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.
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.
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.
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.