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. Simon Gregory is a Professor in the Departments of Neurology, Medicine, and Molecular Genetics and Microbiology, and the Director of Genomics and Epigenetics at the Duke Molecular Physiology Institute. Dr. Gregory's research applies the experience he gained from leading the mapping of the mouse genome and the sequencing of human chromosome 1 for the Human Genome Project to elucidating the molecular mechanisms underlying multi-factorial diseases. His primary areas of research involve the identification of the genetic, genomic, and epigenetic factors that contribute to the development of chronic complex disease. These include the characterization of molecular factors influencing the development and progression of multiple sclerosis in human and animal models, and the generation of genetic, transcriptome and epigenetic predictors of oxytocin response in human cohorts and animal models of autism.  His research also includes developing and applying novel single cell technologies towards understanding the mechanisms of disease development within the Molecular Genomics Core at the DMPI . Dr. Gregory is the Research Director of the Duke Center of Autoimmunity and MS in the Department of Neurology, and Scientific and Academic Advisor at the David H Murdock Research Institute.

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 to be associated with the disease (1). The finding forms the basis of ongoing functional research to identify the mechanism by which the cytokine receptor (IL7R) is implicated in the development of the disease. Dr. Gregory's lab is collaborating with Dr. Mariano Garcia Blanco (UTMB) to identify additional genes that regulate IL7R splicing that are themselves associated with MS but which may also play a broader role in the development of autoimmune disease (2). Dr. Gregory is Principal Investigator of the MS-MURDOCK 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 (3), and a 26-instrument quality of life questionnaire. Dr. Gregory has also developed a longitudinal cohort of primary progressive MS patients to develop disease trajectories using ultra-sensitive protein detection platforms. Finally, Dr. Gregory is exploring the efficacy of novel MS drugs including hydroxyl-cholesterols with Drs. Eric Benner (Duke, Pediatrics) and Mari Shinohara (Duke, Immunology), and statins with the Immune Tolerance Network.

Autism:
Recent CDC estimates suggest that autism affects more than one in 68 children in the US. The Gregory lab is using independent approaches to not only understand the genetic and epigenetic mechanisms underlying autism, but also how children can be treated to resolve their symptoms. Dr. Gregory is project PI in the SOARS-B consortium headed by Dr. Lin Sikich of Duke University's Center for Autism and Brain Development. This exciting new clinical trial is assessing the efficacy of nasally delivered oxytocin to ameliorate some of the core deficits of autism. The Gregory lab's role in the consortium is to develop genetic and epigenetic predictors of oxytocin response and to assess the long term effects of drug exposure on these modalities (4). In collaboration with Drs. Sheryl Moy (UNC, Psychiatry) and Dr. Yong-hui Jiang (Duke, Pediatrics), Dr. Gregory's lab has recently been awarded an NIH grant to explore the mechanisms of oxytocin response in an animal model of the disease, to extend the epigenetic profiling of SOAR-B responders, and to refine the epigenetic regulation of the oxytocin receptor (OXTR). The findings of this grant will provide valuable data for the mode of action of oxytocin response in specific regions of the brain that will applicable to clinical trials of oxytocin response in numerous psychosocial phenotypes, including autism. Finally, together with Professor Emeritus of Pediatrics Dr. G. Robert Delong, Dr. Gregory is investigating how epigenetic factors within a multigenerational family can lead to the development of the disorder and how the identification of compound genetic risk factors in psychosocial families by exome sequencing may lead to the development of autism.

Cardiovascular Disease:
It is estimated that every one in four deaths in the US is attributable to heart disease and the health burden is believed to be greater than $100 billion annually. Dr. Gregory is collaborating with Drs. Svati Shah, Bill Kraus, and Elizabeth Hauser to identify the genetic architecture of the disease using Duke's unique CATHGEN cohort via GWAS and candidate gene association studies, metabolomic profiling with Dr. Chris Newgard, and transcriptomic and epigenomic approaches (5,6,7) . The latter, profiling the methylome of cardiovascular disease, also forms the basis of collaboration with cardiologists Drs. Svati Shah, Asad Shah, and G. Chad Hughes to identify DNA methylation and gene expression differences during bi- and tricuspid aorta development. 

 

 

Administrators

Erin Rhodes

Staff

Karen Abramson

Stephanie Arvai

Elizabeth Burns

Stephanie Giamberardino

Santosh Gupta, PhD

Emily Hocke

Vaibhav Jain

Julie Rochelle

Graduate/Medical Students

James Giarraputo

Stephen Siecinski

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)

Former Trainees
Mollie Minear PhD - UPGG Graduate Program (Fellow - NIH, National heart, Lung, and Blood Institute)
Christina Markunas PhD - UPGG Graduate Program (RTI - Epigenetic Epidemiologist)
Jessica Connelly PhD - Post Doctoral Fellow (University of Virginia - Faculty)
Beth Sutton PhD - Post Doctoral Fellow (Campbell University - Faculty)
Jama Purser MD - Clinical Fellow

Current and Past Undergraduate Trainees
Sofia Velasquez – Colgate University
Nicole Joy - Duke University
Lauren Vaughan - Duke University
Angeline Luong - Duke University
Hunter Nisonoff - Duke University
Thomas Boyle - Duke University
Allison Dorogi - Duke University
Jaret (Mac) Karnuta - Duke University
Charles Zhao – Duke University
Nava Barman - Duke University
Cynthia Rouf – North Carolina State University
William Morgenlander – Notre Dame
Aisha Venugopal - UNC, Chapel Hill
Seth Newman - Washington University

Current and Past High School Trainees
Maya Watson – Durham Academy
Grace Mott – Durham School of the Arts
Kaitlyne Sheehan – Durham School of the Arts
Maya Montani - Durham School of the Arts
Reuben Tacas – Durham School of the Arts
Sam Finlay – Durham School of the Arts
Drew Harrelson – North Carolina School of Science and Math
Hailey Gosnell – North Carolina School of Science and Math
Anna Scotton – North Carolina School of Science and Math
Jamie Chamberlin – North Carolina School of Science and Math