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Indrani Sinha-Hikim, PhD

TitleAssociate Professor
InstitutionCharles R. Drew University of Medicine and Science
DepartmentInternal Medicine
Address1731 E. 120th Street
Los Angeles CA 90059
Phone(323) 563-5959
FaxNot Available
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    1. Cardiac consequences of prenatal cocaine exposure: The central hypotheses of the proposal are: i) that prenatal cocaine exposure induces cardiac myocyte apoptosis through activation of JNK/p38 MAPK-mediated mitochondria-dependent pathway and ii) minocycline, through inhibition of this signal transduction pathway, will confer protection in cardiac myocyte death induced by prenatal cocaine exposure. Specific aims contain characterization of the key molecular components of the JNK/p38-mediated apoptotic pathway in myocyte death and its mitigation by minocycline or JNK inhibitor. Results of this study will provide insight into the underlying mechanism of cardiac myocyte death that occurs in offspring after prenatal cocaine exposure. Identifying signaling pathways leading to myocyte death paves the way to design therapeutic remedies to myocyte death and, in turn, cardiac consequences of prenatal cocaine exposure.

    2. Molecular Mechanism of Sarcopenia and its Prevention: Sarcopenia is defined as the progressive decline of skeletal muscle mass and strength, which occurs with aging. I was able to show for the first time that testosterone-induced increase in muscle size is associated with fiber hypertrophy and significant increases in myonuclear and satellite cell numbers in both young and old men (Sinha-Hikim et al., Am J Physiol Endocrinol Metab 2002, 2003; Sinha-Hikim et al., J Clin Endocrinol Metab 2006). My laboratory, using mouse models, has provided new insights into the molecular mechanisms of muscle cell apoptosis (Sinha-Hikim et al, Apoptosis, 2007; Braga et al., Apoptosis, 2008). We were also the first team to provide mechanistic insights by which testosterone supplement may induce skeletal muscle fiber hypertrophy (Brown et al, J Endocrinol, 2009; Kovacheva et al., Endocrinology, 2010). This information is crucial for understanding the skeletal muscle pathophysiology in aging and for further research directed toward clinical management of successful aging, which could lay a foundation based on which rational hormone replacement therapy could be designed for delaying or preventing loss of muscle mass in elderly men as well as in other wasting states.

    3. Use of a Novel Antioxidant as a Part of Dietary supplement: The search for natural products that are culturally acceptable and understanding their mechanisms of action is a critical component in the fight to reduce health disparities and improve the overall health of the nation. Nonalcoholic fatty liver disease (NFLD) includes the whole spectrum of fatty liver, including steatosis, steatohepatitis, and cirrhosis. Oxidative stress is pivotal in the pathogenesis of NFLD. We examined the effects of a novel cystine based glutathione precursor fortified with selenium (FT061452 TM or F1) in preventing steatosis in ApoE-/- mice fed with high-fat diet. The results demonstrate that dietary supplementation of F1, a modified glutathione precursor prevents high fat diet-induced induced steatosis in ApoE-/- mice and emphasizes the suitability of this model for investigating the mechanisms of diet-induced steatosis.

    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Hasan KM, Friedman TC, Shao X, Parveen M, Sims C, Lee DL, Espinoza-Derout J, Sinha-Hikim I, Sinha-Hikim AP. E-cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases. Hepatology. 2019 06; 69(6):2442-2454. PMID: 30664268; PMCID: PMC6636679.
      Citations: 16     Fields:    Translation:HumansAnimals
    2. Hasan MK, Friedman TC, Sims C, Lee DL, Espinoza-Derout J, Ume A, Chalfant V, Lee ML, Sinha-Hikim I, Lutfy K, Liu Y, Mahata SK, Sinha-Hikim AP. a7-Nicotinic Acetylcholine Receptor Agonist Ameliorates Nicotine Plus High-Fat Diet-Induced Hepatic Steatosis in Male Mice by Inhibiting Oxidative Stress and Stimulating AMPK Signaling. Endocrinology. 2018 02 01; 159(2):931-944. PMID: 29272360; PMCID: PMC5776480.
      Citations: 12     Fields:    Translation:AnimalsCells
    3. Sinha-Hikim AP, Sinha-Hikim I, Friedman TC. Connection of Nicotine to Diet-Induced Obesity and Non-Alcoholic Fatty Liver Disease: Cellular and Mechanistic Insights. Front Endocrinol (Lausanne). 2017; 8:23. PMID: 28239368; PMCID: PMC5300964.
