Aditi Bhargava, PhD

Title(s)Professor, Ob/Gyn, Reproductive Sciences
SchoolSchool of Medicine
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    Collapse Biography 
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    University of California, San FranciscoPostdoctoral StudiesGraduate Division

    Collapse Overview 
    Collapse Overview
    The incidence of stress-related illnesses like irritable bowel syndrome and inflammatory bowel disease (IBD), have surged in the past few decades. The underlying cause of these and other stress-related diseases involves a complex interaction between genes and environment. In response to a stressor, a plethora of genes are rapidly turned "on" (activated) or "off" (repressed).

    Some of these genes and their functions are known, but others remain unidentified. The long-term goal of our laboratory is to understand where these genes fit in response to a stressor and the interactions between the gut and brain in stress-related disorders. Recently, we have focused on delineating how glucocorticoids, which are released in response to a stressor, regulate gene function, and on linking molecular regulation to its physiological function.

    Our recent interests focus on the regulation and function of the corticotropin-releasing factor (CRF) family of neuropeptides and their receptors, because their expression levels correlate with the degree of gastrointestinal inflammation in patients with IBD. Our hypothesis is that final inhibitory or stimulatory outcomes of gastrointestinal inflammation and motility functions depend on the differing spatial distribution (within the gastrointestinal tract) and temporal expression levels of these ligands and their receptor.

    We have found that perturbations in the CRF-R2 receptor system render the mice more susceptible to sudden stress and immune challenges. We hope our research will establish how these neuropeptides help maintain a normal immune response in the gut and whether manipulation of CRF/urocortins can help ameliorate intestinal inflammation. Therapies that target this inflammatory pathway could improve the quality of life for patients with inflammatory bowel diseases and decrease the lifetime cost of treatment.

    Collapse Research 
    Collapse Research Activities and Funding
    Neuroplasticity of the gut-brain axis in functional dyspepsia
    NIH/NIDDK R01DK097518May 1, 2014 - Apr 30, 2017
    Role: Principal Investigator
    Regulation and Function of Urocortins and their Receptors
    NIH/NIDDK R01DK080787Apr 1, 2009 - Mar 31, 2014
    Role: Principal Investigator
    Regulation and Function of Urocortins and their Receptor
    NIH/NIDDK R56DK080787Apr 1, 2008 - Aug 31, 2016
    Role: Principal Investigator
    Site-specific Gene Silencing by RNA Interference
    NIH/NIMH R21MH070650Mar 22, 2004 - Feb 28, 2007
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Hagiwara SI, Hasdemir B, Heyman MB, Chang L, Bhargava A. Plasma Corticotropin-Releasing Factor Receptors and B7-2? Extracellular Vesicles in Blood Correlate with Irritable Bowel Syndrome Disease Severity. Cells. 2019 Jan 30; 8(2). PMID: 30704133.
      View in: PubMed
    2. D'Costa S, Ayyadurai S, Gibson AJ, Mackey E, Rajput M, Sommerville LJ, Wilson N, Li Y, Kubat E, Kumar A, Subramanian H, Bhargava A, Moeser AJ. Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability. J Allergy Clin Immunol. 2018 Nov 12. PMID: 30439403.
      View in: PubMed
    3. Paruthiyil S, Hagiwara SI, Kundassery K, Bhargava A. Sexually dimorphic metabolic responses mediated by CRF2 receptor during nutritional stress in mice. Biol Sex Differ. 2018 11 06; 9(1):49. PMID: 30400826.
      View in: PubMed
    4. Hagiwara SI, Kaushal E, Paruthiyil S, Pasricha PJ, Hasdemir B, Bhargava A. Gastric corticotropin-releasing factor influences mast cell infiltration in a rat model of functional dyspepsia. PLoS One. 2018; 13(9):e0203704. PMID: 30192883.
      View in: PubMed
    5. Strumwasser A, Bhargava A, Victorino GP. Attenuation of endothelial phosphatidylserine exposure decreases ischemia-reperfusion induced changes in microvascular permeability. J Trauma Acute Care Surg. 2018 Jun; 84(6):838-846. PMID: 29538229.
      View in: PubMed
    6. Hasdemir B, Mahajan S, Oses-Prieto J, Chand S, Woolley M, Burlingame A, Grammatopoulos DK, Bhargava A. Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers. Mol Biol Cell. 2017 Sep 01; 28(18):2386-2399. PMID: 28701349.
