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, Graduate Medical Sciences
- Active Staff Hospital Privileges, Medicine, Boston Medical Center
- Assistant Professor, Radiology, Boston University School of Medicine
- Associate Professor, Pathology & Laboratory Medicine, Boston University School of Medicine
- BU Profile
- Chitalia Lab
- Press Release: Key Protein
- ThromboARC (Dept of Medicine)
- Collaborator: Edelman Lab
- Collaborator: Ravid lab
- Collaborator: Rahimi lab
- Collaborator: Sherr lab
- Collaborator: Kolachalama lab
- Hariri Institute for Computing and Computational Science & Engineering
- Boston Medical Center Physician Provider Profile
- Seth G.S. Medical College, MD
- Lokmanya Tilak Medical College and Hospital, MBBS
- Seth G.S. Medical College, DM
- Published on 6/7/2019
Leiva O, Bekendam RH, Garcia BD, Thompson C, Cantor A, Chitalia V, Ravid K. Emerging Factors Implicated in Fibrotic Organ-Associated Thrombosis: The Case of Two Organs. TH Open. 2019 Apr; 3(2):e165-e170. PMID: 31259299.
- Published on 5/23/2019
Lyle CL, Belghasem M, Chitalia VC. c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis. Cells. 2019 May 23; 8(5). PMID: 31126146.
- Published on 5/9/2019
Belghasem ME, A'amar O, Roth D, Walker J, Arinze N, Richards SM, Francis JM, Salant DJ, Chitalia VC, Bigio IJ. Towards minimally-invasive, quantitative assessment of chronic kidney disease using optical spectroscopy. Sci Rep. 2019 May 09; 9(1):7168. PMID: 31073168.
- Published on 5/2/2019
Chang GH, Azar DA, Lyle C, Chitalia VC, Shazly T, Kolachalama VB. Intrinsic coating morphology modulates acute drug transfer in drug-coated balloon therapy. Sci Rep. 2019 May 02; 9(1):6839. PMID: 31048704.
- Published on 4/15/2019
Kannan S, Morgan LA, Liang B, Cheung MG, Lin CQ, Mun D, Nader RG, Belghasem ME, Henderson JM, Francis JM, Chitalia VC, Kolachalama VB. Segmentation of Glomeruli Within Trichrome Images Using Deep Learning. Kidney Int Rep. 2019 Jul; 4(7):955-962. PMID: 31317118.
- Published on 3/1/2019
Arinze NV, Gregory A, Francis JM, Farber A, Chitalia VC. Unique aspects of peripheral artery disease in patients with chronic kidney disease. Vasc Med. 2019 06; 24(3):251-260. PMID: 30823859.
- Published on 7/17/2018
Kumaradevan S, Lee SY, Richards S, Lyle C, Zhao Q, Tapan U, Jiangliu Y, Ghumman S, Walker J, Belghasem M, Arinze N, Kuhnen A, Weinberg J, Francis J, Hartshorn K, Kolachalama VB, Cifuentes D, Rahimi N, Chitalia VC. c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/ß-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation. Am J Pathol. 2018 08; 188(8):1921-1933. PMID: 30029779.
- Published on 4/1/2018
Reddy YNV, Nunes D, Chitalia V, Gordon CE, Francis JM. Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents. Hemodial Int. 2018 04; 22 Suppl 1:S53-S60. PMID: 29694721.
- Published on 1/17/2018
Kolachalama VB, Shashar M, Alousi F, Shivanna S, Rijal K, Belghasem ME, Walker J, Matsuura S, Chang GH, Gibson CM, Dember LM, Francis JM, Ravid K, Chitalia VC. Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans. J Am Soc Nephrol. 2018 03; 29(3):1063-1072. PMID: 29343519.
- Published on 1/11/2018
Kolachalama VB, Singh P, Lin CQ, Mun D, Belghasem ME, Henderson JM, Francis JM, Salant DJ, Chitalia VC. Association of Pathological Fibrosis With Renal Survival Using Deep Neural Networks. Kidney Int Rep. 2018 Mar; 3(2):464-475. PMID: 29725651.
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