48165-Pelletier, Stephane

Stephane Pelletier, PhD

Associate Professor of Clinical Medical & Molecular Genetics

IB 252B
Indianapolis, IN
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Dr. Stephane Pelletier holds the position of Associate Professor of Clinical Medical and Molecular Genetics and serves as the Director of the Genome Editing Center (IUGEC) at Indiana University School of Medicine (IUSM). Dr. Pelletier's academic journey is marked by notable achievements. He holds a bachelor's degree in Biochemistry and a master's degree in Pharmacology, both earned from the University of Sherbrooke in Quebec, Canada. He subsequently obtained a Ph.D. degree in Pharmacology from the University of Montreal under the mentorship of Dr. Sylvain Meloche. His pursuit of excellence led him to complete a postdoctoral training in the department of Biochemistry at St. Jude Children's Research Hospital, where he studied signal transduction by cytokine receptors, identified a new family of protein kinases, and gained expertise in genome editing and engineering. Through his subsequent work using mouse genetics, he successfully demonstrated the crucial role of these kinases in maintaining neuronal function and promoting survival. In 2009, Dr. Pelletier's expertise in genome editing brought him to the department of Immunology, where he played a key role in establishing the Embryonic Stem Cell and Genome Editing Facility. As the director of this facility, he was at the forefront of implementing CRISPR technology for mouse genome engineering at St. Jude as early as 2013. Under his supervision, hundreds of mouse models and cell lines were generated, solidifying his reputation as a pioneering leader in the field. In the summer of 2020, Dr. Pelletier moved to Indiana University School of Medicine to establish the Indiana University Genome Editing Center and to pursue his research program on rare pediatric neurodegenerative conditions. With a strong focus on genome editing and rare genetic disorders, Dr. Pelletier's research has been instrumental in advancing our understanding of these complex areas of study. His expertise lies in the application of cutting-edge genome editing technologies to unravel the genetic and molecular basis of rare diseases. Dr. Pelletier's commitment to scientific excellence and his dedication to finding innovative solutions for rare genetic disorders have earned him recognition and admiration among his peers and the scientific community at large. His research continues to bring hope to individuals and families impacted by these challenging conditions.

Key Publications

Cassidy AM, Onal M and Pelletier S*. Novel methods for the generation of genetically engineered animal models. Bone 2022.

Cassidy AM, Thomas DB, Kuliyev E, Chen H and Pelletier S. One-step generation of a conditional allele using a short artificial intron. Heliyon 2022.

Cassidy AM and Pelletier S*. CRISPR-Cas9 mediated insertion of a short artificial intron for the generation of conditional alleles in mice. STAR Protocols 2022.

Cassidy AM and Pelletier S. Emerging CRISPR Technologies. CRISPR Technology 2022.

Determining distinct roles of IL-1α through generation of an IL-1α knockout mouse with no defect in IL-1β expression. Malireddi RK, Bynigeri R, Kancharana B, Sharma BR, Burton AR, Pelletier S, Kanneganti TD. Frontiers in Immunology 7183, 2022.

Rodriguez DA, Quarato G, Liedmann A, Tummers B, Zhang T, Guy C, Crawford JC, Palacios G, Pelletier S, Kalkavan H, Shaw JJP, Fitzgerald P, Chen MJ, Balachandran S, and Green D. Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis. Proc Natl Acad Sci U S A 119 (41) e2207240119. 2022.

Cassidy AM, Kuliyev E, Thomas DB, Chen H, Pelletier S. Engineering allelic series in mice using CRISPR-Cas9 technology. Methods in Enzymology 2022.

Van de Velde LA, Allen EK, Crawford JC, Wilson TL, Guy CS, Russier M, Zeitler L, Bahrami A, Finkelstein D, Pelletier S, Schultz-Cherry S, Thomas PG, Murray PJ. Neuroblastoma formation requires unconventional CD4 T cells and myeloid amino acid metabolism. Cancer Research 2021 10.1158/0008-5472.CAN-21-0691

McNiven V, Gattini D, Siddiqui I, Pelletier S, Brill H, Avitzur Y, Mercimek-Andrews S. SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1. Am J Med Genet A 2021.

