Jyotsana Singhal, M.S.
Jyotsana Singhal was born in Agra, India, where she received her education, B.S. in 1988 and M.S. in 1990, from Agra University, Agra, India, and moved to USA in 1992. She was trained as a Lab Technician (1992 – 1995) with Prof. Bogdan Nowicki at the University of Texas Medical Branch (UTMB) at Galveston, TX, where she was promoted to Research Assistant (1996 – 1999). She joined the University of Texas at Arlington (UTA), Arlington, TX in 1999, where she was Research Associate. After that, she joined the University of North Texas Health Science Center (UNTHSC), Fort Worth, TX as Senior Research Associate in 2007, and later on she joined Beckman Research Institute of the City of Hope, National Medical Center, Duarte, CA, as Staff Scientist in 2012.
Her current research interests are in multi-drug resistance in cancer. Her research objectives and expertise are in: 1) Stress signaling and oxidative stress, 2) Carcinogenesis and chemoprevention, 3) intracellular immuno-staining and multicolor flow-cytometry, and 4) Syngeneic and xenografts model. She has published more than 50 peer-reviewed research articles in these and related areas.
Agra University, Agra, India, M.S., Chemistry
Agra University, Agra, India, B.S., Zoology, Botany, Chemistry
2016-present, Staff Scientist, Department of Molecular Medicine, Beckman Research Institute of City of Hope, National Medical Center, Duarte, CA
2012 - 2016, Staff scientist, Department of Diabetes Complications & Metabolism at City of Hope's Diabetes & Metabolism Research Institute, Duarte, CA
2007 - 2012, Senior research associate, Department of Molecular Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX
1999 - 2007, Research associate, Department of Chemistry and Biochemistry, University of Texas, Arlington, TX
1995- 1999, Research assistant, Department of Obstetrics-Gynecology, University of Texas Medical Branch, Galveston, TX
Our laboratory is interested in the interface of cell signaling and oxidative stress metabolism and its role in insulin-resistance and carcinogenesis.
We are working on COH-SR4 which has shown promising anticancer and antidiabetic effects in vitro and in vivo. COH-SR4 suppresses lipogenic genes like sterol regulatory element binding protein-1c (SREBF1), acetyl-Coenzyme A carboxylase (ACOACa), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), stearoyl-Coenzyme A desaturase 1 (SCD1), carnitine palmitoyltransferase 1a (CPT1a) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), as well as gluconeogenic genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) in the liver of obese mice. COH-SR4 inhibits cell cycle kinases, decreases vimentin and fibronectin, and activates AMPK pathway while inhibiting cancer progression. We have worked on the efficacy and mechanisms of the anticancer effects induced by 2’-hydroxyflavanone (2HF), didymin, and vicenin-2 in renal cancer, neuroblastoma and prostate cancers respectively. RLIP76 (Ral Binding Protein, RalBP1) is a 76 kDa multifunctional protein associated with carcinogenesis, metastases, drug- and radiation-resistance. We have also worked on mapping the critical upstream and downstream regulators of RLIP76 in multiple phases of tumor progression and therapeutic response.
American Association for Cancer Research (AACR)
Contribution to science
Investigating the cellular, signaling and metabolic basis for the observed effects of COH-SR4 in insulin-resistance and cancers
a. Singhal, S.S., Figarola, J., Singhal, J., Leake, K., Nagaprashantha, L., Lincoln, C., Gigiu, G., Horn, D., Jove, R., Awasthi, S. and Rahbar, S. (2012) 1,3-bis(3,5-dichlorophenyl) urea compound ‘COH-SR4’ inhibits proliferation and activates apoptosis in melanoma. Biochem Pharmacol 84: 1419-1427
b. Singhal SS, Figarola J, Singhal J, Nagaprashantha L, Berz, D., Rahbar S, and Awasthi S. (2013) Novel compound 1, 3-bis (3, 5-dichlorophenyl) urea inhibits lung cancer progression. Biochem Pharmacol 86: 1664-1672.
