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Rajan Singh, PhD
Title Associate Professor
Faculty Rank Associate Professor
Degree PhD
Institution Charles R. Drew University of Medicine and Science
Department Internal Medicine
Clusters College of Medicine
Address
1731 E. 120th Street, Hawkins Building
1731 E. 120th Street, Hawkins Building
City Los Angeles
State CA
Postal Code 90059
Telephone (323) 563-5828
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Email
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Awards and Honors icon

2003 NIH/NIGMS MBRS SCORE
2003 American Federation of Medical Research Outsatnding Young Investigator Award
2004 American Federation of Medical Research GlaxoSmith Cline Scholar Award
2004 National Institute on Aging (Co-Investigator) R01DK070534
2006 Endocrine Society, USA Endocrine Society Travel Award
2008 11th RCMI International Symposium RCMI Travel Award
2008 National Institute on Aging (Principal Investigator) SC1AG033407
2009 LSI, Charles R. Drew University Emerging Scientist Award
2009 National Institute on Aging (Principal Investigator) SC1AG033407-ARRA Suppl
2010 Western Society of Clinical Investigation WSCI Travel Award
2014 National Institute on Aging (Principal Investigator) 9SC1AG049682

Narrative icon

  Research Goal 1: One of my research goals is to elucidate the molecular targets responsible for cell fate determination in mesenchymal precursor cells and understand how sex steroids regulate overall body composition. We have identified follistatin (Fst) as a novel molecular target of testosterone. Currently, we are investigating signal transduction pathways involved in this process using Fst overexpressing mice and mouse embryonic fibroblasts (MEFs) isolated from mice with various genetic backgrounds such as Fst-/-, Fst+/+ and Mst-/- to understand the molecular basis of androgen/Fst regulation of body composition. My research goal is to establish a stem-cell model to investigate the role of various anabolic steroids and screen selective androgen receptor modulators (SARMs) for their potential to regulate cell fate. These findings have considerable clinical implications because of the health implications of obesity and loss of muscle mass in aging men. These studies have the potential to eliminate the unwanted side effects of testosterone associated with supra-physiological doses required for increased muscle mass and function, such as increase in prostate specific antigen (PSA); as low physiological doses of testosterone can be used in combination with physiological doses of follistatin or inhibitors of histone deacetylase (HDAC). These studies may provide rationale for clinical trial of the proposed combination therapy to achieve cost-effective and beneficial effects on sarcopenia or HIV-infection normally associated with muscle loss and frailty in minority population. Research Goal 2: Female breast cancer incidence and mortality rate significantly varies by race/ethnicity. African American (AA) women suffer from most aggressive type of triple negative (TN) breast tumors and are more likely to die compared to other ethnic groups. It has been suggested that differences in the tumor microenvironment in AA patients such as increased infiltration of tumor-associated macrophages (TAMs) and increased number of mammary cancer stem cells (MCSCs) contribute to the aggressive behavior of these tumors. Arginine is utilized mainly by two metabolic pathways called nitric oxide synthase (NOS) and arginase pathways. Utilization of arginine by arginase pathway in TAMs is critical for the survival of tumor cells. Mammary cancer stem cells (MCSCs) have been implicated in the initiation and progression of breast cancer and are resistant to most therapeutic agents. However, the metabolic requirements of these cells are not known. Based on our preliminary findings, we hypothesize that TAMs and MCSCs, two key cell types implicated in aggressive tumor behavior in TN AA patients are dependent on arginase pathway for their survival and self-renewal respectively. In order to test our hypothesis, we are inhibiting arginase expression in MCSCs obtained from TN AA tumors to test whether this can inhibit the aggressive behavior of tumor using nude mice model. My other goal is to identify key metabolic requirements of these specialized cell types (TAMs and MCSCs) in the tumor micro-environment.

