Sanjay Jain, MD, PhD

Associate Professor of Medicine, Division of Nephrology

Additional Titles

Mailing Address

Division of Nephrology

  • Mailing Address: 660 S. Euclid Ave., CB 8126
    St. Louis, MO 63110

Education

  • AB, Genetics: University of California-Berkeley, Berkeley, CA (1990)
  • MD: Northwestern University, Chicago, IL (1999)
  • PhD, Integrated Biology: Northwestern University, Chicago, IL (1999)
  • Residency, Anatomic Pathology: Washington University School of Medicine, St. Louis, MO (2001)
  • Postdoctoral Fellow, Cancer, Neurodevelopment: Washington University School of Medicine, St. Louis, MO (2004)

Recognition

2018-2020
Steering Committee, Human Biomolecular Atlas Project (HuBMAP) (NIH – common fund)

2017-Present
Executive Committee, Kidney Precision Medicine Project (KPMP, NIH/NIDDK)
– Chair, Quality control Tissue Interrogation Sites (KPMP)
– Co-Chair, Pathology and Molecular Integration Committee (KPMP)

2017-2019
Chair, NIDDK/KMBD study section, Center for Scientific Review, NIH

2017-2019
Steering Committee, Kidney Precision Medicine Project (NIH/NIDDK)

2017-2018
American Society of Nephrology, Program Committee

2017
First Prize, British Medical Association book award in the Pathology category for Diagnostic Pathology: Kidney Diseases, 2nd edition, Editor Robert Colvin and Anthony Chang, Publisher- Elsevier Inc. 2015. ISBN 978-0-323-37707-2; contributed 9 chapters

2016-present
Steering Committee, ReBuilding a Kidney (RBK) project (NIH/NIDDK)

2014-2019
Standing member, KMBD study section, Center for Scientific Review, NIH

2014
Study Section Member, Center for Scientific Review, KMBD, NIH

2013-2016
Steering and Executive Committee, Genitourinary Development Molecular Anatomy Project (GUDMAP) (NIDDK)

2013
ASCI Inductee, American Society of Clinical Investigators
Steering and Executive Committee, GUDMAP, NIH-NIDDK

2012
Editorial Board Member, Journal of Biological Chemistry

2009
CDI Investigator Award, Children’s Discovery Institute

2008-2010
Board of Directors, Chair Communications and Website Committee, Renal Pathology Society

2008
Board of Directors, Chair, communications and publications committee, Renal Pathology Society

2007
Pirani Award, Renal Pathology Society
KUFA-RPS research award, Kidney and Urology Foundation

2004
K08 Award, NIH-NICHD

2003
NIH-LRP award (3 competitive renewals), NIH

2001
NRSA training grant fellowship (T32), Washington University School of Medicine, St. Louis

1995
Graduate Student Fellowship Award, International Society of Toxicology

1995
Molecular Biology Specialty Section Award, First Prize, International Society of Toxicology

1991
MSTP Fellowship, Northwestern University

1990
Graduation with Distinction in General Scholarship
High Honors for Undergraduate Thesis
Departmental Citation for Outstanding Accomplishment in Genetics, University of California, Berkeley, CA

1984
Open Merit Scholarship, Indian Ministry of Education, India

Research Interests

Research Interests:  Kidney development, ureter development, CAKUT, AKI, genomics, neurodevelopment, GDNF, RET, branching morphogenesis, genetics, biobanking, translational research, biomarkers, regeneration, stem cells, bladder regeneration, bladder pain

Funding: NIH/NIDDK, March of Dimes, GUDMAP consortium, BJIH

Research Description
The major goal of my laboratory is to decipher molecular and genetic mechanisms underlying development and diseases of the kidneys and lower urinary tract. Our main hypothesis is that developmentally important genes play a role in congenital malformations, repair and regeneration of organs in acute and chronic diseases, and cancer. To this end we use disease model systems and “omic” technologies and integrate basic science and clinical research. Below are the major ongoing projects.

