48165-Pelletier, Stephane

Stephane Pelletier, MSC, PhD

Associate Professor of Clinical Medical & Molecular Genetics

IB 252B
Indianapolis, IN


Dr. Pelletier joined Indiana University School of Medicine in the summer of 2020 to establish the Indiana University Genome Editing Center, a core facility whose mission is to provide investigators access to genome editing technologies, and to continue his research program on SCYL-deficiency syndromes and related neurodegenerative conditions, and the development and implementation of new genome engineering approaches. Dr. Pelletier holds a bachelor’s degree in Biochemistry and a master’s degree in Pharmacology from the University of Sherbrooke, and a Ph.D. degree in Pharmacology from the University of Montreal. He also completed a postdoctoral training in the department of Biochemistry at St. Jude Children’s Research Hospital before joining the Department of Immunology to establish the Embryonic Stem Cell and Genome Editing Facility in 2009. As director of this facility, Dr. Pelletier has pioneered the implementation of CRISPR technology for mouse genome engineering at St. Jude back in 2013 and supervised the generation of hundreds of mouse models and cell lines, establishing himself as a leader in the field.

Key Publications

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.

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