Uremic vascular disease (Dr. Chitalia)

Vascular disease is the major cause of morbidity and mortality in the chronic renal failure (CRF) patients. However, there is lack of information about the molecular pathogenesis of how uremic milieu affects the endothelial and vascular biology. Dialysis access such as arterio-venous fistula is the life-line of patients with end stage renal disease (ESRD). Very little is known about the molecular mechanisms leading to AVF failure. The main objective of this project is to discern the molecular basis of vascular disease in uremic patients. We use endothelial cells as a model and intracellular signaling pathways perturbed in uremic environment are examined by proteomics and genetic approaches. This will act as a model for assessing different molecular pathways in various vascular cell-types. We then integrate the interplay of signaling pathways of vascular cell types in order to obtain a clear understanding of vascular disease, especially of AVF, in the patients with CRF. These studies in general will aid in the development of novel diagnostic and therapeutic strategies for vascular disease in CRF patients.

References:

1. Chitalia VC, Wells EJ, Robson RA, Searle M, Lynn KL. Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. Kidney International, Vol 56, 2236-2242, 1999

2. Chitalia VC, Kothari J, Wells EJ, Livesey JH, Robson RA, Searle M, Lynn KL. Cost-benefit analysis and predicting 24 hour proteinuria from the spot urine protein-creatinine ratio. Clinical Nephrology, Vol 55, 436-447, 2001

3. Chitalia V C, Almeida A F, Rai H, Bapat M, Chitalia K V, Acharya V N, Khanna R. Is peritoneal dialysis adequate for hypercatabolic acute renal failure in developing countries? Kidney International Vol. 61,747-757, 2002

4. Zhou M, Foy R, Chitalia VC, Panchenko M, Cohen H. Jade-1, a candidate renal tumor suppressor that promotes apoptosis. Proceedings of National Academy of Science Vol. 102, 11035-11040, 2005

5. Chitalia VC, Foy R, Zeng L, Panchenko MV, Zhou MI, Bharati A, Seldin DC, Lecker SH, Dominguez I., and Cohen HT. Jade-1 negatively regulates Wnt signaling by ubiquitinating β-catenin and mediates pVHL regulation of Wnt signaling. Nature Cell Biology Vol. 10, 1208-1216, 2008

6. Rebecca L. Foy, Ihn Young Song, Vipul C. Chitalia, Herbert T. Cohen, Nehme Saksouk, Christelle Cayrou, Vaziri Cyrus, Jacques Côté, and Maria V. Panchenko. Role of Jade-1 in HAT1 HBO Complex. Journal of Biological Chemistry Advanced online published)

7. Rebecca Foy, Vipul C. Chitalia, Maria Panchenko, Liling Zeng, Alessendra Boletta, Feng Qian, Leonidas Tsikoas, Gregory G. Germino, Mina I. Zhou, and Herbert T. Cohen. Polycystin-1 regulates the stability and ubiquitination of transcriptional coactivator Jade-1. (submitted)

Primary teaching affiliate
of BU School of Medicine