Boston University School of Medicine
Silvio Conte Building
72 E. Concord Street, K403
Boston, MA 02118
Lab Phone: 617-638-4717
BA, UCLA, Los Angeles, CA
PhD, Boston University, Boston, MA
Research Asst. Professor
| Jun Yu
Research Asst. Professor
Vascular disease of the heart, lung, kidney and the general circulation are the major cause of morbidity and mortality worldwide. Vascular disease is particularly crippling and the major cause of death among the elderly. It is in critical need of solution not only to prolong life span but also to improve the comfort of living.
Major causes of vascular malfunction are smooth muscle cell overgrowth, chronic contraction and blood vessels filled with unwanted deposits clogging blood flow. We are engaged in studies to stem this tide. Our aim is to attain vascular homeostasis in diseased, damaged blood vessels through control of signaling functions by the vasoactive receptors which are at the primary source of these physiologic malfunctions. These receptor include the endothelin-1 ETA and ETB receptors, angiotensin AT1 receptor, prostanoid receptors and certain tyrosine kinase receptors. We are determining the structure function relationship of these receptors. Using mutagenesis, cell permeable peptide techniques and transgenic mouse approaches. We have been locating specific motifs or combinations of motifs in these receptors which are responsible for specific damaging signals. We are now able to block some of these specific damaging signals using cell permeable peptides mimicking specific receptor motifs. We are also becoming aware of failures of beneficial signaling downstream of the vasoactive receptors. These failures are also being addressed.
- A cell permeable peptide targeting the intracellular loop 2 of endothelin B receptor reduces pulmonary hypertension in a hypoxic rat model. Green DS, Rupasinghe C, Warburton R, Wilson JL, Sallum CO, Taylor L, Yatawara A, Mierke D,Polgar P, Hill N. PLoS One. 2013 Nov 27;8(11):e81309.
- C-terminus of ET A /ETB receptors regulate endothelin-1 signal transmission. Yatawara A, Wilson JL, Taylor L, Polgar P, Mierke DF. J Pept Sci. 2013 Apr;19(4):257-62. doi: 10.1002/psc.2499. Epub 2013 Feb 25.
- Altered expression and signal transduction of endothelin-1 receptors in heritable and idiopathic pulmonary arterial hypertension. Yu J, Taylor L, Wilson J, Comhair S, Erzurum S, Polgar P. J Cell Physiol. 2013 Feb;228(2):322-9. doi: 10.1002/jcp.24132.
- Kao PF, Banigan MG, Vanderburg CR, McKee AC, Polgar P, Seshadri S, and Delalle I Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early Alzheimer’s disease pathology. Journal of Neuropathology and Experimental Neurology, 2012 Jul;71(7):654-64.
- Sallum CO, Wilson JL, Rupasinghe C, Berg E, Yu J, Green DS, Taylor L, Mierke D, Polgar P. Enhancing and limiting endothelin-1 signaling with a cell penetrating peptide mimicking the third intracellular loop of the ETB receptor. Chem Biol Drug Des. 2012 Sep;80(3):374-81.
- Wilson JL, Taylor L, Polgar P. Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint. Exp Cell Res. 2012 Jun 10;318(10):1125-33.
- Yu J, Taylor L, Rich C, Toselli P, Stone P, Green D, Warburton R, Hill N, Goldstein R, Polgar P. Transgenic expression of an altered angiotensin type I AT1 receptor resulting in marked modulation of vascular type I collagen. J Cell Physiol. 2012 May;227(5):2013-21.
- Erzurum S, Rounds SI, Stevens T, Aldred M, Aliotta J, Archer SL, Asosingh K, Balaban R, Bauer N, Bhattacharya J, Bogaard H, Choudhary G, Dorn GW 2nd, Dweik R, Fagan K, Fallon M, Finkel T, Geraci M, Gladwin MT, Hassoun PM, Humbert M, Kaminski N, Kawut SM, Loscalzo J, McDonald D, McMurtry IF, Newman J, Nicolls M, Rabinovitch M, Shizuru J, Oka M, Polgar P, Rodman D, Schumacker P, Stenmark K, Tuder R, Voelkel N, Sullivan E, Weinshilboum R, Yoder MC, Zhao Y, Gail D, Moore TM. Strategic plan for lung vascular research: An NHLBI-ORDR Workshop Report. Am J Respir Crit Care Med. 2010. 82(12):1554-62.