      Citations: 18     Fields:    
    4. Tsao J, Kovanecz I, Awadalla N, Gelfand R, Sinha-Hikim I, White RA, Gonzalez-Cadavid NF. Muscle Derived Stem Cells Stimulate Muscle Myofiber Repair and Counteract Fat Infiltration in a Diabetic Mouse Model of Critical Limb Ischemia. J Stem Cell Res Ther. 2016 Dec; 6(12). PMID: 28217409; PMCID: PMC5313052.
      Citations: 5     
    5. Sinha-Hikim I, Friedman TC, Falz M, Chalfant V, Hasan MK, Espinoza-Derout J, Lee DL, Sims C, Tran P, Mahata SK, Sinha-Hikim AP. Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell Tissue Res. 2017 04; 368(1):159-170. PMID: 27917437; PMCID: PMC5813800.
      Citations: 12     Fields:    Translation:AnimalsCells
    6. Sinha-Hikim I, Duran P, Shen R, Lee M, Friedman TC, Davidson MB. Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D. Horm Metab Res. 2015 Apr; 47(4):280-3. PMID: 25011019; PMCID: PMC4648252.
      Citations: 16     Fields:    Translation:Humans
    7. Sinha I, Sinha-Hikim AP, Wagers AJ, Sinha-Hikim I. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model. Cell Tissue Res. 2014 Sep; 357(3):815-21. PMID: 24859218; PMCID: PMC4149819.
      Citations: 21     Fields:    Translation:AnimalsCells
    8. Ivey R, Desai M, Green K, Sinha-Hikim I, Friedman TC, Sinha-Hikim AP. Additive effects of nicotine and high-fat diet on hepatocellular apoptosis in mice: involvement of caspase 2 and inducible nitric oxide synthase-mediated intrinsic pathway signaling. Horm Metab Res. 2014 Jul; 46(8):568-73. PMID: 24830635; PMCID: PMC4327908.
      Citations: 10     Fields:    Translation:AnimalsCells
    9. Sinha-Hikim I, Friedman TC, Shin CS, Lee D, Ivey R, Sinha-Hikim AP. Nicotine in combination with a high-fat diet causes intramyocellular mitochondrial abnormalities in male mice. Endocrinology. 2014 Mar; 155(3):865-72. PMID: 24424058; PMCID: PMC3929732.
      Citations: 16     Fields:    Translation:AnimalsCells
    10. Sinha-Hikim I, Sinha-Hikim AP, Parveen M, Shen R, Goswami R, Tran P, Crum A, Norris KC. Long-term supplementation with a cystine-based antioxidant delays loss of muscle mass in aging. J Gerontol A Biol Sci Med Sci. 2013 Jul; 68(7):749-59. PMID: 23459206; PMCID: PMC3674717.
      Citations: 23     Fields:    Translation:Animals
    11. Friedman TC, Sinha-Hikim I, Parveen M, Najjar SM, Liu Y, Mangubat M, Shin CS, Lyzlov A, Ivey R, Shaheen M, French SW, Sinha-Hikim AP. Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice. Endocrinology. 2012 Dec; 153(12):5809-20. PMID: 23093702; PMCID: PMC3512067.
      Citations: 28     Fields:    Translation:AnimalsCells
    12. Mangubat M, Lutfy K, Lee ML, Pulido L, Stout D, Davis R, Shin CS, Shahbazian M, Seasholtz S, Sinha-Hikim A, Sinha-Hikim I, O'Dell LE, Lyzlov A, Liu Y, Friedman TC. Effect of nicotine on body composition in mice. J Endocrinol. 2012 Mar; 212(3):317-26. PMID: 22138237; PMCID: PMC3444240.
      Citations: 29     Fields:    Translation:Animals
    13. Sinha-Hikim I, Shen R, Nzenwa I, Gelfand R, Mahata SK, Sinha-Hikim AP. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure. Apoptosis. 2011 Jun; 16(6):563-73. PMID: 21424555; PMCID: PMC4701037.
      Citations: 19     Fields:    Translation:HumansAnimalsCellsPHPublic Health
    14. Sinha-Hikim I, Sinha-Hikim AP, Shen R, Kim HJ, Kim H, French SW, Vaziri ND, Vaziri ND, Crum AC, Crum A, Rajavashisth TB, Norris KC. A novel cystine based antioxidant attenuates oxidative stress and hepatic steatosis in diet-induced obese mice. Exp Mol Pathol. 2011 Aug; 91(1):419-28. PMID: 21570964; PMCID: PMC3191382.
