 Aditi Bhargava, PhD
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| Title | Associate Professor in Residence |
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| School | UCSF School of Medicine |
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| Department | Surgery |
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| Address | 513 Parnassus Ave, Med Sci
San Francisco CA 94143
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| Phone | 415-502-8453 |
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 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.
Bibliographic
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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.
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Bhargava A, Clifton MS, 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 8; 110(2):731-6.
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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.
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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.
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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; 6(5):e19498.
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Bhargava A. CRF and urocortins: a challenging interaction between family members. Gastroenterology. 2011 May; 140(5):1391-4.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Pearce D, Bhargava A, Cole TJ. Aldosterone: its receptor, target genes, and actions. Vitam Horm. 2003; 66:29-76.
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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.
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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.
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Bell ME, Bhargava A, Soriano L, Laugero K, Akana SF, Dallman MF. Sucrose intake and corticosterone interact with cold to modulate ingestive behaviour, energy balance, autonomic outflow and neuroendocrine responses during chronic stress. J Neuroendocrinol. 2002 Apr; 14(4):330-42.
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Wang J, Barbry P, Maiyar AC, Rozansky DJ, Bhargava A, Leong M, Firestone GL, Pearce D. SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am J Physiol Renal Physiol. 2001 Feb; 280(2):F303-13.
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Bhargava A, Meijer OC, Dallman MF, Pearce D. Plasma membrane calcium pump isoform 1 gene expression is repressed by corticosterone and stress in rat hippocampus. J Neurosci. 2000 May 1; 20(9):3129-38.
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Pearce D, Verrey F, Chen SY, Mastroberardino L, Meijer OC, Wang J, Bhargava A. Role of SGK in mineralocorticoid-regulated sodium transport. Kidney Int. 2000 Apr; 57(4):1283-9.
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Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, Pearce D. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci U S A. 1999 Mar 2; 96(5):2514-9.
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