c. Figarola JL, Singhal J., Rahbar S., Awasthi S, and Singhal SS. (2014) LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells. Apoptosis 19: 776-788.
d. Figarola JL, Singhal J, Tompkins JD, Rogers GW, Warden C, Horne D, Riggs AD, Awasthi S, Singhal SS (2015) SR4 Uncouples Mitochondrial Oxidative Phosphorylation, Modulates AMP-dependent Kinase (AMPK)-Mammalian Target of Rapamycin (mTOR) Signaling, and Inhibits Proliferation of HepG2 Hepatocarcinoma Cells. J Biol Chem., 290: 30321–30341.
Mapping the scientific basis for the anticancer effects observed following targeted depletion and/inhibition of RLIP76, a stress-responsive, membrane associated, non-ATP binding cassette (ABC) multi-specific transporter of chemotherapeutic drugs as well as of glutathione-electrophiles conjugates (GS-E) in the Mercapturic Acid Pathway (MAP). Our studies have revealed that inhibiting or depleting RLIP76 leads to regression of multiple types of cancers like melanoma, neuroblastoma, colon, kidney, pancreas, and lung cancers in human xenografts, which signifies the essential role of RLIP76 in different types of cancers.
a. Singhal, S.S., Singhal, J., Sharma, R., Singh, S.V., Zimniak, P., Awasthi, Y.C., and Awasthi, S. (2003) Role of RLIP76 in lung cancer doxorubicin resistance: The ATPase activity of RLIP76 correlates with doxorubicin and 4-Hydroxynonenal resistance in lung cancer cells. Int J Oncol 22: 365-375.
b. Singhal SS, Yadav S, Singhal J, Zajac E, Drake K, Awasthi YC, and Awasthi S (2005) Depletion of RLIP76 sensitizes lung cancer cells to doxorubicin. Biochem Pharmacol 70: 481-488.
c. Stuckler, D., Singhal, J., Singhal, S.S., Yadav, S., Awasthi, Y.C. and Awasthi, S. (2005) RLIP76 Transports vinorelbine and mediates drug resistance in non-small cell lung cancer. Cancer Res 65: 991-998.
d. Singhal SS, Singhal J, Yadav S, Dwivedi S, Boor P, Awasthi YC and Awasthi S (2007) Regression of lung and colon cancer xenografts by depleting or inhibiting RLIP76 (RALBP1). Cancer Res. 67: 4382-4389
e. Singhal SS, Singhal J, Yadav S, Sahu M, Awasthi YC and Awasthi S (2009) RLIP76: A target for kidney cancer therapy. Cancer Res. 69: 4244-4251
f. Singhal, S.S., Yadav, S., Vatsyayan, R., Chaudhary, P., Borvak, J., Singhal, J. and Awasthi, S. (2009) Increased expression of Cdc2 inhibits transport function of RLIP76 and promotes apoptosis. Cancer Lett. 283: 152-158.
g. Singhal, J., Yadav, S., Singhal, S.S., Warnke, M., Yacoub, A., Dent, P., Sharma, R., Awasthi, Y.C., Armstrong, D. and Awasthi, S. (2008) Ralbp1 in defense of radiation poisoning. Int. J. Rad. Oncol. Biol. Phys. 72: 553-561.
h. Singhal, S.S., Wickramarachchi, D., Yadav, S., Singhal, J., Leake, K., Vatsyayan, R., Lelsani, P., Chaudhary, P., Suzuki, S., Yang, S., Awasthi, Y.C., and Awasthi, S. (2011) Glutathione-conjugate transport by RLIP76 is required for clathrin-dependent endocytosis and chemical carcinogenesis. Mol Cancer Therapeutics 10: 16-28.
i. Singhal J, Yadav S, Nagaprashantha L, Vatsyayan R, Singhal SS, and Awasthi S. (2011) Targeting p53 null neuroblastomas through RLIP76. Cancer Prev Res 4: 879-889.
j. Leake, K., Singhal, J., Nagaprashantha, L., Awasthi, S. and Singhal, S.S. (2012) RLIP76 regulates PI3K/Akt signaling and chemo-radio-therapy resistance in pancreatic cancer. PLoS ONE 7(4): e34582.