      Citations: 24     Fields:    Translation:AnimalsCells
    15. Sinha-Hikim I, Shen R, Paul Lee WN, Crum A, Vaziri ND, Norris KC. Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2010 Sep; 299(3):C638-42. PMID: 20592243; PMCID: PMC2944321.
      Citations: 13     Fields:    Translation:HumansCells
    16. Sinha-Hikim I, Shen R, Kovacheva E, Crum A, Vaziri ND, Norris KC. Inhibition of apoptotic signalling in spermine-treated vascular smooth muscle cells by a novel glutathione precursor. Cell Biol Int. 2010 Apr 01; 34(5):503-11. PMID: 20121705; PMCID: PMC3748361.
      Citations: 6     Fields:    Translation:HumansCells
    17. Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology. 2010 Feb; 151(2):628-38. PMID: 20022929; PMCID: PMC2817626.
      Citations: 69     Fields:    Translation:HumansAnimalsCells
    18. Brown D, Hikim AP, Kovacheva EL, Sinha-Hikim I. Mouse model of testosterone-induced muscle fiber hypertrophy: involvement of p38 mitogen-activated protein kinase-mediated Notch signaling. J Endocrinol. 2009 Apr; 201(1):129-39. PMID: 19144735; PMCID: PMC4732720.
      Citations: 19     Fields:    Translation:AnimalsCells
    19. Jia Y, Castellanos J, Wang C, Sinha-Hikim I, Lue Y, Swerdloff RS, Sinha-Hikim AP. Mitogen-activated protein kinase signaling in male germ cell apoptosis in the rat. Biol Reprod. 2009 Apr; 80(4):771-80. PMID: 19109224; PMCID: PMC2804830.
      Citations: 24     Fields:    Translation:AnimalsCells
    20. Braga M, Sinha Hikim AP, Datta S, Ferrini MG, Brown D, Kovacheva EL, Gonzalez-Cadavid NF, Sinha-Hikim I. Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice. Apoptosis. 2008 Jun; 13(6):822-32. PMID: 18461459; PMCID: PMC4732709.
      Citations: 59     Fields:    Translation:AnimalsCells
    21. Sinha-Hikim I, Braga M, Shen R, Sinha Hikim AP. Involvement of c-Jun NH2-terminal kinase and nitric oxide-mediated mitochondria-dependent intrinsic pathway signaling in cardiotoxin-induced muscle cell death: role of testosterone. Apoptosis. 2007 Nov; 12(11):1965-78. PMID: 17786558.
      Citations: 19     Fields:    Translation:HumansAnimalsCells
    22. Herbst KL, Calof OM, Hsia SH, Sinha-Hikim I, Woodhouse LJ, Buchanan TA, Bhasin S. Effects of transdermal testosterone administration on insulin sensitivity, fat mass and distribution, and markers of inflammation and thrombolysis in human immunodeficiency virus-infected women with mild to moderate weight loss. Fertil Steril. 2006 Jun; 85(6):1794-802. PMID: 16759927.
      Citations: 5     Fields:    Translation:Humans
    23. Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006 Aug; 91(8):3024-33. PMID: 16705073.
      Citations: 91     Fields:    Translation:HumansCells
    24. Singh AB, Lee ML, Sinha-Hikim I, Kushnir M, Meikle W, Rockwood A, Afework S, Bhasin S. Pharmacokinetics of a testosterone gel in healthy postmenopausal women. J Clin Endocrinol Metab. 2006 Jan; 91(1):136-44. PMID: 16263817.
      Citations: 10     Fields:    Translation:Humans
    25. Gray PB, Singh AB, Woodhouse LJ, Storer TW, Casaburi R, Dzekov J, Dzekov C, Sinha-Hikim I, Bhasin S. Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab. 2005 Jul; 90(7):3838-46. PMID: 15827094.
      Citations: 47     Fields:    Translation:HumansCTClinical Trials
    26. Choi HH, Gray PB, Storer TW, Calof OM, Woodhouse L, Singh AB, Padero C, Mac RP, Sinha-Hikim I, Shen R, Dzekov J, Dzekov C, Kushnir MM, Rockwood AL, Meikle AW, Lee ML, Hays RD, Bhasin S. Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab. 2005 Mar; 90(3):1531-41. PMID: 15613414.
      Citations: 24     Fields:    Translation:HumansCTClinical Trials
    27. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005 Feb; 90(2):678-88. PMID: 15562020.
      Citations: 147     Fields:    Translation:HumansCTClinical Trials
    28. 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. PMID: 15522925.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    29. Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab. 2004 Oct; 89(10):5245-55. PMID: 15472231.
