Sham S. Kakar, Ph. D.
Professor, Department of Physiology and Biophysics
580 South Preston Street
Baxter II, Room 321E
University of Louisville
Louisville, KY 40202
- Member Division of Medical Onocology
- Professor of Biochemistry & Molecular Genetics
- Professor, Division of Endocrinology and Metabolism
- Professor, James Graham Brown Cancer Center
- Member, Institute for Molecular Diversity and Drug Design (IMD3), University of Louisville
- Member, Center for Genetics and Molecular Medicine (CGeMM)
- Ph. D. 1983, Kurukshetra University, Karnal, India
Laboratory Team Members:
Sanjay Singh, Research Associate
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.
- Abdelbaset-Ismail A, Pedziwiatr D, Suszyńska E, Sluczanowska-Glabowska S, Schneider G, Kakar SS, Ratajczak MZ. Vitamin D3 stimulates embryonic stem cells but inhibits migration and growth of ovarian cancer and teratocarcinoma cell lines. J Ovarian Res. 2016 Apr 18;9:26. PubMed PMID: 27091127; PubMed Central PMCID: PMC4835879.
- Macha MA, Rachagani S, Pai P, Gupta S, Lydiatt WM, Smith RB, Johansson SL, Lele SM, Kakar SS, Farghaly H, Lee JH, Meza J, Ganti AK, Jain M, Batra SK. MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway. Oncogene. 2015 May 21;34(21):2814. PubMed PMID: 25994150.
- Mierzejewska K, Borkowska S, Suszynska E, Suszynska M, Poniewierska-Baran A, Maj M, Pedziwiatr D, Adamiak M, Abdel-Latif A, Kakar SS, Ratajczak J, Kucia M, Ratajczak MZ. Hematopoietic stem/progenitor cells express several functional sex hormone receptors-novel evidence for a potential developmental link between hematopoiesis and primordial germ cells. Stem Cells Dev. 2015 Apr 15;24(8):927-37. PubMed PMID: 25607657; PubMed Central PMCID: PMC4390002.
- Gunjal PM, Schneider G, Ismail AA, Kakar SS, Kucia M, et al. Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy. J Ovarian Res. 2015 Mar 28;8:20. PubMed PMID: 25887079; PubMed Central PMCID: PMC4425926.
- Macha MA, Rachagani S, Pai P, Gupta S, Lydiatt WM, Smith RB, Johansson SL, Lele SM, Kakar SS, Farghaly H, Lee JH, Meza J, Ganti AK, Jain M, Batra SK. MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway. Oncogene. 2015 Mar 26;34(13):1698-708. PubMed PMID: 24747969; NIHMSID: NIHMS591176; PubMed Central PMCID: PMC4205229.
- Kakar SS, Kakar C. Generation of transgenic mouse model using PTTG as an oncogene. Methods Mol Biol. 2015;1267:395-411. PubMed PMID: 25636481.
- Gunjal P, Pedziwiatr D, Ismail AA, Kakar SS, Ratajczak MZ. An emerging question about putative cancer stem cells in established cell lines-are they true stem cells or a fluctuating cell phenotype?. J Cancer Stem Cell Res. 2015;3PubMed PMID: 26925434; NIHMSID: NIHMS728114; PubMed Central PMCID: PMC4767173.
- Beach A, Zhang HG, Ratajczak MZ, Kakar SS. Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J Ovarian Res. 2014 Jan 25;7:14. PubMed PMID: 24460816; PubMed Central PMCID: PMC3932023.
- Suszynska M, Poniewierska-Baran A, Gunjal P, Ratajczak J, Marycz K, Kakar SS, Kucia M, Ratajczak MZ. Expression of the erythropoietin receptor by germline-derived cells - further support for a potential developmental link between the germline and hematopoiesis. J Ovarian Res. 2014;7:66. PubMed PMID: 24982693; PubMed Central PMCID: PMC4074848.
- Kakar SS, Ratajczak MZ, Powell KS, Moghadamfalahi M, Miller DM, et al. Withaferin a alone and in combination with cisplatin suppresses growth and metastasis of ovarian cancer by targeting putative cancer stem cells. PLoS One. 2014;9(9):e107596. PubMed PMID: 25264898; PubMed Central PMCID: PMC4180068.
- Ratajczak MZ, Jadczyk T, Schneider G, Kakar SS, Kucia M. Induction of a tumor-metastasis-receptive microenvironment as an unwanted and underestimated side effect of treatment by chemotherapy or radiotherapy. J Ovarian Res. 2013 Dec 27;6(1):95. PubMed PMID: 24373588; PubMed Central PMCID: PMC3880975.
- Fong MY, McDunn J, Kakar SS. Metabolomic profiling of ovarian carcinomas using mass spectrometry. Methods Mol Biol. 2013;1049:239-53. PubMed PMID: 23913221.