Assessment of the anti-diabetic effects and underlying mechanisms following depletion of RLIP76.
a. Awasthi, S., Singhal, S. S., Yadav, S., Singhal, J., Vatsyayan, R., Zajac, E., Luchowski, R., Borvak, J., Gryczynski, K. and Awasthi, Y C. (2010) A central role of RLIP76 in regulation of glycemic control. Diabetes 59: 714-725.
b. Singhal J, Nagaprashantha, L., Vatsyayan, R., Awasthi S, and Singhal SS. (2011) RLIP76, a glutathione-conjugate transporter, plays a major role in the pathogenesis of metabolic syndrome. PLoS ONE 6(9): e24688.
c. Singhal SS, Figarola J, Singhal J, Reddy MA, Liu X, Berz D, Natarajan R, and Awasthi S. (2013) RLIP76 protein knockdown attenuates obesity due to a high-fat diet. J Biol Chem 288: 23394-23406.
Investigation of the anticancer effects of flavonoids like 2´-hydroxyflavanone, vicenin, and didymin in chemoprevention studies on various cancers of kidney, lung, prostate and neuroblastomas.
a. Nagaprashantha, L., Vatsyayan, R., Singhal, J., Lelsani, P., Awasthi, Y.C., Prokai, L., Awasthi, S., and Singhal, SS. (2011) 2-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL mutant renal cell carcinoma. Carcinogenesis 32: 568-575.
b. Nagaprashantha LD, Vatsyayan R, Singhal J, Fast, S., Roby, R., Awasthi, S., and Singhal, S.S. (2011) Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer. Biochem Pharmacol 82: 1100-1109.
c. Singhal J, Nagaprashantha L, Vatsyayan R, Ashutosh, Awasthi S, and Singhal SS. (2012) Didymin induces apoptosis by inhibiting N-Myc and up regulating RKIP in neuroblastoma. Cancer Prev Res 5: 473-483.
d. Nagaprashantha, L., Talamantes, T., Singhal, J., Guo, J., Vatsyayan, R., Rauniyar, N., Awasthi, S., Singhal, S.S., Prokai, L. (2013) Proteomic analysis of signaling networks regulation in renal cell carcinoma with differential hypoxia-inducible factor-2α expression. PLoS ONE 8(8): e71654.
Investigation of the early stages of bacterial invasion with a well-characterized bacterial ligand and host receptor.
a. Nowicki B., Fang L., Singhal J., Nowicki S., Yallampalli C.(1997) Lethal outcome of uterine infection in pregnant but not in nonpregnant rats and increased death rate with inhibition of nitric oxide . Am J Reprod Immunol 38: 309-12.
b. Nowicki B., Singhal J., Fang L., Nowicki S., Yallampalli C. (1999). Inverse relationship between severity of experimental pyelonephritis and nitric oxide production in C3H/HeJ mice. Infect Immun 67: 2421-7.
c. Goluszko P., Selvarangan R., Popov V., Pham T., Wen JW., Singhal J. (1999) Decay-accelerating factor and cytoskeleton redistribution pattern in HeLa cells infected with recombinant Escherichia coli strains expressing Dr family of adhesions. Infect Immun 67: 3989-97.
d. Selvarangan R., Goluszko P., Popov V., Singhal J., Pham T., Lublin DM., Nowicki S., Nowicki B.(2000) Role of decay-accelerating factor domains and anchorage in internalization of Dr-fimbriated Escherichia coli. Infect Immun 68: 1391-9.