      Citations: 86     Fields:    Translation:HumansCellsCTClinical Trials
    30. 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. PMID: 14684707.
      Citations: 55     Fields:    Translation:HumansCells
    31. Reisz-Porszasz S, Bhasin S, Artaza JN, Shen R, Sinha-Hikim I, Hogue A, Fielder TJ, Gonzalez-Cadavid NF. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab. 2003 Oct; 285(4):E876-88. PMID: 12824080.
      Citations: 109     Fields:    Translation:Animals
    32. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003 Jul; 285(1):E197-205. PMID: 12670837.
      Citations: 91     Fields:    Translation:HumansCellsCTClinical Trials
    33. Schroeder ET, Singh A, Bhasin S, Storer TW, Azen C, Davidson T, Martinez C, Sinha-Hikim I, Jaque SV, Terk M, Sattler FR. Effects of an oral androgen on muscle and metabolism in older, community-dwelling men. Am J Physiol Endocrinol Metab. 2003 Jan; 284(1):E120-8. PMID: 12388137.
      Citations: 16     Fields:    Translation:HumansCTClinical Trials
    34. Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R, Bhasin S. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002 Jul; 283(1):E154-64. PMID: 12067856.
      Citations: 101     Fields:    Translation:HumansCellsCTClinical Trials
    35. Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab. 2002 Jan; 87(1):136-43. PMID: 11788637.
      Citations: 44     Fields:    Translation:HumansCTClinical Trials
    36. Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF. Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging. 2002; 6(5):343-8. PMID: 12474026.
      Citations: 107     Fields:    
    37. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001 Dec; 281(6):E1172-81. PMID: 11701431.
      Citations: 205     Fields:    Translation:HumansCTClinical Trials
    38. Singh AB, Norris K, Modi N, Sinha-Hikim I, Shen R, Davidson T, Bhasin S. Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men. J Clin Endocrinol Metab. 2001 Jun; 86(6):2437-45. PMID: 11397836.
      Citations: 12     Fields:    Translation:Humans
    39. Javanbakht M, Singh AB, Mazer NA, Beall G, Sinha-Hikim I, Shen R, Bhasin S. Pharmacokinetics of a novel testosterone matrix transdermal system in healthy, premenopausal women and women infected with the human immunodeficiency virus. J Clin Endocrinol Metab. 2000 Jul; 85(7):2395-401. PMID: 10902784.
      Citations: 3     Fields:    Translation:HumansCTClinical Trials
    40. Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Phillips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA. 2000 Feb 09; 283(6):763-70. PMID: 10683055; PMCID: PMC3173037.
      Citations: 70     Fields:    Translation:HumansCTClinical Trials
    41. Zachwieja JJ, Smith SR, Sinha-Hikim I, Gonzalez-Cadavid N, Bhasin S. Plasma myostatin-immunoreactive protein is increased after prolonged bed rest with low-dose T3 administration. J Gravit Physiol. 1999 Oct; 6(2):11-5. PMID: 11543081.
      Citations: 17     Fields:    Translation:Humans
    42. Arver S, Sinha-Hikim I, Beall G, Guerrero M, Shen R, Bhasin S. Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. J Androl. 1999 Sep-Oct; 20(5):611-8. PMID: 10520573.
      Citations: 10     Fields:    Translation:HumansCTClinical Trials
    43. Salehian B, Jacobson D, Swerdloff RS, Grafe MR, Sinha-Hikim I, McCutchan JA. Testicular pathologic changes and the pituitary-testicular axis during human immunodeficiency virus infection. Endocr Pract. 1999 Jan-Feb; 5(1):1-9. PMID: 15251696.
      Citations: 2     Fields:    
    44. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci U S A. 1998 Dec 08; 95(25):14938-43. PMID: 9843994; PMCID: PMC24554.
      Citations: 143     Fields:    Translation:HumansAnimalsCells
    45. Bhasin S, Storer TW, Asbel-Sethi N, Kilbourne A, Hays R, Sinha-Hikim I, Shen R, Arver S, Beall G. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab. 1998 Sep; 83(9):3155-62. PMID: 9745419.
      Citations: 20     Fields:    Translation:HumansCTClinical Trials
    46. Sinha-Hikim I, Arver S, Beall G, Shen R, Guerrero M, Sattler F, Shikuma C, Nelson JC, Landgren BM, Mazer NA, Bhasin S. The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 1998 Apr; 83(4):1312-8. PMID: 9543161.
      Citations: 37     Fields:    Translation:HumansCells
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