Programs, Membership, and Biomedical Research icon

Community Faculty Status Non-Community Faculty

NIH Awarded Grants icon

  Research projects funded by the National Institutes of Health (NIH), the Centers for Disease Control (CDC), the Food and Drug Administration (FDA), and the Department of Veterans Affairs (VA)

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1.
2017Follistatin promotes browning and influences energy metabolism5SC1AG049682-08
2.
2016Follistatin promotes browning and influences energy metabolism5SC1AG049682-07
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2015Follistatin promotes browning and influences energy metabolism5SC1AG049682-06
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2014Follistatin promotes browning and influences energy metabolism9SC1AG049682-05
5.
2011Role of Follistatin during Androgen Regulation of Body Composition5SC1AG033407-04
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2010Role of Follistatin during Androgen Regulation of Body Composition5SC1AG033407-03
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2009Role of Follistatin during Androgen Regulation of Body Composition5SC1AG033407-02
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2009Role of Follistatin during Androgen Regulation of Body Composition3SC1AG033407-02S1
9.
2008Role of Follistatin during Androgen Regulation of Body Composition1SC1AG033407-01A1

Publications icon

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1. Pervin S, Singh V, Tucker A, Collazo J, Singh R. Modulation of transforming growth factor-ß/follistatin signaling and white adipose browning: therapeutic implications for obesity related disorders. Horm Mol Biol Clin Investig. 2017 Sep 09; 31(2).
2. Singh R, Braga M, Reddy ST, Lee SJ, Parveen M, Grijalva V, Vergnes L, Pervin S. Follistatin targets distinct pathways to promote brown adipocyte characteristics in brown and white adipose tissues. Endocrinology. 2017 Jan 16.
3. Martinez L, Thames E, Kim J, Chaudhuri G, Singh R, Pervin S. Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis. BMC Cancer. 2016; 16(1):559.
4. Pervin S, Singh R, Parveen M, Basgen JM, Fazel S, Meshesha MF, Thames EC, Moore B, Martinez L, Howard CB, Vergnes L, Reue K. Increased expression of beige/brown adipose markers from host and breast cancer cells influence xenograft formation in mice. Mol Cancer Res. 2015 Oct 13.
5. Singh R, Braga M, Pervin S. Regulation of brown adipocyte metabolism by myostatin/follistatin signaling. Front Cell Dev Biol. 2014; 2:60.
6. Braga M, Reddy ST, Vergnes L, Pervin S, Grijalva V, Stout D, David J, Li X, Tomasian V, Reid CB, Norris KC, Devaskar SU, Reue K, Singh R. Follistatin promotes adipocyte differentiation, browning, and energy metabolism. J Lipid Res. 2014 Mar; 55(3):375-84.
7. Jasuja R, Costello JC, Singh R, Gupta V, Spina CS, Toraldo G, Jang H, Li H, Serra C, Guo W, Chauhan P, Narula NS, Guarneri T, Ergun A, Travison TG, Collins JJ, Bhasin S. Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate-sparing anabolic therapy. Aging Cell. 2014 Apr; 13(2):303-10.
8. Singh R, Avliyakulov NK, Braga M, Haykinson MJ, Martinez L, Singh V, Parveen M, Chaudhuri G, Pervin S. Proteomic identification of mitochondrial targets of arginase in human breast cancer. PLoS One. 2013; 8(11):e79242.
9. Braga M, Pervin S, Norris K, Bhasin S, Singh R. Inhibition of in vitro and in vivo brown fat differentiation program by myostatin. Obesity (Silver Spring). 2013 Jun; 21(6):1180-8.
10. Srivastava A, Mishra A, Singh R, Rai R, Srivastava N, Mittal B. Multi-analytic approach elucidates significant role of hormonal and hepatocanalicular transporter genetic variants in gallstone disease in North Indian population. PLoS One. 2013; 8(4):e59173.
11. Pervin S, Tran L, Urman R, Braga M, Parveen M, Li SA, Chaudhuri G, Singh R. Oxidative stress specifically downregulates survivin to promote breast tumour formation. Br J Cancer. 2013 Mar 5; 108(4):848-58.
