KRISTEN W. LYNCH, Ph.D.
Associate Professor of Biochemistry and Biophysics

909B Stellar-Chance Labs
422 Curie Boulevard
Philadelphia, PA 19104-6059
(215) 573-7749 (office)
(215) 215-573-7756 (lab)
klync@mail.med.upenn.edu

Recent insight into the human genome has revealed that most genes encode multiple distinct protein isoforms through the process of alternative pre-mRNA splicing.  My laboratory is focused on understanding the biochemical mechanisms and regulatory networks that control alternative splicing in response to antigen-challenge of the human immune system. Recently we have identified ~150 genes that exhibit an alteration in isoform expression in response to T cell stimulation. Through our initial work on the regulated splicing of the protein tyrosine phosphatase CD45, we have identified the regulatory sequence, proteins that controls activation-induced isoform expression of CD45 as well as exons in several other genes essential for T cell function.  This work is on-going as we seek to understand the mechanism of this regulation at molecular and atomic detail.  We are also expanding our focus to include additional networks of co-regulated splicing events in T cells.  Together these studies are providing new insights into the mechanisms and consequences of RNA-based gene regulation in the cellular response to environmental stimuli.

RECENT REPRESENTATIVE PUBLICATIONS:

Topp J.D., J. Jackson, A.A. Melton, and K.W. Lynch (2008) A cell-based screen for splicing regulators identifies hnRNP LL as a distinct signal-induced repressor of CD45 variable exon 4. RNA 14: 2038-2049.

Melton, A.A., J. Jackson, J. Wang, and K.W. Lynch. (2007) Combinatorial control of signal-induced exon repression by hnRNP L and PSF. Mol. Cell. Biol. 27:6972-6984.

Ip, J., A. Tong, Q. Pan, J. Topp, B.J. Blencowe, and K.W. Lynch (2007) Global analysis of alternative splicing during T cell activation. RNA 13:563-572.

House, A.E. and K.W. Lynch. (2006) An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition. Nat. Struct. Mol. Biol. 13: 937-944.

Tong, A., J. Nguyen, and K.W. Lynch (2005) Differential expression of CD45 isoforms is controlled by the combined activity of basal and inducible splicing regulatory elements in each of the variable exons. J. Biol. Chem. 280:38297-304.

Rothrock, C.R., A.E. House, and K.W. Lynch (2005) HnRNP L represses exon splicing via a regulated exonic splicing silencer. EMBO J 24:2792-2802.

Rothrock, C., B. Cannon, B. Hahm and K.W. Lynch (2003) A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. Molecular Cell 12:1317-1324.