BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Lynch, Kristen Wood Associate Professor eRA COMMONS USER NAME klynch EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Harvard University Harvard University University of California, San Francisco DEGREE (if applicable) BA Ph.D. YEAR(s) 1990 1996 1997-2001 FIELD OF STUDY Biochemistry Biochemistry Immunology Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. A. Positions and Honors Research Positions 1989-1990 Undergraduate Research Laboratory of Prof. Mark Ptashne, Harvard University 1992-1996 Graduate Student Laboratory of Prof. Tom Maniatis, Harvard University 1997-2001 Postdoctoral Fellow Laboratory of Prof. Arthur Weiss, UC, San Francisco 2001-2007 Assistant Professor Department of Biochemistry, UT Southwestern Medical Center 2007-2009 Associate Professor Department of Biochemistry, UT Southwestern Medical Center 2009-present Associate Professor Department of Biochemistry and Biophysics University of Pennsylvania School of Medicine Honors and Awards 1991-1994 National Science Foundation Pre-doctoral Fellowship 1999-2001 Cancer Research Institute Post-doctoral Fellowship 2001-2009 E.E. and Greer Garson Fogelson Scholar in Biomedical Research UTSWMC Endowed Scholar Program 2004-2009 National Science Foundation Career Award B. Peer-Reviewed Publications Topp J.D., J. Jackson, A.A. Melton, 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. House, A.E. and K.W. Lynch (2008) Regulation of alternative splicing: more than just the ABCs. J. Biol. Chem. 18: 1217-1221. 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. (* co-corresponding authors) 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. Johnson, E.B., D.J. Steffen, K. W. Lynch, and J. Herz. (2006) Defective splicing of MEGF7/LRP4, a regulator of distal limb development, in autosomal recessive Mulefoot disease. Genomics 88: 600-609. Levinson, N., R. Hinman, A. Patil, C.R.J. Stephenson, S. Werner, G.H.C. Woo, J. Xiao, P. Wipf and K.W. Lynch (2006) Use of transcriptional synergy to augment sensitivity of a splicing reporter assay. RNA 12:925-930. 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. (* co-first authors) Lynch, K.W. (2004) Consequences of regulated pre-mRNA splicing in the immune system. Nat Rev Immunol. 4: 931-940. Rothrock, C., B. Cannon, B. Hahm and K.W. Lynch (2003) A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. Mol. Cell 12: 1317-1324. Sheives, P. and K.W. Lynch (2002) Identification of cells deficient in signaling-induced alternative splicing by use of somatic-cell genetics. RNA 8:1473-1481. Lynch, K.W. and A. Weiss (2001) A CD45 polymorphism associated with multiple sclerosis disrupts an exonic splicing silencer. J. Biol. Chem. 276: 24341-24347. Lynch, K.W. and A. Weiss (2000) A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras. Mol Cell Biol 20: 70-80. Hertel, K.J., K.W. Lynch and T. Maniatis (1997) Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol. 9: 350-357. Hertel, K.J., K.W. Lynch, E. C. Hsiao, E. H.-T. Liu and T. Maniatis (1996) Structural and functional conservation of the Drosophila doublesex splicing enhancer repeat elements. RNA 2: 969-981. Lynch, K.W. and T. Maniatis (1996) Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer. Genes & Dev. 10: 2089-2101. Lynch, K.W. and T. Maniatis (1995) Synergistic interactions between two distinct elements of a regulated splicing enhancer. Genes & Dev. 9: 284-293. Sadowski, I., D. Neidbala, K. Wood and M. Ptashne (1991) Gal4 is phosphorylated as a consequence of transcriptional activation. Proc. Natl. Acad. Sci.USA 88: 10510-10514. Ruden, D.M., J. Ma, Y. Li, K. Wood and M. Ptashne (1991) Generating yeast transcriptional activators containing no yeast protein sequences. Nature 350: 250-252. C. Other Support Current NIH-NIGMS Role: PI “Mechanisms of Signal-Induced Alternative Splicing: CD45” Duration: 5/01/08-6/30/12 This project is focused on characterizing the cis-sequences, RNA binding proteins and signaling pathways that mediate signal-induced repression of CD45 exon 4. NIH-NIGMS Role: PI “Coordination of Inducible Alternative Splicing Networks in Human T cells” Duration: 6/01/08-7/31/12 This project is focused on characterizing sequence motifs and trans-regulatory proteins that control coregulation of alternative splicing within multiple genes in response to activation of cultured T cell lines. Completed NSF Role: PI “CAREER: Characterization of novel targets of activation-induced alternative splicing” Duration: 3/1/04-2/28/09 This project is focused on identifying new targets and networks of signal induced splicing regulation in T cells. Welch Foundation Role: PI “Structural Characterization of a Novel Transition in Spliceosome Assembly” Duration: 6/01/06-05/31/09 This is a small foundation award which is funding pilot studies toward a structural characterization of the AEC complex.