12. Pervin S, Hewison M, Braga M, Tran L, Chun R, Karam A, Chaudhuri G, Norris K, Singh R. Down-regulation of vitamin D receptor in mammospheres: implications for vitamin D resistance in breast cancer and potential for combination therapy. PLoS One. 2013; 8(1):e53287.
13. Braga M, Bhasin S, Jasuja R, Pervin S, Singh R. Testosterone inhibits transforming growth factor-ß signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action. Mol Cell Endocrinol. 2012 Mar 5; 350(1):39-52.
14. Kumar R, Zakharov MN, Khan SH, Miki R, Jang H, Toraldo G, Singh R, Bhasin S, Jasuja R. The dynamic structure of the estrogen receptor. J Amino Acids. 2011; 2011:812540.
15. Pervin S, Tran A, Tran L, Urman R, Braga M, Chaudhuri G, Singh R. Reduced association of anti-apoptotic protein Mcl-1 with E3 ligase Mule increases the stability of Mcl-1 in breast cancer cells. Br J Cancer. 2011 Jul 26; 105(3):428-37.
16. Pervin S, Chaudhuri G, Singh R. NO to breast: when, why and why not? Curr Pharm Des. 2010; 16(4):451-62.
17. Singh R, Bhasin S, Braga M, Artaza JN, Pervin S, Taylor WE, Krishnan V, Sinha SK, Rajavashisth TB, Jasuja R. Regulation of myogenic differentiation by androgens: cross talk between androgen receptor/ beta-catenin and follistatin/transforming growth factor-beta signaling pathways. Endocrinology. 2009 Mar; 150(3):1259-68.
18. Gupta V, Bhasin S, Guo W, Singh R, Miki R, Chauhan P, Choong K, Tchkonia T, Lebrasseur NK, Flanagan JN, Hamilton JA, Viereck JC, Narula NS, Kirkland JL, Jasuja R. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008 Dec 16; 296(1-2):32-40.
19. Pervin S, Tran AH, Zekavati S, Fukuto JM, Singh R, Chaudhuri G. Increased susceptibility of breast cancer cells to stress mediated inhibition of protein synthesis. Cancer Res. 2008 Jun 15; 68(12):4862-74.
20. Pervin S, Singh R, Chaudhuri G. Nitric oxide, N omega-hydroxy-L-arginine and breast cancer. Nitric Oxide. 2008 Sep; 19(2):103-6.
21. Artaza JN, Singh R, Ferrini MG, Braga M, Tsao J, Gonzalez-Cadavid NF. Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts. J Endocrinol. 2008 Feb; 196(2):235-49.
22. Pervin S, Singh R, Hernandez E, Wu G, Chaudhuri G. Nitric oxide in physiologic concentrations targets the translational machinery to increase the proliferation of human breast cancer cells: involvement of mammalian target of rapamycin/eIF4E pathway. Cancer Res. 2007 Jan 1; 67(1):289-99.
23. Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, Bhasin S. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology. 2006 Jan; 147(1):141-54.
24. Jasuja R, Catlin DH, Miller A, Chang YC, Herbst KL, Starcevic B, Artaza JN, Singh R, Datta G, Sarkissian A, Chandsawangbhuwana C, Baker M, Bhasin S. Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats. Endocrinology. 2005 Oct; 146(10):4472-8.
25. Jasuja R, Ramaraj P, Mac RP, Singh AB, Storer TW, Artaza J, Miller A, Singh R, Taylor WE, Lee ML, Davidson T, Sinha-Hikim I, Gonzalez-Cadavid N, Bhasin S. Delta-4-androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men. J Clin Endocrinol Metab. 2005 Feb; 90(2):855-63.
26. Pervin S, Singh R, Freije WA, Chaudhuri G. MKP-1-induced dephosphorylation of extracellular signal-regulated kinase is essential for triggering nitric oxide-induced apoptosis in human breast cancer cell lines: implications in breast cancer. Cancer Res. 2003 Dec 15; 63(24):8853-60.
27. Bhasin S, Taylor WE, Singh R, Artaza J, Sinha-Hikim I, Jasuja R, Choi H, Gonzalez-Cadavid NF. The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J Gerontol A Biol Sci Med Sci. 2003 Dec; 58(12):M1103-10.
28. Pervin S, Singh R, Chaudhuri G. Nitric-oxide-induced Bax integration into the mitochondrial membrane commits MDA-MB-468 cells to apoptosis: essential role of Akt. Cancer Res. 2003 Sep 1; 63(17):5470-9.
29. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003 Nov; 144(11):5081-8.
