Jeffrey D. Alexis, M.D.

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Contact

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 679
Rochester, New York 14642

Office: 585 276-9795 (primary)

Lab: 585 276-9845

Fax: 585 276-9830

Portrait

Research in Dr. Alexis' lab focuses on signaling pathways that regulate intimal proliferation. Intimal proliferation occurs in several pathologic states including transplant arteriopathy and restenosis following angioplasty. Smooth muscle cell inflammation and proliferation are important aspects of this pathology. Our research focuses on the role of breakpoint cluster region (Bcr) in the development of intimal proliferation. Bcr was first identified for its role as part of the Philadelphia chromosome in chronic myelogenous leukemia. Bcr is also a serine/threonine kinase. We have demonstrated that Bcr plays a role in vascular wall intimal proliferation. We have shown that Bcr regulates both inflammation and proliferation in vascular smooth muscle cells (VSMC). Specifically, we have shown that dominant negative Bcr reversed Angiotensin II-mediated inhibition of the transcription factor PPAR gamma. We have found that Angiotensin II increases Bcr expression and kinase activation. We have shown that Bcr is present in the nucleus of smooth muscle cells and phosphorylates PPAR gamma. We have also shown that Bcr inhibits PPAR gamma transcriptional activation. This inhibition is via phosphorylation of PPAR gamma at S82, the site at which ERK 1/2 phosphorylates PPAR gamma (also leading to inhibition of PPAR gamma). Our data also demonstrate that Bcr enhances NF-kB transcriptional activity at least in part via inhibition of PPAR gamma. Intimal proliferation in low-flow carotid arteries was reduced in Bcr knockout mice compared with controls, demonstrating a critical role of Bcr on VSMC proliferation in vivo. Our current work focuses on Bcr signaling independent of PPAR gamma. We have identified the splicing factor UAP56 as another Bcr kinase substrate and we are now investigating the role of UAP56 in cellular proliferation.

Current Appointments

Education
MD Medicine Harvard Medical School 1992
BA Mathematics Harvard College (Cum laude) 1988
Post-Doctoral Training & Residency
Cardiology Fellow, Mount Sinai Medical Center, New York, New York 1995 - 1998
Internal Medicine Resident, Massachusetts General Hospital, Boston, MA 1992 - 1995
Fellowship Awards
Robert Wood Johnson Foundation Minority Medical Faculty Development Grant Signaling Pathways as Targets for Transplant Arteriopathy Principal Investigator: Jeffrey Alexis, MD ID Number: 038404 Total cost $365,400 70% Effort 2000 - 2005
National Research Service Award-Individual Award National Institutes of Health G Proteins as Targets for Transplant Arteriopathy Principal Investigator: Jeffrey Alexis, MD Assignment Number: 1 F32HL 10225-01 Total direct cost $41,967 1999 - 2000
John C. Sable Memorial Heart Fund, Inc. Award The Effect of Rapamycin on Transplant Arteriopathy. Principal Investigator: Jeffrey Alexis, MD Total direct cost $12,000 1998 - 1999
National Research Service Award-Institutional Award National Institutes of Health The Effect of Rapamycin on Transplant Arteriopathy. Principal Investigator: Mark Taubman, MD Assignment Number: HL07824-01 Total direct cost $31,476 1998 - 1999

Lab Website

http://www.urmc.rochester.edu/cvri/research/alexis-lab.cfm

Recent Journal Articles
Showing the 5 most recent journal articles. (7 available)
Alexis, J.D.; Wang, N.; Che, W.; Lerner-Marmarosh, N.; Sahni, A.; Korshunov, V.A.; Zou, Y.; Ding, B.; Yan, C.; Berk, B.C.; Abe, J. "Bcr kinase activation by Angiotensin II inhibits PPARg transcriptional activity in vascular smooth muscle cells." Circulation Research 104 (2009): 69-78.
Alexis,J.D.; Pyo,R.T.; Chereshnev,I.; Katz J.; Rollins,B.J.; Charo I.F.; Taubman,M.B. "Inhibition of MCP-1/CCR2 signaling does not inhibit intimal proliferation in a mouse aortic transplant model." Journal of Vascular Research 45 (2008): 538-546.
Strain,J. J.; Karim,A.; Caliendo,G.; Alexis,J. D.; Lowe,R. S.,3rd; Fuster,V. "Cardiac drug-psychotropic drug update". General Hospital Psychiatry 24 (2002): 283-289.
Strain,J. J.; Caliendo,G.; Alexis,J. D.; Lowe,R. S.,3rd; Karim,A.; Loigman,M. "Cardiac drug and psychotropic drug interactions: significance and recommendations." General Hospital Psychiatry 21 (1999): 408-429.
*Freudenberger,R.; *Alexis,J.; Gass,A.; Fuster,V.; Badimon,J. "Antithrombotic effect of FK 506 versus cyclosporine in cardiac transplant recipients: potential implications in transplant arteriopathy." The Journal of Heart and Lung Transplantation: the official publication of the International Society for Heart Transplantation 18 (1999): 1228-31. *Contributed equally to this work..