Paula R. Clemens, Associate Professor
M.D., Medical College of Pennsylvania
Philadelphia, PA, 1984
Email: pclemens@pitt.edu
clemenspr@upmc.edu
Research Interests:
Skeletal muscle can be affected by inherited disorders due to single gene defects, such as the forms of muscular dystrophy, and by systemic disorders that cause muscle wasting or cachexia, such as cancer, HIV or other chronic systemic diseases. The pathology and pathways of muscle degeneration due to muscular dystrophy and cachexia share some features in common. Gene transfer to muscle cells in vivo has the potential to address both clinical entities.
The central focus of our laboratory is gene delivery to striated muscle. Multiple projects within the laboratory are aimed at overcoming the hurdles inherent in gene delivery designed for therapeutic intervention. Identifying and solving problems of gene delivery and persistence will ultimately lead to clinically relevant gene transfer for inherited and acquired muscle disorders. Projects within the laboratory include: 1) gene transfer to skeletal muscle for inherited muscular dystrophies and the treatment of muscle cachexia, 2) novel forms of gene delivery including intrauterine gene transfer and the development of targeted vectors to enhance muscle gene delivery, 3) the study of transgene and viral protein-induced cellular and humoral immune responses due to high-capacity adenoviral vector-mediated gene delivery to muscle, 4) development of high-capacity adenoviral and AAV vector systems designed for both therapeutic gene delivery and immune suppression.
Recent Publications
View
Dr. Clemens' publications on PubMed.
Bilbao R, Reay D, Hughes T, Biermann V, Volpers C, Goldberg L, Bergelson J, Kochanek S, Clemens PR. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors. Gene Ther 2003 Sep 8;10(21):1821-1829
Bilbao R, Reay DP, Koppanati BM, Clemens PR. Biocompatibility of adenoviral vectors in PVC tubing catheters with the presence or absence of the plasticizer di-2-ethylhexyl phthalate. J Biomed Mater Res 2004 Feb;69A:91-96
Jiang Z, Schiedner G, Gilchrist SC, Kochanek S, Clemens PR. CTLA4Ig delivered by high-capacity adenoviral vector induces stable expression of dystrophin in mdx mouse muscle. Gene Ther 2004 Oct;11(19):1453-1461
Jiang Z, Schiedner G, van Rooijen N, Liu C-C, Kochanek S, Clemens PR. Sustained muscle expression of dystrophin from a high-capacity adenoviral vector with systemic gene transfer of T cell costimulatory blockade. Mol Ther 2004 Oct;10(4):688-696
Bilbao R, Reay DP, Wu E, Zheng H, Biermann V, Kochanek S, Clemens PR. Comparison of high-capacity and first-generation adenoviral vector gene delivery to murine muscle in utero. Gene Ther 2005;12(1):39-47
Bilbao R, Reay DP, Li J, Xiao X, Clemens PR. Patterns of gene expression from in utero delivery of AAV serotype 1. Hum Gene Ther 2005 Jun;16(6): 678-684
Escolar DM, Buyse G, Henricson E, Leshner R, Florence J, Mayhew J, Tesi-Rocha C, Gorni K, Pasquali L, Patel KV, McCarter R, Huang J, Mayhew T, Bertorini T, Carlo J, Connolly AM, Clemens PR, Goemans N, Iannaccone ST, Igarashi M, Nevo Y, Pestronk A, Subramony SH, Vedanarayanan VV, Wessel H and the CINRG group. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 2005 Jul;58(1):151-155
Jiang Z, Clemens PR. Cellular caspase-8-like inhibitory protein (cFLIP) prevents inhibition of muscle cell differentiation induced by cancer cells. FASEB J 2006 Dec;20:E1979-E1989
Mayhew JE, Florence JM, Henricson EK, Leshner RT, McCarter, RJ, Escolar DM, the CINRG Investigators. Reliable surrogate outcome measures in multicenter clinical trials of Duchenne muscular dystrophy. Muscle Nerve 2007 Jan;35:36-42
Katsumata Y, Ridgway WM, Oriss T, Gu X, Chin D, Wu Y, Fertig N, Oury T, Vandersteen D, Clemens P, Camacho CJ, Weinberg A, Ascherman DP. Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. J Autoimmun 2007. In press.
