PTTG is a potent oncogene and is found to be highly expressed in most of the tumors analyzed to date. Its overespression in normal cells leads to cellular transformation and development of tumors in nude mice. Our research work is focused to understand the mechanisms, by which PTTG mediates its tumorigenic function, determine the three dimensional structure and utilize PTTG as a target gene in the development of specific small molecules to target PTTG gene for the treatment of cancer.
C. Cristina, G.S. Diaz-Torga, R.G. Goya, S.S. Kakar, M.I. Perez-Millan, V. Q. Passos and D. Giannella-Neto D (2007) Bronstein MD. Becu-Villalobos D. PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Molecular Cancer 6: 4.
Shahenda M. El-Naggar, Mohhamad T. Malik, Alvin Martin, Joseph P. Moore, Marry Proctor, Tariq Hamid and Sham S. Kakar (2007) Development of cystic glandular hyperplasia of the endometrium in MISIIR-PTTG transgenic mice. Journal of Endocrinology 194 (1): 179-191.
Shahenda El-Naggar, Mohammed T. Malik and Sham S. Kakar (2007). Small interfering RNA against PTTG: A novel therapy for ovarian cancer. International Journal of oncology. 31(1): 137-143.
Stephen J. Winters, Dushan Ghooray, Yasuhisa Fusii, Joseph P. Moore Jr, Jennifer R. Nevitt and Sham S. Kakar (2007) GnRH activates follistatin through cyclic AMP signaling. Molecular and Cellular Endocrinology 271(1,2): 45-54.
Sham S. Kakar, Hanzhu Jin, Bin Hong, John W. Eaton, Kyung A. Kang (2008). LHRH targeted therapy for breast cancer. Adv Exp Med Biol. 614: 285-296.
Hanzhu Jin, Bin Hong, Sham S. Kakar and Kyung A Kang (2008) Tumor specific nano-entities for optical and hyperthermia treatment. Adv Exp Med Biol, 614: 275-284.
Siva K. Panguluri and Sham S. Kakar (2008) Identification of differentially expressed molecular markers for breast cancer diagnosis by cDNA-RAPD. Current Trends in Biotechnology and Pharmacy 2: 158-171.
Siva K. Panguluri and Sham S. Kakar (2008). PTTG1 (pituitary tumor-transforming 1). Atlas Genet Cytogenet Oncol Haematol. March 2008. URL http:AtlasGeneticsOncology.org/Genes/PTTG1ID41943ch5q35.html
Tariq Hamid and Sham S. Kakar (2008) Protein kinase A (PKA) serves as a primary pathway in activation of Nur77 expression by gonadotropin releasing hormone (GnRH) in LßT2 cells. International Journal of Oncology. In press.
Katherine M. Pohlgrees, Siva K. Panguluri and Sham S. Kakar (2008) Implication of nanoparticles in diagnosis and treatment of cancer: The future of oncology. In Cell Death and Cancer. Ed. Alakananda Basu; Research Signpost. In press.
Siva K. Panguluri and Sham S. Kakar (2008) Securin: An important gene in cellular functions and ovarian cancer. Review. Journal of Ovarian Research. In press.