Vipul C. Chitalia MD, PhD
Professor, Nephrology
Graduate Faculty (Primary Mentor of Grad Students)
650 Albany St | (617) 414-1773vichital@bu.edu
vipul.chitalia@bmc.org
Sections
Nephrology
Centers
Whitaker Cardiovascular Institute
Evans Center for Interdisciplinary Biomedical Research
Biography
Our laboratory focuses on the role of post-translational modifications of proteins, especially polyubiquitnation of the key mediators of vascular pathologies in diseases such as cancer and renal failure. While these diseases are discrete, several fundamental biological processes remain similar. Through a highly collaborative network, our laboratory harnesses the power of various cellular and molecular biological tools, relevant animal models (zebrafish and mice), computational methods and machine-learning techniques and strives to validate these findings and hypotheses in humanized models or human samples from large data bases, which highlights the translational nature of our approach.
A. Vascular diseases in kidney failure: Close to 20 million Americans or 10% of US population suffer from the chronic kidney disease (CKD). Among plethora of cardiovascular manifestations, CKD patients are particularly at high risk for both venous and arterial thrombosis, especially after vascular injury (endovascular injury such as angioplasty or stents; and surgical injury such as arteriovenous fistula creation) in CKD patients. This area of CKD management warrants urgent investigation due to lack of risk predictors and CKD-specific therapeutic targets.
Renal failure results in the retention of several chemical compounds, which unleash cellular toxicity, and hence called uremic solutes/toxins. While investigating the molecular pathogenesis of uremic toxicity, our laboratory was the first to demonstrate the prothrombotic propensity of indolic uremic solutes, which inhibits the ubiquitination of tissue factor, a bona fide member of the extrinsic coagulation pathway. Further investigation revealed Aryl Hydrocarbon Receptor (AHR) pathway as a critical mediator of tissue factor ubiquitination and thrombosis. Leveraging the ligand and the mediator, our lab aims to gain a deeper understanding into the mechanism of this unique uremic thrombosis axis (uremic solutes- AHR- TF- thrombosis) and to develop biomarkers and novel compounds to improve the management of the CKD patients with thrombosis after interventions in various vascular beds including coronary artery and arteriovenous fistula, etc.
Thrombosis being a dynamic and the multicomponent process, our laboratory has taken a holistic approach, under the co-directorship of Drs. Chitalia and Ravid, the Department of Medicine of BUSM and established a Thrombosis and Hemostasis ARC, which is a multidisciplinary platform of cell and molecular biologists, clinicians (cardiologists, vascular medicine, nephrologists and hematologists), computational biologists, biomedical engineers and statisticians and mathematicians to investigate various facets of thrombosis. http://www.bumc.bu.edu/evanscenteribr/the-arcs/the-arcs/
B. Angiogenesis: Angiogenesis, a process of generation of novel blood vessel is fundamental during the development and in various diseases such as cancer. Wnt signaling, a highly conserved oncogenic pathway is critical in angiogenesis. Beta catenin is the prime mediator of Wnt activation. Focusing on the ubiquitination and proteasomal degradation of beta catenin, our previous work had described Jade-1, as an E3 ligases of wild-type beta catenin. Our recent efforts have specifically focused on c-Cbl as an E3 ligase for the mutant beta catenin and for the transcriptionally active beta catenin in the nucleus. These two species of beta catenin, once considered resistant to degradation are effectively downregulated by c-Cbl. Thus, c-Cbl is a unique E3 ligase of tumorigenic beta catenin, which is involved in several cancers including colorectal cancer pathogenesis. Leveraging the cancer animal models and human cancer samples including machine learning based quantitative histology! techniques, our group investigates the colorectal cancer pathogenesis to gain deeper understanding of the role of E3 ligases of beta catenin E3 ligases in various cancers.
Websites
Hariri Institute for Computing and Computational Science & Engineering
Education
MD, Seth G.S. Medical College
MBBS, Lokmanya Tilak Medical College and Hospital
Molecular Medicine, PhD, Boston University School of Medicine
DM, Seth G.S. Medical College
Publications
Lin W, Mousavi F, Blum BC, Heckendorf CF, Moore J, Lampl N, McComb M, Kotelnikov S, Yin W, Rabhi N, Layne MD, Kozakov D, Chitalia VC, Emili A. Corrigendum: Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease. Front Pharmacol. 2024; 15:1376058. PMID: 38405670.
Published on 1/17/2024Smeds MR, Cheng TW, King E, Williams M, Farber A, Chitalia VC, Siracuse JJ. Characterization of long-term survival in Medicare patients undergoing arteriovenous hemodialysis access. J Vasc Surg. 2024 Jan 17. PMID: 38237702.