Investigations of early urogenital development and patterning. Glial cell line-derived neurotrophic factor (GDNF)-RET receptor tyrosine kinase signaling is required for kidney formation (ureteric bud induction), ureter maturation and branching morphogenesis. These events rely on reciprocal interactions between the RET expressing ureteric bud epithelial cells that are also the precursors for the collecting ducts, and the GDNF expressing metanephric mesenchyme. We are using GDNF-RET signaling system as a paradigm to decipher the cellular events (proliferation, cell movements, cell death and cell interactions) and mechanisms during early development of the Wolffian duct, ureteric budding and branching, insertion of ureter into the cloaca and innervation of the urinary tract. Ongoing studies include using novel genetically engineered mice, whole mount 4-D live time-lapse microscopy, population and single cells analysis of defined cell-types to determine the fate of RET-expressing cells in the genitourinary tract, role of RET associated pathways in acute injury and regeneration, and genetic abnormalities in CAKUT patients. These studies will provide insights into pathogenesis, diagnosis and treatment of CAKUT and fundamental knowledge to make new kidneys and ureters.

Discovery of genetic variants associated with kidney disease and their mechanisms of action. In collaboration with pathologists, pediatric nephrologists and urologists we have enrolled several hundred patients from the Midwest region with a spectrum of kidney diseases and collected their serum, plasma, cells, urine and DNA. The goal is to use these resources to discover new biomarkers associated with diagnoses and prognosis, and gene variants associated with disease. Our major focus is currently on CAKUT and glomerular diseases using whole exome or custom targeted exome sequencing and then using model systems in vitro and in vivo to understand causative mechanisms. These studies will identify new causes of CAKUT, and provide novel insights into how developmentally important genes cause these defects, lead to CKD and renal failure.

Mechanisms of acute injury and regeneration. We have implemented various models of acute injury to the kidneys (rhabdomyolysis, ischemia-reperfusion injury, ureteral obstruction) and to the bladder (UTI, chemical toxicity). We are using these in different scenarios to determine how interactions between development genes and environment impact repair, regeneration and function. In the lower urinary tract we are particularly interested in interactions between the peripheral nervous system and epithelial homoeostasis.

Publications

Selected Publications

Sanjay Jain and Feng Chen. Molecular Pathology of Congenital Renal Malformations Clinical Kidney Journal. 2018. In press.

Hongtao Zhang, Mazdak Bagherie-Lachidan, Caroline Badouel, Leonie Enderle, Philippos Peidis, Rod Bremner, Sanjay Jain, Helen McNeill. FAT4 fine-tunes kidney development by regulating RET signaling. Dev Cell, 2018. In press.

Lai Kuan Dionne, Kyuhwan Shim, Masato Hoshi, Tao Cheng, Jinzhi Wang, Veronique Marthiens, Amanda Knoten, Renata Basto, Sanjay Jain, and Moe R. Mahjoub. Centrosome Amplification Disrupts Renal Development and Causes Cystic Dysplasia. Journal of Cell Biology, 2018. In press.

Hoshi M, Reginensi A, Joens M, Fitzpatrick J, McNeill H, Jain S. Distinct RET and YAP signals regulate the fusion of Wolffian duct and cloaca through a novel reciprocal spatiotemporally controlled apoptosis. JASN, 2018. 29(3):775-783. PMID: 29326158. PMCID: PMC5827592.

Wilfert, A. B., K. R. Chao, M. Kaushal, S. Jain, S. Zollner, D. R. Adams and D. F. Conrad. Genome-wide significance testing of variation from single case exomes. Nat. Genet. 2016; 48(12):1455-1461 10.1038/ng.3697. PMID: 27618218; PMCID: PMC5097006

Emily Ma, Joel Vetter, Laura Bliss, H. Henry Lai, Indira U. Mysorekar, Sanjay Jain. A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder. Am J Physiol Gastrointest Renal Physiol. 2016: Jul 1;311(1):F28-34 PMID: 27029431. PMCID: PMC4967156

Reginensi A, Hoshi M, Boualia SK, Bouchard M, Jain S, McNeill H. Yap and Taz are Required for Ret-Dependent Urinary Tract Morphogenesis. Development, 2015. 142(15):2696-2703. PMID: 26243870. PMCID: PMC4529030

