Simon Gregory, PhD

Director of Genomics and Epigenetics
Duke Molecular Physiology Institute

Position

Professor in Neurology, Medicine, and Molecular Genetics and Microbiology

Contact

Carmichael Building

919 684 0726

simon.gregory@duke.edu

Summary

Dr. Gregory is a tenured Professor and Vice Chair of Research in the Department of Neurology at Duke University and Director of the Molecular Genomics Core at the Duke Molecular Physiology Institute (DMPI). As a neurogenomicist, Dr. Gregory applies the experience gained from leading the sequencing of chromosome 1 for the Human Genome Project to elucidating the mechanisms underlying multi-factorial diseases using genetic, genomic, and epigenetic approaches. Dr. Gregory’s primary areas of research involve understanding the molecular processes associated with disease development and drug induced remyelination in multiple sclerosis, and identifying predictors of plasma oxytocin response on social behavior in human cohorts and animal models of autism. He is also leading the development and application of novel single cell and spatial molecular technologies at Duke towards understanding the pathogenic mechanisms of neurodegenerative disease and brain tumors. Dr. Gregory is also the Director of Genomics and Epigenetics at the DMPI and Director of the Duke Center of Autoimmunity and MS in the Department of Neurology.

BSc, Royal Melbourne Institute of Technology, Melbourne, Australia
PhD, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

The Gregory lab is involved in several lab-based and collaborative research projects that focus on identifying the genomic, genetic, and epigenetic underpinnings of complex disease.

Multiple Sclerosis:

In 2007 Dr Gregory and his collaborators identified the first MS gene outside of the MHC (interleukin 7 receptor, IL7R) to be associated with the disease (Gregory et al, 2007 Nature Genetics). A continuing collaboration with Dr. Mariano Garcia Blanco (UTMB) has subsequently shown that the DExD-Box Helicase 39B gene (DDX39B) not only regulates alternative splicing of IL7R but it is also genetically associated with MS in a rarely proven epistatic interaction (Galarza-Muñoz et al, 2017, Cell). Most recently, Drs. Gregory and Garcia-Blanco have further established the novel splicing mechanisms of IL7R around the evolutionary conservation of polypyrimidine tracts in IL7R that influence U2AF2 binding and U2 snRNP recruitment to IL7R exon 6 that harbors MS associated C allele (Schott et al, 2021, RNA).

Dr. Gregory is Principal Investigator of the MURDOCK_MS study that developed a ~1,000 patient multiple sclerosis collection that has been used to identify multi-omic biomarkers to facilitate reclassification of the disease (Cote et al 2019, Multiple Sclerosis and Related Disorders), and the use of ultra-high sensitivity protein assays to plot the trajectory of disease development in a cohort of primary progressive MS patients (under review Giarraputo et al, Journal of Neuroimmunology).

Dr. Gregory is also exploring the efficacy of a novel hydroxyl-cholesterol (HC) treatment of remyelination in MS with Drs. Mari Shinohara (Duke, Immunology), and Glenn Matsushima (UNC-CH, Microbiology and Immunology). In this transformative study, Dr. Gregory and his colleagues are trying to understand the cellular mechanisms in which HCs trigger the differentiation of neural progenitor cells into oligodendrocyte progenitor cells (OPCs) and/or OPCs into oligodendrocytes, the cell that is critical for triggering remyelination in MS. Early data provides exciting evidence of remyelination in the context of a demyelinating pre-clinical model of MS.

 

Autism:

Recent CDC estimates suggest that autism affects more than one in 68 children in the US. The Gregory lab is using genetic and epigenetic approaches to understand the mechanisms driving core deficits associated with autism at developmental and therapeutic levels via oxytocin treatment in pre-clinical and human trials with Dr. Lin Sikich. In collaboration with Dr. Sheryl Moy (UNC, Psychiatry) and Dr. Yong-hui Jiang (Yale, Medical genetics), Dr. Gregory's lab is exploring the mechanisms of oxytocin response in a clinical trial of autistic children, to refine the epigenetic regulation of the oxytocin receptor (OXTR), and to understand the molecular underpinnings of oxytocin effects and societal interaction in an animal model of autism. The findings will provide valuable insight into the mode of action of oxytocin response in specific regions of the brain that will be applicable to clinical trials of oxytocin treatment in numerous psychosocial phenotypes, including autism.

