Kristen W. Lynch, PhD

faculty photo
Benjamin Rush Professor of Biochemistry
Department: Biochemistry and Biophysics

Contact information
Department of Biochemistry and Biophysics, Stellar-Chance Labs 909B
422 Curie Blvd
Philadelphia, PA 19104-6059
Office: 215-573-7749
Fax: 215-573-8899
Harvard University, 1990.
Harvard University, 1996.
Permanent link
> Perelman School of Medicine   > Faculty   > Details

Description of Research Expertise

RESEARCH INTERESTS: mechanisms and consequences of alternative RNA processing in human immune response

KEY WORDS: RNA binding proteins, alternative splicing, alternative polyadenylation, gene regulation, host-viral interaction, cancer

Recent insight into the human genome has revealed that most genes encode multiple distinct protein isoforms through the process of alternative pre-mRNA splicing and alternative polyadenylation. My laboratory focuses on understanding the biochemical mechanisms and regulatory networks that control such RNA processing events the human immune system. We have identified multiple kinase pathways and post-transcriptional mechanisms by which the abundance and activity of RBPs are regulated in a signal-dependent manner. The lab was also one of the first to demonstrate regulation of splicing following initial recognition of splice sites; thereby expanding potential vulnerabilities for therapeutic regulation of splicing. In addition, we have identified broad programs of alternative splicing induced by antigen stimulation of T cells and by viral infection and demonstrated how these changes in gene expression control the functional response of the immune system. This work highlights the potential for treatment of infection and autoimmunity through regulation of splicing of specific genes. With regards to cancer, the Lynch lab has worked with collaborators to reveal that dysregulated splicing often phenocopies genetic mutations in leukemia. Current studies are expanding our analysis to study other mechanisms of RNA regulation, including alternative polyadenylation, translation and mRNA decay, with focus on the coordination of these processes with one another through RBPs.

Many rotation projects are available.

Selected Publications

Wang D, Quesnel-Vallieres M, Jewell S, Elzubeir M, Lynch K, Thomas-Tikhonenko A, Barash Y.: A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers. Nat Commun 14: 63, Jan 2023.

Burke JM, Ripin N, Ferretti MB, St Clair LA, Worden-Sapper ER, Salgado F, Sawyer SL, Perera R, Lynch KW, Parker R.: RNase L activation in the cytoplasm induces aberrant processing of mRNAs in the nucleus. PLoS Pathog 18: e1010930, Nov 2022.

Blake D, Radens CM, Ferretti MB, Gazzara MR, Lynch KW.: Alternative splicing of apoptosis genes promotes human T cell survival. Elife 11: e80953, Oct 2022.

Basavappa MG, Ferretti M, Dittmar M, Stoute J, Sullivan MC, Whig K, Shen H, Liu KF, Schultz DC, Beiting DP, Lynch KW, Henao-Mejia J, Cherry S.: The lncRNA ALPHA specifically targets chikungunya virus to control infection. Mol Cell 82: 3729-3744, Oct 2022.

Peart NJ, Hwang JY, Quesnel-Vallières M, Sears MJ, Yang Y, Stoilov P, Barash Y, Park JW, Lynch KW, Carstens RP.: The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function. iScience 25: 105205, Sep 2022.

Gao S, Esparza M, Dehghan I, Aksenova V, Zhang K, Batten K, Ferretti MB, Begg BE, Cagatay T, Shay JW, García-Sastre A, Goldsmith EJ, Chen ZJ, Dasso M, Lynch KW, Cobb MH, Fontoura BMA.: Nuclear speckle integrity and function require TAO2 kinase. Proc Natl Acad Sci U S A 119: e2206046119, Jun 2022.

Jha A, Quesnel-Vallières M, Wang D, Thomas-Tikhonenko A, Lynch KW, Barash Y.: Identifying common transcriptome signatures of cancer by interpreting deep learning models. Genome Biol 23: 117, May 2022.

Zheng S, Gillespie E, Naqvi AS, Hayer KE, Ang Z, Torres-Diz M, Quesnel-Vallières M, Hottman DA, Bagashev A, Chukinas J, Schmidt C, Asnani M, Shraim R, Taylor DM, Rheingold SR, O'Brien MM, Singh N, Lynch KW, Ruella M, Barash Y, Tasian SK, Thomas-Tikhonenko A.: Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies. Blood Cancer Discov 3: 103-115, Mar 2022.

Sengupta S, West KO, Sanghvi S, Laliotis G, Agosto LM, Lynch KW, Tsichlis PN, Singh H, Patrick KL, Guerau-de-Arellano M.: PRMT5 Promotes Symmetric Dimethylation of RNA Processing Proteins and Modulates Activated T Cell Alternative Splicing and Ca(2+)/NFAT Signaling. Immunohorizons 5: 884-897, Oct 2021.

Slaff B, Radens CM, Jewell P, Jha A, Lahens NF, Grant GR, Thomas-Tikhonenko A, Lynch KW, Barash Y.: MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis. Nat Commun 12: 3353, Jun 2021.

back to top
Last updated: 01/26/2023
The Trustees of the University of Pennsylvania