      View in: PubMed
    7. Gurfein BT, Hasdemir B, Milush JM, Touma C, Palme R, Nixon DF, Darcel N, Hecht FM, Bhargava A. Enriched environment and stress exposure influence splenic B lymphocyte composition. PLoS One. 2017; 12(7):e0180771. PMID: 28704473.
      View in: PubMed
    8. Gao MH, Giamouridis D, Lai NC, Walenta E, Paschoal VA, Kim YC, Miyanohara A, Guo T, Liao M, Liu L, Tan Z, Ciaraldi TP, Schenk S, Bhargava A, Oh DY, Hammond HK. One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance. JCI Insight. 2016 09 22; 1(15):e88322. PMID: 27699250.
      View in: PubMed
    9. Hasdemir B, Mhaske P, Paruthiyil S, Garnett EA, Heyman MB, Matloubian M, Bhargava A. Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation. Am J Physiol Regul Integr Comp Physiol. 2016 06 01; 310(11):R1244-57. PMID: 27053649; PMCID: PMC4935495 [Available on 06/01/17].
    10. Gong K, Bhargava A, Jasmin L. GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats: implication for opiate-induced hyperalgesia. Pain. 2016 Jan; 157(1):147-58. PMID: 26335908; PMCID: PMC4957526 [Available on 01/01/17].
    11. Kido-Nakahara M, Buddenkotte J, Kempkes C, Ikoma A, Cevikbas F, Akiyama T, Nunes F, Seeliger S, Hasdemir B, Mess C, Buhl T, Sulk M, Müller FU, Metze D, Bunnett NW, Bhargava A, Carstens E, Furue M, Steinhoff M. Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus. J Clin Invest. 2014 Jun; 124(6):2683-95. PMID: 24812665; PMCID: PMC4038561.
    12. Gong K, Kung LH, Magni G, Bhargava A, Jasmin L. Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury. PLoS One. 2014; 9(4):e95491. PMID: 24748330; PMCID: PMC3991716.
    13. Mahajan S, Liao M, Barkan P, Takahashi K, Bhargava A. Urocortin 3 expression at baseline and during inflammation in the colon: corticotropin releasing factor receptors cross-talk. Peptides. 2014 Apr; 54:58-66. PMID: 24462512; PMCID: PMC4006935.
    14. Kubat E, Mahajan S, Liao M, Ackerman L, Ohara PT, Grady EF, Bhargava A. Corticotropin-releasing factor receptor 2 mediates sex-specific cellular stress responses. Mol Med. 2013 Jul 24; 19:212-22. PMID: 23835907.
      View in: PubMed
    15. Kung LH, Gong K, Adedoyin M, Ng J, Bhargava A, Ohara PT, Jasmin L. Evidence for glutamate as a neuroglial transmitter within sensory ganglia. PLoS One. 2013; 8(7):e68312. PMID: 23844184; PMCID: PMC3699553.
    16. Bhargava A, Clifton MS, Mhaske P, Mhsake P, Liao M, Pothoulakis C, Leeman SE, Grady EF. Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis. Proc Natl Acad Sci U S A. 2013 Jan 08; 110(2):731-6. PMID: 23267070; PMCID: PMC3545755.
    17. Kim HJ, Prasad V, Hyung SW, Lee ZH, Lee SW, Bhargava A, Pearce D, Lee Y, Kim HH. Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival. J Cell Biol. 2012 Dec 24; 199(7):1145-58. PMID: 23266958; PMCID: PMC3529522.
    18. Cottrell GS, Alemi F, Kirkland JG, Grady EF, Corvera CU, Bhargava A. Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract. Peptides. 2012 Jun; 35(2):202-11. PMID: 22484227; PMCID: PMC3356482.
    19. Hasdemir B, Mahajan S, Bunnett NW, Liao M, Bhargava A. Endothelin-converting enzyme-1 actions determine differential trafficking and signaling of corticotropin-releasing factor receptor 1 at high agonist concentrations. Mol Endocrinol. 2012 Apr; 26(4):681-95. PMID: 22322595; PMCID: PMC3327357.
    20. Liu L, Li Q, Sapolsky R, Liao M, Mehta K, Bhargava A, Pasricha PJ. Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults. PLoS One. 2011 May 12; 6(5):e19498. PMID: 21589865; PMCID: PMC3093391.