30. Singh R, Pervin S, Chaudhuri G. Caspase-8-mediated BID cleavage and release of mitochondrial cytochrome c during Nomega-hydroxy-L-arginine-induced apoptosis in MDA-MB-468 cells. Antagonistic effects of L-ornithine. J Biol Chem. 2002 Oct 4; 277(40):37630-6.
31. Singh R, Pervin S, Wu G, Chaudhuri G. Activation of caspase-3 activity and apoptosis in MDA-MB-468 cells by N(omega)-hydroxy-L-arginine, an inhibitor of arginase, is not solely dependent on reduction in intracellular polyamines. Carcinogenesis. 2001 Nov; 22(11):1863-9.
32. Kaminker JS, Singh R, Lebestky T, Yan H, Banerjee U. Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development. Development. 2001 Jul; 128(14):2639-48.
33. Pervin S, Singh R, Gau CL, Edamatsu H, Tamanoi F, Chaudhuri G. Potentiation of nitric oxide-induced apoptosis of MDA-MB-468 cells by farnesyltransferase inhibitor: implications in breast cancer. Cancer Res. 2001 Jun 15; 61(12):4701-6.
34. Shah S, Nathan L, Singh R, Fu YS, Chaudhuri G. E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy. Am J Physiol Regul Integr Comp Physiol. 2001 May; 280(5):R1546-54.
35. Pervin S, Singh R, Chaudhuri G. Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): potential role of cyclin D1. Proc Natl Acad Sci U S A. 2001 Mar 13; 98(6):3583-8.
36. Shah S, Hobbs A, Singh R, Cuevas J, Ignarro LJ, Chaudhuri G. Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves. Am J Physiol Regul Integr Comp Physiol. 2000 Oct; 279(4):R1478-85.
37. Singh R, Pervin S, Karimi A, Cederbaum S, Chaudhuri G. Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells. Cancer Res. 2000 Jun 15; 60(12):3305-12.
38. Singh R, Pervin S, Shryne J, Gorski R, Chaudhuri G. Castration increases and androgens decrease nitric oxide synthase activity in the brain: physiologic implications. Proc Natl Acad Sci U S A. 2000 Mar 28; 97(7):3672-7.
39. Nathan L, Pervin S, Singh R, Rosenfeld M, Chaudhuri G. Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo : possible mechanisms for gender differences in atherosclerosis. Circ Res. 1999 Aug 20; 85(4):377-85.
40. Pervin S, Singh R, Rosenfeld ME, Navab M, Chaudhuri G, Nathan L. Estradiol suppresses MCP-1 expression In vivo : implications for atherosclerosis. Arterioscler Thromb Vasc Biol. 1998 Oct; 18(10):1575-82.
41. Zhang RS, Guth PH, Scremin OU, Singh R, Pervin S, Chaudhuri G. Regulation of endometrial blood flow in ovariectomized rats: assessment of the role of nitric oxide. Am J Physiol. 1997 Oct; 273(4 Pt 2):H2009-17.
42. Singh R, Pervin S, Rogers NE, Ignarro LJ, Chaudhuri G. Evidence for the presence of an unusual nitric oxide- and citrulline-producing enzyme in rat kidney. Biochem Biophys Res Commun. 1997 Mar 27; 232(3):672-7.
43. Buga GM, Singh R, Pervin S, Rogers NE, Schmitz DA, Jenkinson CP, Cederbaum SD, Ignarro LJ. Arginase activity in endothelial cells: inhibition by NG-hydroxy-L-arginine during high-output NO production. Am J Physiol. 1996 Nov; 271(5 Pt 2):H1988-98.
44. Nair TM, Madhusudan K, Nagaraja V, Kulkarni BD, Majumdar HK, Singh R. Theoretical permutation gel electrophoretic analysis of a curved DNA fragment located in circular permutation. Electrophoresis. 1996 Apr; 17(4):633-41.
45. Singh R, Siddiqui KA, Valenzuela MS, Majumder HK. Kinetoplast DNA minicircle binding proteins in a Leishmania Spp: interference of protein DNA interaction by berenil. Indian J Biochem Biophys. 1995 Dec; 32(6):437-41.
46. Nair TM, Madhusudan K, Nagaraja V, Kulkarni BD, Majumdar HK, Singh R. On the mobility behavior of a curved DNA fragment located in circular permutation. FEBS Lett. 1994 Sep 12; 351(3):321-4.
47. Bhattacharyya R, Singh R, Hazra TK, Majumder HK. Application of polymerase chain reaction with specific and arbitrary primers to identification and differentiation of Leishmania parasites. FEMS Microbiol Lett. 1993 Nov 15; 114(1):99-104.

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1. Rajan Singh. Compositions and methods for treating or preventing metabolic syndrome disorders. 2017.

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