Anyaegbu E, Shaw A, Hruska K, and Jain S. Clinical Phenotype of APOL-1 Nephropathy in Young Relatives of Patients with End Stage Renal Disease. Pediatric Nephrology, 2014 Dec 23. [Epub ahead of print] PMID: 25530085

Sanjay Jain, MD, PhD, Michiel J. Noordam, PhD, Masato Hoshi, MD, PhD, Francesco L. Vallania, PhD, Donald F. Conrad, PhD. Validating single cell genomics for the study of renal development. Kidney International, 2014Apr 23. doi: 10.1038/ki.2014.104. [Epub ahead of print] PMID: 24759149. PMCID: PMC4207726

Joseph P Gaut, Dan L Crimmins, Matt F Ohlendorf, Christina M Lockwood, Terry A Griest, Nancy A Brada, Masato Hoshi, Bryan Sato, Richard S Hotchkiss, Sanjay Jain, and Jack H Ladenson. Development of an Immunoassay for the Kidney Specific Protein myo-Inositol Oxygenase, a Potential Biomarker of Acute Kidney Injury. Clinical Chemistry, 2014 May;60(5):747-57.PMID: 24486646

Golden, J. P., DeMaro III, J.A , Knoten, A., Hoshi, M., Pehek, E., Johnson, Jr., E.M. Gereau IV,R.W., Jain, S. (2013) Dopamine-dependent compensation maintains motor behavior in mice with developmental ablation of dopaminergic neurons Journal of Neuroscience. 2013 Oct 23;33(43):17095-107.PMID: 24155314

Rajshekhar Chatterjee, Mary Hoffman, Paul Cliften, Surya Seshan, Helen Liapis, Sanjay Jain. Targeted candidate exome capture in conjunction with multiindexing and next-generation sequencing identifies known and novel deleterious variants in Alport’s and renal malformations. PloS One, 2013. 8(10):e76369. PMID: 24130771

Davis TK, Hoshi M, and Jain S. Stage specific requirement of Gfrα1 in the ureteric epithelium during kidney development. Mech Dev. 2013 Mar 28. doi:pii: S0925-4773(13)00025-7. 10.1016/j.mod.2013.03.001. [Epub ahead of print] PMID:23542432. “PMCID-In Process” NIHMS 462467.

Chatterjee R, Ramos E, Hmiel P, Beck A, Hruska K, Coplen D, Liapis H, Mitra R, Austin P, Druley T and Jain S. Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET signaling complex in a cohort of living US patients with urinary tract malformations. ­Human Genetics2012: Nov;131(11):1725-38. PMID: 22729463. PMCID: PMC3551468.

Hoshi M, Batourina E, Mendelsohn, C and Jain S. Novel regulatory mechanisms of early upper and lower urinary tract patterning by RetY1015 docking tyrosine in mice. Development2012: Jul;139(13):2405-15. PMID: 22627285. PMCID: PMC3367447. Featured in Research Highlights by Susan J. Allison- Nature Reviews Nephrology 8, 432 (August 2012).

Jain S, De Petris L, Hoshi M, Akilesh S, Chatterjee R and Liapis H. Expression profiles of podocytes exposed to high glucose reveal new insights into early diabetic glomerulopathy. Lab. Invest. 2011: 91:488-498. (cover illustration). PMID:21102505. PMCID: PMC3068212. PMCID:PMC3367447

Jain S, Knoten A, Hoshi M, Wang H, Vohra B, Heuckeroth R and Milbrandt J. Organotypic specificity of RET-docking tyrosine residues in pathogenesis of neurocristopathies and renal malformations in mice. J Clin Invest 2010: 120(3): 778-90.(featured in highlights of the month). PMID:20160347. PMCID: PMC2827965

Golden J, Hoshi M, Nassar M, Enomoto H, Wood J, Milbrandt J, Gereau R, Johnson EMJr, and Jain S. RET Signaling is Required for Survival and Normal Function of Non-Peptidergic Nociceptors. J. Neurosci2010: 30(11):3983-94. PMID: 20237269. PMCID: PMC2850282