    21. Bhargava A. CRF and urocortins: a challenging interaction between family members. Gastroenterology. 2011 May; 140(5):1391-4. PMID: 21447312.
      View in: PubMed
    22. Chang J, Adams MR, Clifton MS, Liao M, Brooks JH, Hasdemir B, Bhargava A. Urocortin 1 modulates immunosignaling in a rat model of colitis via corticotropin-releasing factor receptor 2. Am J Physiol Gastrointest Liver Physiol. 2011 May; 300(5):G884-94. PMID: 21330446; PMCID: PMC3094137.
    23. Aggarwal S, Suzuki T, Taylor WL, Bhargava A, Rao RK. Contrasting effects of ERK on tight junction integrity in differentiated and under-differentiated Caco-2 cell monolayers. Biochem J. 2011 Jan 01; 433(1):51-63. PMID: 20961289; PMCID: PMC4438673.
    24. Pao AC, Bhargava A, Di Sole F, Quigley R, Shao X, Wang J, Thomas S, Zhang J, Shi M, Funder JW, Moe OW, Pearce D. Expression and role of serum and glucocorticoid-regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney. Am J Physiol Renal Physiol. 2010 Dec; 299(6):F1496-506. PMID: 20926631; PMCID: PMC3006302.
    25. Samak G, Suzuki T, Bhargava A, Rao RK. c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2010 Sep; 299(3):G572-84. PMID: 20595622.
      View in: PubMed
    26. Jasmin L, Vit JP, Bhargava A, Ohara PT. Can satellite glial cells be therapeutic targets for pain control? Neuron Glia Biol. 2010 Feb; 6(1):63-71. PMID: 20566001; PMCID: PMC3139431.
    27. Cureton EL, Ereso AQ, Victorino GP, Curran B, Poole DP, Liao M, Harken AH, Bhargava A. Local secretion of urocortin 1 promotes microvascular permeability during lipopolysaccharide-induced inflammation. Endocrinology. 2009 Dec; 150(12):5428-37. PMID: 19819946; PMCID: PMC2795720.
    28. Ohara PT, Vit JP, Bhargava A, Romero M, Sundberg C, Charles AC, Jasmin L. Gliopathic pain: when satellite glial cells go bad. Neuroscientist. 2009 Oct; 15(5):450-63. PMID: 19826169; PMCID: PMC2852320.
    29. Ohara PT, Vit JP, Bhargava A, Jasmin L. Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo. J Neurophysiol. 2008 Dec; 100(6):3064-73. PMID: 18715894; PMCID: PMC2604845.
    30. Gavrila AM, Robinson B, Hoy J, Stewart J, Bhargava A, Amir S. Double-stranded RNA-mediated suppression of Period2 expression in the suprachiasmatic nucleus disrupts circadian locomotor activity in rats. Neuroscience. 2008 Jun 23; 154(2):409-14. PMID: 18511208.
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    31. Vit JP, Ohara PT, Bhargava A, Kelley K, Jasmin L. Silencing the Kir4.1 potassium channel subunit in satellite glial cells of the rat trigeminal ganglion results in pain-like behavior in the absence of nerve injury. J Neurosci. 2008 Apr 16; 28(16):4161-71. PMID: 18417695; PMCID: PMC2533133.
    32. Chang J, Hoy JJ, Idumalla PS, Clifton MS, Pecoraro NC, Bhargava A. Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis. Peptides. 2007 Jul; 28(7):1453-60. PMID: 17586086; PMCID: PMC3718314.
    33. Clifton MS, Hoy JJ, Chang J, Idumalla PS, Fakhruddin H, Grady EF, Dada S, Corvera CU, Bhargava A. Role of calcitonin receptor-like receptor in colonic motility and inflammation. Am J Physiol Gastrointest Liver Physiol. 2007 Jul; 293(1):G36-44. PMID: 17363466.
      View in: PubMed
    34. Vit JP, Jasmin L, Bhargava A, Ohara PT. Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain. Neuron Glia Biol. 2006 Nov; 2(4):247-57. PMID: 18568096; PMCID: PMC2435170.
    35. Pecoraro N, Dallman MF, Warne JP, Ginsberg AB, Laugero KD, la Fleur SE, Houshyar H, Gomez F, Bhargava A, Akana SF. From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants. Prog Neurobiol. 2006 Aug; 79(5-6):247-340. PMID: 16982128.
