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Principal Investigator: Juan Pablo Arroyo Ornelas
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $158,436
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Chronic Kidney Disease (CKD) affects 15% of the US adult population 30 and vasopressin is
associated with progression of non-diabetic, diabetic, and polycystic kidney disease (PKD). 1-18
However, the specific mechanism(s) through which vasopressin worsens progression of kidney
disease are unclear. Vasopressin is the biologically active end-product of a 164 amino acid pre-
pro-peptide and physiologic production is currently thought to be limited to the brain. We
recently found that vasopressin is also made in the kidney under physiologic conditions and
expression is increased in PKD in both humans and mice. Therefore, the aim of this project is to
understand the function, regulation, and impact of kidney-derived vasopressin in health and
disease. We have preliminary data that show that mice that lack kidney-derived vasopressin in
the distal nephron have altered water balance. We propose to (1) determine the mechanism
through which kidney-derived vasopressin influences water balance and (2) determine if kidney-
derived vasopressin is involved cyst growth and progression of PKD. Successful completion of
this project will help clarify the mechanism(s) through which the interplay between local and
systemic vasopressin signaling impacts kidney disease, potentially identifying new therapeutic
targets and approaches for CKD and PKD. Work will occur in one of the largest and most
scientifically diverse nephrology divisions in the world, within the Vanderbilt University Medical
Center Department of Medicine. This project has already received extensive external (Harold
Amos Medical Faculty Development Award – 2020) and institutional support in the form of
financial support and a comprehensive career development plan involving internal and external
mentorship, workshops, and coursework.
Terms: <21+ years old><AQP-CD><AQP2 protein><Academic Medical Centers><Adult><Adult Human><Affect><Amino Acids><Antibodies><Antidiuretic Hormone><Aquaporins><Award><Binding><Blood Plasma><Blood Pressure><Body Weight decreased><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Growth in Number><Cell Multiplication><Cell Polarity><Cell Proliferation><Cell Signaling><Cells><Cellular Proliferation><Chronic Kidney Failure><Chronic Renal Disease><Chronic Renal Failure><Common Rat Strains><Cyst><Cyst Fluid><Data><Development><Development Plans><Diabetic Kidney Disease><Diabetic Nephropathy><Disease><Disorder><Distal><Duct><Duct (organ) structure><Ductal Cell><Ductal Epithelial Cell><Dysfunction><Educational workshop><Encephalon><Endocrine Gland Secretion><Epithelial Cell Proliferation><Equilibrium><Extracellular Fluid><Faculty Education><Faculty Training><Financial Support><Fluids and Secretions><Functional disorder><G Protein-Complex Receptor><G Protein-Coupled Receptor Genes><G-Protein-Coupled Receptors><GPCR><Generalized Growth><Growth><Health><Hormones><Human><Hydrogen Oxide><Hypotension><Hypothalamic structure><Hypothalamus><In Vitro><Institution><Intracellular Communication and Signaling><Investigators><KO mice><Kidney><Kidney Diseases><Kidney Urinary System><Knock-out Mice><Knockout Mice><Low Blood Pressure><Measures><Mediating><Medical Faculty><Medicine><Mentorship><Mice><Mice Mammals><Mitogenesis><Modeling><Modern Man><Molecular Interaction><Murine><Mus><Nephrology><Nephrons><Nephropathy><Null Mouse><Patients><Phosphorylation><Physiologic><Physiological><Physiology><Physiopathology><Plasma><Plasma Serum><Play><Polycystic Kidney><Polycystic Kidney Diseases><Population><Positive Control of Cell Proliferation><Production><Proliferating><Protein Phosphorylation><Rat><Rats Mammals><Rattus><Receptor Activation><Receptor Signaling><Regulation><Renal Disease><Renal function><Reproducibility><Research Personnel><Researchers><Reticuloendothelial System, Serum, Plasma><Role><Signal Transduction><Signal Transduction Systems><Signaling><Stimulation of Cell Proliferation><Stimulus><Stress><Teacher Education><Teacher Educator><Teacher Preparation><Teacher Professional Development><Teacher Training><Testing><Therapeutic Hormone><Tissue Growth><Transgenic Mice><University Medical Centers><Uriniferous Tube><V2 Receptors><Vascular Hypotensive Disorder><Vasopressins><WCH-CD><Water><Water Channel Proteins><Weight Loss><Weight Reduction><Work><Workshop><absorption><adulthood><aminoacid><aquaporin-2><aquaporin-CD><balance><balance function><beta-Hypophamine><biological signal transduction><body weight loss><career development><cellular polarity><chronic kidney disease><collecting duct water channel><developmental><faculty development><faculty professional development><financial assistance><hypothalamic><instructor training><kidney disorder><kidney epithelial cell><kidney function><mortality><mouse model><murine model><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><non-diabetic><nondiabetic><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><ontogeny><pathophysiology><prevent><preventing><pro-pressophysin><pro-vasopressin><propressophysin><renal><renal disorder><social role><teacher development><water channel><water transporter><wt-loss>