Pelletier S, Tummers B, Green DR. Generation of Casp8FL122/123GG mice using CRISPR-Cas9 technology. STAR Protocols 2020 Nov 25;1(3):100181.

Tummers B, Mari L, Guy CS, Heckmann BL, Rodriguez DA, Rühl S, Moretti J, Crawford JC, Fitzgerald P, Kanneganti TD, Janke LJ, Pelletier S, Blander JM, Green DR. Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis. Immunity. 2020 Jun 16;52(6):994-1006.

Samir P, Kesavardhana S, Patmore DM, Gingras S, Malireddi RKS, Karki R, Guy CS, Briard B, Place DE, Bhattacharya A, Sharma BR, Nourse A, King SV, Pitre A, Burton AR, Pelletier S, Gilbertson RJ, Kanneganti TD. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature. 2019 Sep;573(7775):590-594. 

Kuliyev E, Gingras S, Guy CS, Howell S, Vogel P, Pelletier S. Overlapping Role of SCYL1 and SCYL3 in Maintaining Motor Neuron Viability. J Neurosci. 2018 Mar 7;38(10):2615-2630. 

Karki R, Man SM, Malireddi RKS, Kesavardhana S, Zhu Q, Burton AR, Sharma BR, Qi X, Pelletier S, Vogel P, Rosenstiel P, Kanneganti TD. NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer. Nature. 2016 Dec 22;540(7634):583-587. 

Llambi F, Wang YM, Victor B, Yang M, Schneider DM, Gingras S, Parsons MJ, Zheng JH, Brown SA, Pelletier S, Moldoveanu T, Chen T, Green DR. BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation. Cell. 2016 Apr 7;165(2):421-33. 

Pelletier S. SCYL pseudokinases in neuronal function and survival. Neural Regen Res. 2016 Jan;11(1):42-4. 

Gingras S, Earls LR, Howell S, Smeyne RJ, Zakharenko SS, Pelletier S. SCYL2 Protects CA3 Pyramidal Neurons from Excitotoxicity during Functional Maturation of the Mouse Hippocampus. J Neurosci. 2015 Jul 22;35(29):10510-22. 

Pelletier S, Gingras S, Green DR. Mouse genome engineering via CRISPR-Cas9 for study of immune function. Immunity. 2015 Jan 20;42(1):18-27. 

Pelletier S, Gingras S, Howell S, Vogel P, Ihle JN. An early onset progressive motor neuron disorder in Scyl1-deficient mice is associated with mislocalization of TDP-43. J Neurosci. 2012 Nov 21;32(47):16560-73. d

Titles & Appointments

  • Associate Professor of Clinical Medical & Molecular Genetics
  • Director, Indiana University Genome Editing Center
  • Education
    2003 PhD University of Montreal
    1999 MSC University of Sherbrooke
    1996 BSC University of Sherbrooke
  • Research

    Research in Dr. Pelletier’s laboratory focuses on understanding the molecular mechanisms underlying SCYL deficiency syndromes and related, more common, neurodegenerative conditions. SCYL deficiency syndromes are rare genetic disorders caused by inactivating mutations in SCYL genes which include SCYL1, SCYL2 and SCYL3. SCYL1 inactivation in humans causes a multisystem disorder characterized by recurrent episodes of liver failure, growth retardation and range neurological conditions, most notably peripheral neuropathy. Similarly, inactivation of SCYL2 in humans is responsible for a novel syndromic form of arthrogryposis in humans. The phenotype comprises neurogenic arthrogryposis, microcephaly, brain malformation, optic nerve atrophy, limb fractures, profound global developmental delay, and early lethality. Although SCYL3 deficiency has never been reported in humans, studies in mice showed an overlapping role of SCYL1 and SCYL3 in maintaining motor neuron viability. Currently, there are no treatments for these disorders and their prognoses are grim. His laboratory uses a combination of approaches such as cell biology, biochemistry, proteomics, transcriptomics, and mouse genetics to elucidate the molecular functions of SCYL proteins. Our studies not only will shed light on the molecular mechanisms underlying SCYL deficiency syndromes but also on those underlying other neurodegenerative conditions with similar pathological features including Amyotrophic Lateral Sclerosis and Alzheimer’s Disease.

  • Professional Organizations
    American Society for biochemistry and Molecular biolog
    Society for Neuroscience (SfN)

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