Mathieu Quesnel-Vallières | Postdoctoral Researcher
BIO
I grew up in Montréal and attended Université de Montréal for my undergrad and Master’s degrees in Microbiology and Immunology. There, I studied HIV genetic diversity and Hepatitis C Virus quasispecies evolution under the guidance of Dr. Hugo Soudeyns at CHU Sainte-Justine. I also visited Dr. Jen-Leih Wu’s lab at Academia Sinica, Taipei, for a few months to develop transgenic zebrafish lines to model HCV pathogenesis. I then completed a PhD with Dr. Benjamin Blencowe and Dr. Sabine Cordes at the Department of Molecular Genetics, University of Toronto, where I investigated the roles of alternative pre-mRNA splicing during mammalian brain development and in autism spectrum disorders.
In 2018, I moved to Philadelphia to join Dr. Kristen Lynch and Dr. Yoseph Barash’s groups as a postdoctoral fellow at the Perelman School of Medicine. My current research focuses on alternative splicing regulation in hematopoietic cells and blood cancers.
Research
I have a long-standing interest for post-transcriptional gene regulation in complex tissues. I am also interested in how loss of gene regulation mechanisms can lead to disease. One such mechanism, alternative splicing, is a powerful way for healthy cells to expand their molecular repertoire during development and maintaining function after differentiation and maturation. After working in the nervous system where neurons use alternative splicing to support network complexity and quickly respond to the environment, I turned to the hematopoietic system where the implications of alternative splicing have not been as clearly defined. I combine computational tools engineered in the Barash lab with the mechanistic expertise of the Lynch lab to survey splicing programs that change during hematopoiesis and address how these programs are regulated. I am currently working to address the following two questions:
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What is the role of alternative splicing during hematopoiesis?
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Is loss of alternative splicing regulation causally involved in blood cancers?
Publications
Gonatopoulos-Pournatzis T, Niibori R, Salter EW, Weatheritt RJ, Tsang B, Farhangmehr S, Liang X, Braunschweig U, Roth J, Zhang S, Henderson T, Sharma E, Quesnel-Vallières M, Permanyer J, Maier S, Georgiou J, Irimia M, Sonenberg N, Forman-Kay JD, Gingras AC, Collingridge GL, Woodin MA, Cordes SP, Blencowe BJ. (2020) Autism-Misregulated eIF4G Microexons Control Synaptic Translation and Higher Order Cognitive Functions. Mol Cell. 77:1176-1192
Fiordaliso SK, Iwata-Otsubo A, Ritter AL, Quesnel-Vallières M, Fujiki K, Nishi E, Hancarova M, Miyake N, Morton JEV, Lee S, Hackmann K, Bando M, Masuda K, Nakato R, Arakawa M, Bhoj E, Li D, Hakonarson H, Takeda R, Harr M, Keena B, Zackai EH, Okamoto N, Mizuno S, Ko JM, Valachova A, Prchalova D, Vlckova M, Pippucci T, Seiler C, Choi M, Matsumoto N, Di Donato N, Barash Y, Sedlacek Z, Shirahige K, Izumi K. (2019) Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment. Am J Hum Genet. 105:987-995.
Quesnel-Vallières M, Weatheritt RJ, Cordes SP, Blencowe BJ. (2019) Autism spectrum disorder: insights into convergent mechanisms from transcriptomics. Nat Rev Genet. 20:51-63.
Tapial J., Ha K.C.H., Sterne-Weiler T., Gohr A., Braunschweig U., Hermoso-Pulido A., Quesnel-Vallières M., Permanyer J., Sodaei R., Marquez Y., Cozzuto L., Wang X., Gómez-Velázquez M., Rayon T., Manzanares M., Ponomarenko J., Blencowe B.J., and Irimia M. (2017) An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms. Genome Res. 27:1759-1768.
Quesnel-Vallières M., Dargaei Z., Irimia M., Gonatopoulos-Pournatzis T., Ip J., Wu M., Sterne-Weiler T., Nakagawa S., Woodin M.A., Blencowe B.J., and Cordes S.P. (2016) Misregulation of an activity-dependent splicing network as a common mechanism underlying autism spectrum disorders. Mol Cell. 64: 1023-1034.
Quesnel-Vallières M., Irimia M., Cordes S.P., and Blencowe B.J. (2015) Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development. Genes Dev. 29:746-759.
Irimia M., Weatheritt R.J., Ellis J., Parikshak N.N., Gonatopoulos-Pournatzis T., Babor M., Quesnel-Vallières M., Tapial J., Raj B., O’Hanlon D., Barrios-Rodiles M., Sternberg M.J., Cordes S.P., Roth F.P., Wrana J.L., Geschwind D.H., and Blencowe B.J. (2014) A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell. 159:1511-1523.
Larouche A., Gaëtan G., El-Bilali N., Quesnel-Vallières M., Martin S.R., Alvarez F., Shoukry N.H., and Soudeyns H. (2012) Seronegative Hepatitis C Virus infection in a child infected via mother-to-child transmission. J Clin Microbiol. 50:2515-2519.
Quesnel-Vallières M., Kouzayha I., Tran E., Barry I., Lasgi C., Mérindol N., Monteil V., Ransy D.G., Boucher M., Lapointe N., and Soudeyns H. (2011) Novel HIV-1 recombinant forms in antenatal cohort, Montreal, Quebec, Canada. Emerg Infect Dis. 17:271-274.
Quesnel-Vallières M., Lemay M., Lapointe N., Martin SR., and Soudeyns H. (2008) HCV quasispecies evolution during treatment with interferon alfa-2b and ribavirin in two children coinfected with HCV and HIV-1. J Clin Virol. 43:236-240.