Sham S. Kakar, Ph.D.


Sham S. Kakar, Ph.D.
sskaka01@louisville.edu
Kurukshetra University
1983

Professor
Department of Physiology,
Department of Biochemistry and Molecular Biology,
Division of Endocrinology and Metabolism,
and Brown Cancer Center.

Research

Drug Discovery, Molecular Mechanisms of Cancer, and Cancer-Induced Cardiac Cachexia

My team research interest is to understand the molecular mechanism of causation and prevention of hormone related cancers, ovarian cancer. Drug investigation and the membrane signaling transduction mechanism in the regulation of cellular functions. We are working on three 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 affected 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 overexpression 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. 3) Cancer affects several organs in the body. Major effects are observed in skeletal muscle and cardiac muscle leading to loss of muscle mass resulting in muscle cachexia and cardiac cachexia. Our research is focused to understand the mechanisms of induction of cachexia especially cardiac cachexia and how it can be reversed to ameliorate cancer induced cardiac cachexia to avoid cardiac dysfunction.

Recent Publications

  1. Saha S, Singh PK, Roy P, Kakar SS. Cardiac Cachexia: Unaddressed Aspect in Cancer Patients. Cells. 2022 Mar 14;11(6):990.
  2. Haldar S, Agrawal H, Saha S, Straughn AR, Roy P, Kakar SS. Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells. Int J Biol Sci. 2022 Jan 1;18(2):675-692.
  3. Kakar SS, Ratajczak MZ. Commentary: FSH and various forms of FSH receptors: distribution and their functions in gonads and extra-gonadal tissues. J Ovarian Res. 2021 Oct 30;14(1):146.
  4. Kakar SS, Ratajczak MZ. Paper of October Issue of Stem Cell Reviews and Reports Presents a Novel View on Oogenesis in Adult Mammalian Ovaries. Stem Cell Rev Rep. 2021 Oct;17(5):1519-1520.
  5. Saha S, Parte S, Roy P, Kakar SS. Ovarian Cancer Stem Cells: Characterization and Role in Tumorigenesis. Adv Exp Med Biol. 2021; 1330:151-169.
  6. Saha S, Roy P, Corbitt C, Kakar SS. Application of Stem Cell Therapy for Infertility. Cells. 2021 Jun 28;10(7):1613.
  7. Straughn AR, Kelm NQ, Kakar SS. Withaferin A and Ovarian Cancer Antagonistically Regulate Skeletal Muscle Mass. Front Cell Dev Biol. 2021 Feb 25; 9:636498.
  8. Agrawal H, Das N, Nathani S, Saha S, Saini S, Kakar SS, Roy P. An Assessment on Impact of COVID-19 Infection in a Gender Specific Manner. Stem Cell Rev Rep. 2021 Feb;17(1):94-112.
  9. Zuber E, Schweitzer D, Allen D, Parte S, Kakar SS. Stem Cells in Ovarian Cancer and Potential Therapies. Proc Stem Cell Res Oncog. 2020 May;8: e1001.
  10. Saha S, Chakrabarti S, Singh PK, Poddar J, Satapathi S, Saini S, Kakar SS, Roy P. Physiological Relevance of Angiotensin Converting Enzyme 2 As a Metabolic Linker and Therapeutic Implication of Mesenchymal Stem Cells in COVID-19 and Hypertension. Stem Cell Rev Rep. 2021 Feb;17(1):132-143.
  11. Kelm NQ, Straughn AR, Kakar SS. Withaferin A attenuates ovarian cancer-induced cardiac cachexia. PLoS One. 2020 Jul 28;15(7): e0236680.
  12. Straughn AR, Kakar SS. Withaferin A: a potential therapeutic agent against COVID-19 infection. J Ovarian Res. 2020 Jul 19;13(1):79.
  13. Straughn AR, Kakar SS. Withaferin A ameliorates ovarian cancer-induced cachexia and proinflammatory signaling. J Ovarian Res. 2019 Nov 25;12(1):115.
  14. Parte S, Virant-Klun I, Patankar M, Batra SK, Straughn A, Kakar SS. PTTG1: a Unique Regulator of Stem/Cancer Stem Cells in the Ovary and Ovarian Cancer. Stem Cell Rev Rep. 2019 Dec;15(6):866-879.
  15. Udoh K, Parte S, Carter K, Mack A, Kakar SS. Targeting of Lung Cancer Stem Cell Self-Renewal Pathway by a Small Molecule Verrucarin J. Stem Cell Rev Rep. 2019 Aug;15(4):601-611.
  16. Ratajczak MZ, Domingues A, Suman S, Straughn AR, Kakar SS, Suszynska M. Novel view of the adult stem cell compartment - a developmental story of germline and parental imprinting. Proc Stem Cell Res Oncog. 2019;7: e1001.
  17. Abdelbaset-Ismail A, Cymer M, Borkowska-Rzeszotek S, Brzeźniakiewicz-Janus K, Rameshwar P, Kakar SS, Ratajczak J, Ratajczak MZ. Bioactive Phospholipids Enhance Migration and Adhesion of Human Leukemic Cells by Inhibiting Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS) in a p38 MAPK-Dependent Manner. Stem Cell Rev Rep. 2019 Feb;15(1):139-154.
  18. Parte SC, Batra SK, Kakar SS. Characterization of stem cell and cancer stem cell populations in ovary and ovarian tumors. J Ovarian Res. 2018 Aug 18;11(1):69.
  19. Bliss SA, Paul S, Pobiarzyn PW, Ayer S, Sinha G, Pant S, Hilton H, Sharma N, Cunha MF, Engelberth DJ, Greco SJ, Bryan M, Kucia MJ, Kakar SS, Ratajczak MZ, Rameshwar P. Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment. Sci Rep. 2018 Jan 10;8(1):367.
  20. Carter K, Rameshwar P, Ratajczak MZ, Kakar SS. Verrucarin J inhibits ovarian cancer and targets cancer stem cells. Oncotarget. 2017 Oct 6;8(54):92743-92756.
  21. Kakar SS, Parte S, Carter K, Joshua IG, Worth C, Rameshwar P, Ratajczak MZ. Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells. Oncotarget. 2017 Aug 10;8(43):74494-74505.
  22. Parte SC, Smolenkov A, Batra SK, Ratajczak MZ, Kakar SS. Ovarian Cancer Stem Cells: Unraveling a Germline Connection. Stem Cells Dev. 2017 Dec 15;26(24):1781-1803.
  23. Schneider G, Sellers ZP, Bujko K, Kakar SS, Kucia M, Ratajczak MZ. Novel pleiotropic effects of bioactive phospholipids in human lung cancer metastasis. Oncotarget. 2017 Apr 27;8(35):58247-58263.
  24. Kakar SS, Worth CA, Wang Z, Carter K, Ratajczak M, Gunjal P. DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer. J Cancer Stem Cell Res. 2016;4: e1002.
  25. 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.