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.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Active Staff Hospital Privileges, Medicine, Boston Medical Center
- Seth G.S. Medical College, MD
- Lokmanya Tilak Medical College and Hospital, MBBS
- Seth G.S. Medical College, DM
- Published on 9/18/2017
Woolf N, Pearson BE, Bondzie PA, Meyer RD, Lavaei M, Belkina AC, Chitalia V, Rahimi N. Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy. Oncogenesis. 2017 Sep 18; 6(9):e378. PMID: 28920928.
- Published on 7/15/2017
Gordon CE, Chitalia VC, Sloan JM, Salant DJ, Coleman DL, Quillen K, Ravid K, Francis JM. Thrombotic Microangiopathy: A Multidisciplinary Team Approach. Am J Kidney Dis. 2017 Nov; 70(5):715-721. PMID: 28720207.
- Published on 6/7/2017
Abbonante V, Chitalia V, Rosti V, Leiva O, Matsuura S, Balduini A, Ravid K. Upregulation of lysyl oxidase and adhesion to collagen of human megakaryocytes and platelets in primary myelofibrosis. Blood. 2017 Aug 10; 130(6):829-831. PMID: 28592432.
- Published on 5/21/2017
Tapan U, Lee SY, Weinberg J, Kolachalama VB, Francis J, Charlot M, Hartshorn K, Chitalia V. Racial differences in colorectal cancer survival at a safety net hospital. Cancer Epidemiol. 2017 Aug; 49:30-37. PMID: 28538169.
- Published on 11/1/2016
Shashar M, Siwak J, Tapan U, Lee SY, Meyer RD, Parrack P, Tan J, Khatami F, Francis J, Zhao Q, Hartshorn K, Kolachalama VB, Rahimi N, Chitalia V. c-Cbl mediates the degradation of tumorigenic nuclear ß-catenin contributing to the heterogeneity in Wnt activity in colorectal tumors. Oncotarget. 2016 11 01; 7(44):71136-71150. PMID: 27661103.
- Published on 9/2/2015
Arafa E, Bondzie PA, Rezazadeh K, Meyer RD, Hartsough E, Henderson JM, Schwartz JH, Chitalia V, Rahimi N. TMIGD1 is a novel adhesion molecule that protects epithelial cells from oxidative cell injury. Am J Pathol. 2015 Oct; 185(10):2757-67. PMID: 26342724.
- Published on 6/10/2015
Srinivasan S, Chitalia V, Meyer RD, Hartsough E, Mehta M, Harrold I, Anderson N, Feng H, Smith LE, Jiang Y, Costello CE, Rahimi N. Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis. 2015 Oct; 18(4):449-62. PMID: 26059764.
- Published on 5/27/2015
Shivanna S, Kolandaivelu K, Shashar M, Belghasim M, Al-Rabadi L, Balcells M, Zhang A, Weinberg J, Francis J, Pollastri MP, Edelman ER, Sherr DH, Chitalia VC. The Aryl Hydrocarbon Receptor is a Critical Regulator of Tissue Factor Stability and an Antithrombotic Target in Uremia. J Am Soc Nephrol. 2016 Jan; 27(1):189-201. PMID: 26019318.
- Published on 3/25/2015
Vipul Chitalia. Good-in-good-out: Diet modification in chronic kidney disease. Science Translational Medicine. 2015; 7(280):280.
- Published on 3/17/2015
Shivanna S, Harrold I, Shashar M, Meyer R, Kiang C, Francis J, Zhao Q, Feng H, Edelman ER, Rahimi N, Chitalia VC. The c-Cbl ubiquitin ligase regulates nuclear ß-catenin and angiogenesis by its tyrosine phosphorylation mediated through the Wnt signaling pathway. J Biol Chem. 2015 May 15; 290(20):12537-46. PMID: 25784557.
View 26 more publications: View full profile at BUMC