Vijayakumar Kakade, PhD
Research Scientist, Internal Medicine (Nephrology)Cards
Appointments
Contact Info
About
Titles
Research Scientist, Internal Medicine (Nephrology)
Biography
Dr. Kakade received his Ph.D in Biochemistry from University of Mysore, India. After completing his Ph.D, he entered a postdoctoral training at University of Kansas Medical Center, Kansas City, where his research focused on defining the candidate signals and sensors that regulate cell activation states in polycystic kidney disease. Dr. Kakade joined Yale University in 2016 where he established his research on the delineating the role of macrophages in cystogenesis in polycystic kidney disease and application of Imaging Mass Cytometry to understand the cell-cell interactions and cellular response involved in pathogenesis of human kidney diseases.
Appointments
Nephrology
Research ScientistPrimary
Other Departments & Organizations
- Cantley Lab
- Internal Medicine
- Nephrology
Education & Training
- PhD
- University of Mysore, Biochemistry (2013)
Research
Overview
The research goal is to understand the pathogenesis of polycystic kidney disease (PKD), a genetic disorder caused by mutations in either Pkd1 or Pkd2 genes, which encode polycystin 1 (PC1) and polycystin 2 (PC2) respectively, affecting the normal architecture of renal tubule, giving rise to ADPKD. Studies have uncovered the critical roles of polycystins and cilia in maintaining the three-dimensional structure of renal tubules. Understanding the mechanism and discovery of molecular determinants of cyst development and disease progression will advance the mechanism-based therapeutic target for the treatment of ADPKD. We have focused these efforts on delineating the role of Mcp1 in promoting macrophage-dependent cyst expansion in PKD and found that proinflammatory macrophages accumulate around the cyst and promote tubular epithelial cell injury. Subsequent switch to an alternative activation of macrophages promotes accelerated cyst growth due to an increase in tubular proliferative rates. High-resolution multiphoton imaging at the earliest phases of cyst formation following knock-out of Pkd1 showed that tubule dilation and epithelial proliferation occur simultaneously, and that dilation was more evident in tubules in which epithelial area had not increased implying proliferation is not a solitary force for tubule expansion. We are investigating the mechanism and the critical events that maintain the normal architecture of renal tubules and identify the critical components that are dysregulated in the absence of polycystins.
Imaging mass cytometry (IMC) is a technique that uses a high-resolution laser combined with a mass cytometer to detect the presence, location, and amount of up to 42 different heavy metal conjugated antibodies hybridized onto a tissue section. Our group has successfully developed IMC and a machine learning algorithm to identify resident kidney cell populations, infiltrating cell populations, and cell activation and injury states in human kidney tissue. Research is focused on the application of IMC and the analysis pipeline for 2D quantitative assessment of cell location, cell-cell interactions, and cellular responses in human kidney diseases.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Anand Reghuvaran, PhD
Dennis G Moledina, MD, PhD, FASN
F. Perry Wilson, MD, MSCE
Gilbert Moeckel, MD, PhD, FASN
John Pell
Lloyd G. Cantley, MD
Publications
2024
Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis
Barsotti G, Luciano R, Kumar A, Meliambro K, Kakade V, Tokita J, Naik A, Fu J, Peck E, Pell J, Reghuvaran A, Tanvir E, Patel P, Zhang W, Li F, Moeckel G, Perincheri S, Cantley L, Moledina D, Wilson F, He J, Menon M. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis. Kidney International Reports 2024, 9: 1354-1368. PMID: 38707807, PMCID: PMC11068976, DOI: 10.1016/j.ekir.2024.02.006.Peer-Reviewed Original ResearchAltmetricConceptsMinimal change diseaseRandomized controlled trialsSafety of metforminDouble-blindPodocyte injuryAdjunctive therapyPlacebo-controlled randomized controlled trialsPhase III studyPhase II trialPrimary glomerular diseaseFocal segmental glomerulosclerosisEffect of metforminPhase IIPlacebo-controlledPreclinical dataNovel urineChange diseaseTissue markersRandomized trialsSegmental glomerulosclerosisGlomerular diseaseMechanistic biomarkersObservational studyFSGSInexpensive agent
2016
Cyclic‐AMP Regulates Glycogen Synthase Kinase‐3β by a Feed‐Forward Mechanism in Polycystic Kidney Disease
Kakade V, Tao S, Zhou X, Li X, Pandey P, Rajagopal M, Rao R. Cyclic‐AMP Regulates Glycogen Synthase Kinase‐3β by a Feed‐Forward Mechanism in Polycystic Kidney Disease. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.968.28.Peer-Reviewed Original ResearchConceptsCRE-binding proteinGlycogen synthase kinase-3βCAMP response elementSynthase kinase-3βSerine/threonine protein kinaseGSK3β expressionKinase-3βCAMP-responsive genesThreonine protein kinasePolycystic kidney diseaseCyst expansionCAMP levelsPotential binding sitesFeed-forward loopInhibition of GSK3βResponsive genesTranscription factorsProtein kinaseFeed-forward mechanismResponse elementGSK3β proteinCell survivalCREB activityGSK3βActive GSK3β
Academic Achievements & Community Involvement
activity Frontiers in Medicine
Peer Review Groups and Grant Study SectionsReviewing EditorDetails11/14/2021 - Presentactivity Journal of Biomedical Nanotechnology
Peer Review Groups and Grant Study SectionsReviewerDetails2018 - Presentactivity Journal of Kidney
Peer Review Groups and Grant Study SectionsEditorial BoardDetails2018 - Presenthonor CSIR-Senior Research Fellow
International AwardCouncil of Scientific and Industrial ResearchDetails09/15/2008India