David A. Dean, Ph.D.

David A. Dean, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 651
Rochester, NY 14642

Office: (585) 276-3933
Administrative: (585) 275-5948
Lab: (585) 275-3577
Office: (585) 756-7780

Research Bio

Despite all of the hype regarding gene therapy, at present, gene therapy is a dream due to insufficient levels of gene transfer and expression at desired sites. One way to increase gene expression is to target more DNA to the cell nucleus. Since the nucleus is the site of transcription, without the movement of plasmids through the cytoplasm, translocation into the nucleus, and localization to the appropriate subnuclear domain, no gene expression, or "gene therapy" can take place. Ongoing projects in my laboratory are studying the mechanisms of cytoplasmic trafficking of plasmids along the cytoskeleton, plasmid nuclear entry, subnuclear organization, and exploiting what we learn to improve gene therapy.




We have shown that plasmids are able to enter the nucleus in a sequence-specific manner that appears to be mediated by transcription factor binding. My lab is interested in identifying the proteins required for this activity and the regulation of their nuclear import. Based on our model, we have created cell-specific plasmids by incorporating DNA sequences that bind to cell-specific transcription factors. At present, we have examples of smooth muscle, alveolar epithelial cell, and endothelial cell-targeting vectors that we hope to use for the treatment of a number of pulmonary diseases, and we are working to expand our repertoire to selectively target expression to any desired cell or tissue.


We also are developing methods for extracellular delivery of non-viral vectors in animal models for disease. Using electroporation, we have obtained very high levels of gene expression in the vasculature and lungs of animals. We have used this approach to prevent and/or cure existing disease in models of acute lung injury and asthma in mice and rats. Our next goal is to optimize these approaches in more relevant preclinical models to move toward clinical application.

Awards & Honors (Local)

Mentoring the Mentors, Searle Center for Teaching Excellence, Northwestern University 2006
Sandler Program for Asthma Research, Unsolicited conversion of Junior Investigator Award status to Senior Investigator Award based on research productivity 2005
NIH Individual Postdoctoral Fellowship (NRSA) 1991 - 1994
Presidents Undergraduate Scholarship, University of California, San Diego 1984

Recent Journal Articles

Showing the 5 most recent journal articles. 70 available »

2013 Oct
Dean DA. "Cell-specific targeting strategies for electroporation-mediated gene delivery in cells and animals." The Journal of membrane biology. 2013 Oct; 246(10):737-44. Epub 2013 Mar 24.
2013 Jun
Badding MA, Dean DA. "Highly acetylated tubulin permits enhanced interactions with and trafficking of plasmids along microtubules." Gene therapy.. 2013 Jun; 20(6):616-24. Epub 2012 Sep 27.
2011 Jul
Lin X, Dean DA. "Gene therapy for ALI/ARDS." Critical care clinics. 2011 Jul; 27(3):705-18.
2011 Feb
Eldib M, Dean DA. "Cyclic stretch of alveolar epithelial cells alters cytoskeletal micromechanics." Biotechnology and bioengineering. 2011 Feb; 108(2):446-53.
2010 Sep
Staversky RJ, Vitiello PF, Yee M, Callahan LM, Dean DA, O'Reilly MA. "Epithelial ablation of Bcl-XL increases sensitivity to oxygen without disrupting lung development." American journal of respiratory cell and molecular biology.. 2010 Sep; 43(3):376-85. Epub 2009 Oct 30.

Current Appointments

Professor - Department of Pediatrics, Neonatology (SMD) - Primary
Professor - Department of Biomedical Engineering (SMD)

Education

PhD | Microbiology | University of California at Berkeley1990
BA | Biochemistry | University of California at San Diego1985

Post-Doctoral Training & Residency

University of California, Los Angeles Postdoctoral Fellow Virology 1994