Simon Gregory, PhD

Director of Genomics and Epigenetics
Duke Molecular Physiology Institute


Professor in Neurology, Medicine, and Molecular Genetics and Microbiology


Carmichael Building

919 684 0726


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 underlie 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; the generation of genetic, transcriptome and epigenetic predictors of oxytocin response in human cohorts and animal models of autism; and the identification of the complex genetic and epigenetic factors that give rise to the development of cardiovascular disease. His research also includes developing and applying single cell technologies towards understanding the mechanisms of disease development within the Molecular Genomics Core at the DMPI . Dr. Gregory is the Director of Graduate Studies for the Duke University Program in Genetics and Genomics, 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) and ILR are implicated in the disease. Dr. Gregory's lab is assessing T cell signaling of IL7 in MS patients, understanding the mechanism of IL7R splicing (2), and construction of an IL7R mouse model of the disease in collaboration with Dr. Mariano Garcia Blanco (UTMB). Dr. Gregory is Principal Investigator of the MS-MURDOCK study. The study has developed a ~1,000 patient multiple sclerosis collection that is independent of subtype with the aims of understanding the mechanisms associated with MS development and progression, and the generation of multi-omic biomarkers to facilitate reclassification of the disease. Finally, Dr. Gregory is using a mouse model of MS experimental autoimmune encephalomyelitis (EAE), to understand the molecular mechanisms of disease development and efficacy of novel drugs. The Gregory lab is exploring the dynamics of mRNA and miRNA expression during EAE course using next generation sequencing approaches to elucidate the changes and interrelationships of gene function during EAE development and recovery. These data will provide the baseline for evaluating the mechanism of novel cyclotide drug function in collaboration with Dr. Christian Gruber (University of Brisbane). (3), and hydroxyl-oxysterols with Drs. Eric Benner (Duke, Pediatrics) and Mari Shinohara (Duke, Immunology).

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. 

Developmental Projects:
The Gregory lab is involved in a number of high risk high reward projects to identify the modalities of disease development. In collaboration with Dr. Chris Newgard, the Gregory lab is profiling gene expression changes in pancreatic islets under the regulation of Pdx and Nkx in a rat model of diabetes using next generation RNA-, ChIP-Seq and single cell expression profile approaches; while a collaboration with Drs. Fashid Guilak (Washington University) and Dianne Little (Purdue University) is aimed at identifying the epigenetic mechanisms associated with diet induced changes of mouse stem cells in the development of obesity and OA.



Erin Rhodes


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