Published on 1/5/2024Lotfollahzadeh S, Yang X, Wu Wong DJ, Han J, Seta F, Ganguli S, Jose A, Ravid K, Chitalia VC. Venous Thrombosis Assay in a Mouse Model of Cancer. J Vis Exp. 2024 Jan 05; (203). PMID: 38251710.
Published on 12/16/2023Zhu M, Arinze N, Buitron de la Vega P, Alonso A, Levin S, Farber A, King E, Kobzeva-Herzog A, Chitalia VC, Siracuse JJ. High Prevalence of Adverse Social Determinants of Health in Dialysis Access Creation Patients in a Safety-Net Setting. Ann Vasc Surg. 2024 Mar; 100:31-38. PMID: 38110081.
Published on 11/27/2023Lin W, Mousavi F, Blum BC, Heckendorf CF, Moore J, Lampl N, McComb M, Kotelnikov S, Yin W, Rabhi N, Layne MD, Kozakov D, Chitalia VC, Emili A. Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease. Front Pharmacol. 2023; 14:1243505. PMID: 38089059.
Published on 9/22/2023Levin SR, Alonso A, Salazar ED, Farber A, Chitalia VC, King EG, Cheng TW, Siracuse JJ. Recent evaluation by nephrologists is associated with decreased incidence of tunneled dialysis catheter being used at the time of first arteriovenous access creation. J Vasc Surg. 2024 Jan; 79(1):128-135. PMID: 37742733.
Published on 9/5/2023Belghasem M, Yin W, Lotfollahzadeh S, Yang X, Meyer RD, Napoleon MA, Sellinger IE, Vazirani A, Metrikova E, Jose A, Zhebrun A, Whelan SA, Lee N, Rahimi N, Chitalia VC. Tryptophan Metabolites Target Transmembrane and Immunoglobulin Domain-Containing 1 Signaling to Augment Renal Tubular Injury. Am J Pathol. 2023 Oct; 193(10):1501-1516. PMID: 37676196.
Published on 6/17/2023Idrees N, Haroon S, Zhang Y, Mangio JC, Siracuse JJ, Francis JM, Ganguli S, Daly K, Diamond M, Vilvendhan R, Cabral H, Dember LM, Farber A, Kolachalama VB, Chitalia VC. Contrast Venography Versus Intravenous Ultrasound in Hemodialysis Arteriovenous Access Dysfunction. Kidney Int Rep. 2023 Sep; 8(9):1887-1891. PMID: 37705907.
Published on 6/8/2023Budbazar E, Sulser Ponce De Leon S, Tsukahara Y, Liu H, Huangfu Y, Wang Y, Seabra PM, Yang X, Goodman JB, Wan X, Chitalia V, Han J, Seta F. Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome. Arterioscler Thromb Vasc Biol. 2023 Aug; 43(8):e339-e357. PMID: 37288573.
Published on 6/1/2023Martens KL, Li A, La J, May SB, Swinnerton KN, Tosi H, Elbers DC, Do NV, Brophy MT, Gaziano JM, Lotfollahzadeh S, Chitalia V, Ravid K, Fillmore NR. Epidemiology of Cancer-Associated Venous Thromboembolism in Patients With Solid and Hematologic Neoplasms in the Veterans Affairs Health Care System. JAMA Netw Open. 2023 Jun 01; 6(6):e2317945. PMID: 37306999.
Media Mentions
Published on 9/6/2023
Gene Linked to Chronic Kidney Disease Could Be New Therapy Target
Published on 11/2/2021
Pathway and enzyme responsible for CKD thrombosis identified
Published on 11/2/2021
Enzyme Helps Unravels the Mystery of Thrombosis in Chronic Kidney Disease
Published on 11/1/2021
Researchers identify an important mediator of thrombosis in CKD patients
Published on 9/13/2021
Why Are Black Cancer Patients at Higher Risk for Blood Clots?
Published on 1/3/2020
A New PD-1 Regulatory Protein in Colorectal Cancer
Published on 12/30/2019
Black Patients at Higher Risk for Cancer-Associated Venous Thromboembolism
Published on 12/17/2019
African Americans With Cancer Have Higher Risk Of Blood Clots
Published on 11/25/2019
New Insights Into Blood Clot Mechanisms in Cancer Patients Discovered
Published on 5/29/2019
Know What’s Good for your Health? Artificial Intelligence
View full list of 11 media mentions.