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    36. Warne JP, Horneman HF, Wick EC, Bhargava A, Pecoraro NC, Ginsberg AB, Akana SF, Dallman MF. Comparison of superior mesenteric versus jugular venous infusions of insulin in streptozotocin-diabetic rats on the choice of caloric intake, body weight, and fat stores. Endocrinology. 2006 Nov; 147(11):5443-51. PMID: 16873535.
      View in: PubMed
    37. Ni XP, Bhargava A, Pearce D, Humphreys MH. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Am J Physiol Regul Integr Comp Physiol. 2006 Mar; 290(3):R560-7. PMID: 16195498.
      View in: PubMed
    38. la Fleur SE, Wick EC, Idumalla PS, Grady EF, Bhargava A. Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum. Proc Natl Acad Sci U S A. 2005 May 24; 102(21):7647-52. PMID: 15883387; PMCID: PMC1140406.
    39. Bhargava A, Dallman MF, Pearce D, Choi S. Long double-stranded RNA-mediated RNA interference as a tool to achieve site-specific silencing of hypothalamic neuropeptides. Brain Res Brain Res Protoc. 2004 Jun; 13(2):115-25. PMID: 15171994.
      View in: PubMed
    40. Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF. Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology. 2004 Aug; 145(8):3754-62. PMID: 15142987.
      View in: PubMed
    41. Bhargava A, Pearce D. Mechanisms of mineralocorticoid action: determinants of receptor specificity and actions of regulated gene products. Trends Endocrinol Metab. 2004 May-Jun; 15(4):147-53. PMID: 15109612.
      View in: PubMed
    42. Bhargava A, Wang J, Pearce D. Regulation of epithelial ion transport by aldosterone through changes in gene expression. Mol Cell Endocrinol. 2004 Mar 31; 217(1-2):189-96. PMID: 15134817.
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    43. Houshyar H, Gomez F, Manalo S, Bhargava A, Dallman MF. Intermittent morphine administration induces dependence and is a chronic stressor in rats. Neuropsychopharmacology. 2003 Nov; 28(11):1960-72. PMID: 12915862.
      View in: PubMed
    44. Adams M, Meijer OC, Wang J, Bhargava A, Pearce D. Homodimerization of the glucocorticoid receptor is not essential for response element binding: activation of the phenylethanolamine N-methyltransferase gene by dimerization-defective mutants. Mol Endocrinol. 2003 Dec; 17(12):2583-92. PMID: 12933902.
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    45. Pearce D, Bhargava A, Cole TJ. Aldosterone: its receptor, target genes, and actions. Vitam Horm. 2003; 66:29-76. PMID: 12852252.
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    46. Bhargava A, Mathias RS, McCormick JA, Dallman MF, Pearce D. Glucocorticoids prolong Ca(2+) transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca(2+)-ATPase-1. Mol Endocrinol. 2002 Jul; 16(7):1629-37. PMID: 12089356.
      View in: PubMed
    47. Rozansky DJ, Wang J, Doan N, Purdy T, Faulk T, Bhargava A, Dawson K, Pearce D. Hypotonic induction of SGK1 and Na+ transport in A6 cells. Am J Physiol Renal Physiol. 2002 Jul; 283(1):F105-13. PMID: 12060592.
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    48. Bhargava A, Fullerton MJ, Myles K, Purdy TM, Funder JW, Pearce D, Cole TJ. The serum- and glucocorticoid-induced kinase is a physiological mediator of aldosterone action. Endocrinology. 2001 Apr; 142(4):1587-94. PMID: 11250940.
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    49. Bhargava A, Kumar A, Yuan N, Gewitz MH, Mathew R. Monocrotaline induces interleukin-6 mRNA expression in rat lungs. Heart Dis. 1999 Jul-Aug; 1(3):126-32. PMID: 11720614.
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    50. Manjunath N, Shankar P, Rajan L, Bhargava A, Saluja S. Evaluation of a polymerase chain reaction for the diagnosis of tuberculosis. Tubercle. 1991 Mar; 72(1):21-7. PMID: 1882442.
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    51. Shankar P, Manjunath N, Lakshmi R, Aditi B, Seth P. Identification of Mycobacterium tuberculosis by polymerase chain reaction. Lancet. 1990 Feb 17; 335(8686):423. PMID: 1968160.
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