Sham S. Kakar, Ph.D.
Professor of Physiology and Biophysics, Medical Onocology and of Biochemistry & Brown Cancer Center
Email Sham Kakar
Phone Number: (502) 852-0812 (Office)
Fax Number: (502) 852-2356
Address: 580 South Preston Street
Baxter II, Room 321E
University of Louisville
Louisville, KY 40202
Ph. D. 1983, Kurukshetra University, Karnal, India
- Professor, Department of Medicine
- Professor, Division of Medical Oncology
- Professor, Division of Endocrinology
- Senior Scientist, James Graham Brown cancer Center
- Associate professor, Department of Physiology and Biophysics
- Senior Scientist, IMD3
- Associate Professor, Department of Physiology and Biophysics
- Associate Professor, Department of Biochemistry and Molecular Biology
- Affiliated Assistant/Professor, Department of Animal and Dairy Sciences, Auburn University, Auburn, AL.
- Hormones and Cancer
- GnRH Receptors in Tumors
- Tumor transforming gene/PTTG
Sanjay Singh: Research Associate
Research Interests: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.
Selected Publications:Published Journals:
- Dinesh Abichandani, John Trent and Sham S. Kakar (2006) Molecular structure of gonadotropin-releasing hormone receptor and its alteration in hypogonadotropic hypogonnadism. In preapration.
- Sham S. Kakar. Identification of genes regulated by securin in human ovarian surface epithelial cells. In preparation. Invited paper.
- Tariq Hamid and Sham S. Kakar (2007) Protein kinase A (PKA) serves as a primary pathway in activation of Nur77 expression by gonadotropin releasing hormone (GnRH) in LßT2 cells. Submitted.
- 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.
- 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.
- 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. J Endocrinology. 194 (1): 179-191.
- Hanzhu Jin, Bin Hong, Sham S. Kakar and Kyung A Kang (2007) Tumor specific nano-entities for optical and hyperthermia treatment. Adv Exp Med Biol, Vol XXXVIII. In press.
- Sham S. Kakar, Hanzhu Jin, Bin Hong, John W. Eaton, Kyung A. Kang (2007) LHRH targeted therapy for breast cancer. Adv Exp Med Biol, Vol XXVIII. In press.
- C. Cristina, G.S. Diaz-Torga, R.G. Goya, S.S. Kakar SS, 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.
- Mohhamad T. Malik and Sham S. Kakar (2006) Regulation of angiogenesis and invasion by human pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Molecular Cancer. 5: 61.
- Sham S. Kakar and Mohammad T. Malik (2006) Suppression of lung cancer with siRNA targeting PTTG. Int J Oncology 29: 387-395.
- Williard Mazhawidza, Stephen J. Winters, Ursula B. Kaiser and Sham S. Kakar (2006) Identification of genes modulated by activin in LbT2 cells using DNA microarray analysis. Histol Histopath 21: 167-178.
- Alvin Thompson and Sham S. Kakar (2005) Insulin and IGF-1 regulate the expression of the pituitary tumor tnasforming gene (PTTG) in breast tumor cells. FEBS Let. 579: 3195-3200.
- Tariq Hamid, Tariq Malik and Sham S. Kakar (2005) Ectopic expression of PTTG1/securing promotes tumorigenesis in human embryonic kidney cells. Mol Cancer 4(1): 1-13.
- Tariq Hamid and Sham S. Kakar (2004) PTTG/securin activates expression of p53 and modulates its function. Molecular Cancer 3(18): 1-13.
- Amy Clem, Tariq Hamid and Sham S. Kakar (2003) Characterization of the role of Sp1 and NF-Y in differential regulation of PTTG/Securin expression in tumor cells. Gene. 322: 113-121.
- Yohei Okadam Akiko Murota-Kawano, Sham S. Kakar and Stephen J Winters (2003) Evidence that GnRH-II stimulates LH and FSH secretion from monkey pituitary cultures by activating the GnRH-1 receptor. Biol Reprod. 69: 1356-1361.
- Sham S. Kakar, Stephen J. Winters, Wolfgang Zacharias, Donald M. Miller and Shawn Flynn (2003) Identification of distinct gene expression profiles associated with treatment of LT2 cells with gonadotropin-releasing hormone agonist using cDNA microarray analysis. Gene. 308: 67-77.
- Sham S. Kakar, M. Tariq Malik and Stephen J. Winters (2002) Gonadotropin-releasing hormone receptor: cloning, expression and transcriptional regulation. Progress in Brain Research.141: 129-147.
- Sham S. Kakar, Leilei Chen, Rashmi Puri, Shawn E. Flynn and Lothar Jennes (2001) Characterization of a polyclonal antibody to human tumor transforming gene 1 (PTTG1) protein. J Histol Cytochem 49: 1537-1546.
- Rashmi Puri, Albert Tousson A, Leilei Chen and Sham S. Kakar (2001) Molecular cloning of pituitary transforming gene 1 (PTTG1) from ovarian tumors and its expression in tumors. Cancer Let 163: 131-139.
- Christi Bradshaw and Sham S. Kakar (2007) Pituitary Tumor Transforming Gene: An Important Gene in Normal Cellular Functions and Tumorigenesis. Histol Histopath. 22: 219-226.
- Sham S. Kakar, Tariq Malik, Stephen Winters and Williard Mazhawidza (2003). Gonadotropin-releasing hormone receptors: intracellular signaling transduction mechanisms, and downstream signaling genes. Vitamin and Hormones. 69: 151-207.
- Tariq Hamid and Sham S. Kakar (2003) PTTG and Cancer. Histol Histopathol. 18: 245-251.
- B. Hafez, Sham S. Kakar and S. Hafez (1999) Molecular biology of oviductal functions/gamete interaction. Adv. Reprod. III: 195-201.
- B. Hafez, Sham S. Kakar and S. Hafez (1999) Andropause/premenopause/menopause: pathophysiology/clinical parameters. Adv. Reprod. III: 179-185.
- S. Hafez, B. Hafez and Sham S. Kakar (1999) Andrology Research: physiology/clinical application. Adv. Reprod. III: 158-162.
- Sham S. Kakar (1999) Tumorigenesis of ovarian tumors. Adv Reprod. III: 311-324.
- Sham S. Kakar, Iantha Williams and Lothar Jennes (1999) Molecular physiology of the gonadotropin-releasing hormone (GnRH) receptor. Adv Reprod. III: 267- 278.
- Sham S. Kakar, I. Williams and B. Hafez (1999) Gonadotropin-releasing hormone receptor: molecular parameters. Adv Reprod. III: 143-146.
- Sham S. Kakar (1999) Molecular characterization of the gonadotropin-releasing hormone receptor gene. Adv Reprod. III: 59-80.