 

Development:

Dr. Gregory’s lab is also pioneering the development of single cell ‘omic profiling and spatial transcriptomic and in situ sequencing approaches towards understanding the mechanism of disease development and progression. Through collaborative research and as Director of the Molecular Genomics Core, Dr. Gregory has facilitated research of more than 60 single cell and spatial projects at Duke, including his own studies into oxytocin response in preclinical models of autism (above), HC treatment response in neural stem cells (above), the progression of Alzheimer’s disease with Drs. Jerry Wang and Dianne Cruz , and in the development of brain tumors with Dr. David Ashley in Duke’s Brain Tumor Center.

Administrators

Erin Rhodes

Staff

Karen Abramson

Stephanie Arvai

Qunsheng Dai

Stephanie Giamberardino

Emily Hocke

Vaibhav Jain

Julie Rochelle

Kevin Stevenson

Postdocs / Fellows

Stephen Siecinski, PhD

Graduate/Medical Students

Miko Liu

The Gregory lab is recruiting graduate students primarily through these programs:

Former Lab Members
Rachel Cote PhD  - UNC Chapel Hill
Christina Sheedy PhD  - Duke UPGG Program
Matthew Schemmel  - Illumia
Josh Virgadamo  - U.S. Navy
Jennifer Doss  - Duke UPGG Program
Shera Watson  - Duke Cardiology
Aaron Towers  - Duke UPGG Program
Jason Gibson  - Caribou Biosciences

Former Trainees
Mollie Minear PhD - UPGG Graduate Program (Program Officer - NIH, NHLBI)
Christina Markunas PhD - UPGG Graduate Program (Triangle Insights Group, LLC)
Deidre Krupp PhD - Science Writer
Jessica Connelly PhD - Post Doctoral Fellow (University of Virginia - Faculty)
Beth Sutton PhD - Post Doctoral Fellow (Campbell University - Faculty)
Jama Purser MD - Clinical Fellow, Duke University
Nazema Siddiqui MD - Junior Faculty, Urogynecology, Duke University
Chad Grotegut MD - Junior Faculty, Chief of MFM and Vice Chair of Obstetrics at Wake Forest Baptist Medical Center
Audrey Dickey Junior Faculty, Department of Neurology, Duke University

Current and Past Undergraduate Trainees
Matthew Schemmel - Duke University
Cynthia Rouf - North Carolina State University
Lauren Vaughan - Duke University
Angeline Luong - Duke University
Hunter Nisonoff - Duke University
Seth Newman - Washington University
Allison Dorogi - Duke University
Aisha Venugopal - UNC-Chapel Hill
Thomas Boyle - Duke University
Charles Zhao - Duke University
William Morgenlander - Notre Dame
Sofia Velazquez - Colgate University
Navajyoti Barman - Duke University
Molly Monsour - Duke University
Eduardo Chavez - Duke University

Current and Past High School Trainees
Hailey Gosnell – North Carolina School of Science and Math
Drew Harrelson – North Carolina School of Science and Math
Elijah Rogan-Kelly - Durham School of the Arts
Grace Mott – Durham School of the Arts
Anna Scotton – North Carolina School of Science and Math
Kaitlyne Sheehan – Durham School of the Arts
Maya Watson – Durham Academy
Jamie Chamberlin – North Carolina School of Science and Math
Reuben Tacas - Durham School of the Arts
Samuel Finlay - Durham School of the Arts
Maya Montani - Durham School of the Arts
Ethan Barber - Durham School of the Arts
Ben Kearsley - Durham School of the Arts
Deva Holliman - Durham School of the Arts
Hannah Weinbaum - Durham School of the Arts