- Yu J, Taylor L, Mierke D, Berg E, Shia M, Fishman J, Sallum C, Polgar P. Limiting angiotensin II signaling with a cell-penetrating peptide mimicking the second intracellular loop of the angiotensin II type-I receptor. Chem Biol Drug Des. 2010,76:70-76, NIHMS245281
- Huang Z, Yu J, Toselli P, Bhawan J, Sudireddy V, Taylor L, Polgar P. Angiotensin II type 1 and Bradykinin B2 receptors expressed in early stage epithelial cells derived from human embryonic stem cells. J Cell Physiol. 211:816-825, 2007.
- Yu J, Lubinsky D, Tsomaia N, Huang Z, TaylorL, Mierke DM, Navarro J, Miraz, O, Polgar P : Activation of ERK, JNK, Akt and G-protein Coupled Signaling by Hybrid Angiotensin II AT1/Bradykinin B2 Receptors Expressed in HEK-293 Cells. J Cell Biochem 101:192-204, 2007.
- Huang Z, Taylor L, Lui B, Yu J, Polgar P. Modulation by bradykinin of angiotensin type 1 receptor-evoked rhoA activation of connective tissue growth factor expression in human lung fibroblasts. Am J Physiology-Lung,Cell and Mol Physiol. 290:L1291-1299, 2006.
- Liu B, Yu J, Taylor L, Zhou X, Polgar P. Microarray and phosphokinase screenings leading to studies on ERK and JNK regulation of connective tissue growth factor expression by angiotensin II 1a and bradykinin B2 receptors. J Cell Biochem. 97:1104-1120, 2006.
- Yu J, Polgar P, Lubinsky D, Gupta M, Wang L, Mierke D, Taylor L. Coulombic and hydrophobic interactions in the first intracellular loop are vital for bradykinin B2 receptor ligand binding and consequent signal transduction. Biochemistry. 44:5295-306, 2005.
- Piserchio, A., V. Zelesky, J. Yu, L. Taylor, P. Polgar, and D.F. Mierke. Bradykinin B2 receptor signaling: Structural and functional characterization of the C-terminus. Biopolymers. 80:367-73 2005
- Yu J, Liu B, Eramian D, Mierke D, Taylor L and Polgar P. K317, R319 and E320 within the proximal C-terminus of the bradykinin B2 receptor form a motif important for phospholipase C and phospholipase A2 but not connective tissue growth factor related signaling. J Cell Biochem 92:547-559, 2004
- Pal-Ghosh R, Yu J, Prado GN, Taylor L, Mierke DF, Polgar P. Chimeric exchanges within the bradykinin B2 receptor intracellular face with the prostaglandin EP2 receptor as the donor: importance of the second intracellular loop for cAMP synthesis Arch Biochem Biophys. 415:54-62, 2003
- Prado GN, Taylor L, Zhou X, Ricupero D, Mierke DF and Polgar P Mechanisms Regulating the Expression, Self-Maintenance and Signaling-Function of the Bradykinin B2 and B1 Receptors. J Cell Phys. 193:275-386, 2002.
- Yu J, Prado GN, Taylor L, Pal-Ghosh R, Polgar, P Hybrid formation between the intracellular faces of the bradykinin B2 and angiotensin II AT1 receptors and signal transduction. Int Immunopharmacol. 2:1807-1822, 2002.
- Yu J, Prado GN, Schreiber B, Polgar PJ, Polgar P and Taylor L. Role of Prostaglandin E2 EP Receptors and cAMP in the Expression of Connective Tissue Growth Factor. Arch Biochem Biophys 404:302-308, 2002
- Yu J, Prado GN, Taylor L, Piserchio A, Gupta A, Mierke DF, Polgar P. Global chimeric exchanges within the intracellular face of the bradykinin B2 receptor with corresponding angiotensin II type Ia receptor regions: generation of fully functional hybrids showing characteristic signaling of the AT1a receptor. J Cell Biochem 85:809-819, 2002.
- Piserchio A, Prado GN, Zhang R, Taylor L, Yu J, Polgar P, Mierke DF. Structural Insight into the Role of the Second Intracellular Loop of the Bradykinin B2 Receptor in Signaling and Internalization. Biopolymers 63:239-246, 2002.