Aditi Bhargava, PhD

Recall Professor
Ob/Gyn, Reproductive Sciences
+1 415 476-3336

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.

Publications: 

Organ-Specific Glucose Uptake: Does Sex Matter?

Cells

Gandhi A, Tang R, Seo Y, Bhargava A

Chemical set enrichment analysis: Novel insights into sex-specific alterations in primary metabolites in posttraumatic stress and disturbed sleep.

Clinical and translational medicine

Bhargava A, Fan S, Lujan CR, Fiehn O, Neylan TC, Inslicht SS

Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue.

Scientific reports

Qu J, Fourman S, Fitzgerald M, Liu M, Nair S, Oses-Prieto J, Burlingame A, Morris JH, Davidson WS, Tso P, Bhargava A

Human Placenta Buffers the Fetus from Adverse Effects of Perceived Maternal Stress.

Cells

Vuppaladhadiam L, Lager J, Fiehn O, Weiss S, Chesney M, Hasdemir B, Bhargava A

Effects of stress-related peptides on chloride secretion in the mouse proximal colon.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

Liu S, Karo A, Agterberg S, Hua H, Bhargava A

Protective effects of urocortin 2 against caerulein-induced acute pancreatitis.

PloS one

Yuan J, Hasdemir B, Tan T, Chheda C, Rivier J, Pandol SJ, Bhargava A

Probing the Interactome of Corticotropin-Releasing Factor Receptor Heteromers Using Mass Spectrometry.

Methods in molecular biology (Clifton, N.J.)

Hasdemir B, Oses-Prieto JA, Burlingame A, Bhargava A

Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability.

The Journal of allergy and clinical immunology

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

Sexually dimorphic metabolic responses mediated by CRF2 receptor during nutritional stress in mice.

Biology of sex differences

Paruthiyil S, Hagiwara SI, Kundassery K, Bhargava A

Gastric corticotropin-releasing factor influences mast cell infiltration in a rat model of functional dyspepsia.

PloS one

Hagiwara SI, Kaushal E, Paruthiyil S, Pasricha PJ, Hasdemir B, Bhargava A

Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers.

Molecular biology of the cell

Hasdemir B, Mahajan S, Oses-Prieto J, Chand S, Woolley M, Burlingame A, Grammatopoulos DK, Bhargava A

Enriched environment and stress exposure influence splenic B lymphocyte composition.

PloS one

Gurfein BT, Hasdemir B, Milush JM, Touma C, Palme R, Nixon DF, Darcel N, Hecht FM, Bhargava A

One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.

JCI insight

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

Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation.

American journal of physiology. Regulatory, integrative and comparative physiology

Hasdemir B, Mhaske P, Paruthiyil S, Garnett EA, Heyman MB, Matloubian M, Bhargava A

Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.

The Journal of clinical investigation

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

Corticotropin-releasing factor receptor 2 mediates sex-specific cellular stress responses.

Molecular medicine (Cambridge, Mass.)

Kubat E, Mahajan S, Liao M, Ackerman L, Ohara PT, Grady EF, Bhargava A

Evidence for glutamate as a neuroglial transmitter within sensory ganglia.

PloS one

Kung LH, Gong K, Adedoyin M, Ng J, Bhargava A, Ohara PT, Jasmin L

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis.

Proceedings of the National Academy of Sciences of the United States of America

Bhargava A, Clifton MS, Mhaske P, Mhsake P, Liao M, Pothoulakis C, Leeman SE, Grady EF

Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival.

The Journal of cell biology

Kim HJ, Prasad V, Hyung SW, Lee ZH, Lee SW, Bhargava A, Pearce D, Lee Y, Kim HH

Urocortin 1 modulates immunosignaling in a rat model of colitis via corticotropin-releasing factor receptor 2.

American journal of physiology. Gastrointestinal and liver physiology

Chang J, Adams MR, Clifton MS, Liao M, Brooks JH, Hasdemir B, Bhargava A

Expression and role of serum and glucocorticoid-regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney.

American journal of physiology. Renal physiology

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

c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium.

American journal of physiology. Gastrointestinal and liver physiology

Samak G, Suzuki T, Bhargava A, Rao RK

Can satellite glial cells be therapeutic targets for pain control?

Neuron glia biology

Jasmin L, Vit JP, Bhargava A, Ohara PT

Local secretion of urocortin 1 promotes microvascular permeability during lipopolysaccharide-induced inflammation.

Endocrinology

Cureton EL, Ereso AQ, Victorino GP, Curran B, Poole DP, Liao M, Harken AH, Bhargava A

Gliopathic pain: when satellite glial cells go bad.

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

Ohara PT, Vit JP, Bhargava A, Romero M, Sundberg C, Charles AC, Jasmin L

Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo.

Journal of neurophysiology

Ohara PT, Vit JP, Bhargava A, 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.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Vit JP, Ohara PT, Bhargava A, Kelley K, Jasmin L

Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis.

Peptides

Chang J, Hoy JJ, Idumalla PS, Clifton MS, Pecoraro NC, Bhargava A

Role of calcitonin receptor-like receptor in colonic motility and inflammation.

American journal of physiology. Gastrointestinal and liver physiology

Clifton MS, Hoy JJ, Chang J, Idumalla PS, Fakhruddin H, Grady EF, Dada S, Corvera CU, Bhargava A

From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants.

Progress in neurobiology

Pecoraro N, Dallman MF, Warne JP, Ginsberg AB, Laugero KD, la Fleur SE, Houshyar H, Gomez F, Bhargava A, Akana SF

Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney.

American journal of physiology. Regulatory, integrative and comparative physiology

Ni XP, Bhargava A, Pearce D, Humphreys MH

Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum.

Proceedings of the National Academy of Sciences of the United States of America

la Fleur SE, Wick EC, Idumalla PS, Grady EF, Bhargava A

Regulation of epithelial ion transport by aldosterone through changes in gene expression.

Molecular and cellular endocrinology

Bhargava A, Wang J, Pearce D

Intermittent morphine administration induces dependence and is a chronic stressor in rats.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Houshyar H, Gomez F, Manalo S, Bhargava A, Dallman MF

Aldosterone: its receptor, target genes, and actions.

Vitamins and hormones

Pearce D, Bhargava A, Cole TJ

Glucocorticoids prolong Ca(2+) transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca(2+)-ATPase-1.

Molecular endocrinology (Baltimore, Md.)

Bhargava A, Mathias RS, McCormick JA, Dallman MF, Pearce D

Hypotonic induction of SGK1 and Na+ transport in A6 cells.

American journal of physiology. Renal physiology

Rozansky DJ, Wang J, Doan N, Purdy T, Faulk T, Bhargava A, Dawson K, Pearce D

The serum- and glucocorticoid-induced kinase is a physiological mediator of aldosterone action.

Endocrinology

Bhargava A, Fullerton MJ, Myles K, Purdy TM, Funder JW, Pearce D, Cole TJ

Monocrotaline induces interleukin-6 mRNA expression in rat lungs.

Heart disease (Hagerstown, Md.)

Bhargava A, Kumar A, Yuan N, Gewitz MH, Mathew R

Evaluation of a polymerase chain reaction for the diagnosis of tuberculosis.

Tubercle

Manjunath N, Shankar P, Rajan L, Bhargava A, Saluja S

Identification of Mycobacterium tuberculosis by polymerase chain reaction.

Lancet (London, England)

Shankar P, Manjunath N, Lakshmi R, Aditi B, Seth P