David A. Dichek, M.D., FAHA

Department of Medicine
Division of Cardiology
University of Washington, Seattle

Primary Research:
The lab is working on three projects: 1) Gene therapy for atherosclerosis; 2) Role of TGF-Β signaling in vascular homeostasis and disease; and 3) vascular protease activity and atherosclerosis.  To develop gene therapy for atherosclerosis we use helper-dependent adenoviral vectors (vectors that lack all viral genes) to express genes that prevent and reverse lipid accumulation in blood vessels.  These experiments are carried out in fat-fed rabbits and include experiments in arteries as well as grafted veins.  For our work on TGF-Β signaling we use mice in which transgenes are introduced that alter TGF-Β signaling in the vasculature.   We use genetically modified mice with altered protease expression as well as human atherosclerotic plaque tissue to investigate roles for vascular protease activity in atherosclerosis and plaque rupture.

Recent Publication:
J.H. Hu, H. Wei, M. Jaffe, N. Airhart, L. Du, S.N. Angelov, J. Yan, J.K. Allen, I. Kang, T. Wight, K. Fox, A. Smith, R. Enstrom, and D.A. Dichek.  Postnatal deletion of the type II TGF-beta receptor in smooth muscle cells causes severe aortopathy in mice.  Arterioscler Thromb Vasc Biol 2015; 35:2647–2656.  PMCID PMC4743752

J.H. Hu, P. Touch, J. Zhang, H. Wei, S. Liu, I.K. Lund, G. Hoyer-Hansen, and D.A. Dichek.  Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor.  Cardiovasc Res 2015; 105:372–382  PMCID: PMC4351369

L. Du, J. Zhang, A. Clowes, and D.A. Dichek.  Efficient gene transfer and durable transgene expression in grafted rabbit veins.  Hum Gene Ther 2015; 26:47–58.  PMCID PMC4303019.

R. Flynn, K. Qian, C. Tang, N. Dronadula, J. Buckler, B. Jiang, S. Wen, H.L. Dichek, and D.A. Dichek.  Expression of apolipoprotein A-I in rabbit carotid endothelium protects against atherosclerosis.  Mol Ther 2011; 19:1833–1841. PMCID: PMC3188740

J.H. Hu, L. Du, T. Chu, G. Otsuka, N. Dronadula, M. Jaffe, S.E. Gill, W.C. Parks, and D.A. Dichek. Overexpression of urokinase by plaque macrophages causes histologic features of plaque rupture and increases vascular MMP activity in aged apo E-null mice. Circulation 2010;121:1637–1644. PMCID: PMC2872172

Lab URL: http://depts.washington.edu/cardvr/DichekLab.html

Lab Members:
Faculty
Nagadhara Dronadula (Acting Instructor)

Staff
Lianxiang Bi (Research Scientist)
Jie Hong Hu (Research Scientist)
Brad Wacker (Research Scientist)
Julia Feyk (Administrative Assistant)

Postdoctoral Fellows
Stoyan Angelov
Alexis Stamatikos
Hao Wei

Undergraduate Students
Emma Beuren (Microbiology/English)
Rachel Enstrom (Neurobiology)
Kate Fox (Bioengineering)
Ervin Ham (Bioengineering)
Meena Sethuraman (Molecular Cellular and Developmental Biology)
Minghui Shi (Bioengineering)
Alexandra Smith (Biology)

Visiting Scientist
Ilkay Alp Yidirim

Collaborative Relationships:
Ben Cravatt, Scripps Research Institute
Cecilia Giachelli, University of Washington
Jay Heinecke, University of Washington
Gunilla Hoyer-Hansen, Finsen Laboratory
Ted Kohler, University of Washington
Ida Lund, Finsen Laboratory
Tomas Vaisar, University of Washington

Recent Presentations: 
AHA Scientific Conference on Arteriosclerosis Thrombosis and Vascular Biology/Peripheral Vascular Disease, San Francisco, CA; May, 2015

American Society of Gene and Cell Therapy, New Orleans, LA; May 2015

Lab Motto:  “In God We Trust; All Others Must Show Data”