Jessica J. Connelly

Education

  • BS, Richard Stockton College of New Jersey
  • PhD, State University of New York at Stony Brook
  • Postdoc, Duke University

Primary Appointment

  • Assistant Professor, Medicine- Cardiovascular Medicine

Contact

Research Interest(s)

Epigenetic mechanisms involved in complex human disease

Research Description



Epigenetic mechanisms involved in complex human disease
As our understanding of the intricate mechanisms of gene regulation grows, it is apparent that (1) traditional methods of identifying aberrant genetic mechanisms associated with complex disease, such as linkage and association studies, will not be sufficient and (2) the paradigm where variants that lead to disease must exist within the coding region of a gene needs to be changed. One step towards better modeling of disease risk and understanding disease variants lies in expanding the paradigm of complex disease study to include epigenetic influences that contribute to disease. Methylation of CpG sites within DNA serves as one type of epigenetic cue which results in changes in gene function. The identification of methylated regions in the context of the human genome will define a relationship between the regulation/misregulation of epigenetic modifications and disease.

Current Projects

Cardiovascular Related
(1) To create comprehensive maps of the cytosine methylated genome in: 
    • human cardiovascular endothelial cells (diseased/non-diseased states) *
    • human cardiovascular smooth muscle cells (diseased/non-diseased states)

(2) Assess regions that change methylation state with disease in:
    • peripheral blood cells from coronary artery disease patients and controls *
    • peripheral blood cells from patients with increased blood homocysteine levels *
    • diseased and non-diseased human aorta *

(3) To map DNA methylation pattern changes caused by induction of hyperhomocysteinemia in vitro in endothelial cells.

(4) To determine the impact of aberrant methylation on endothelial cell and smooth muscle cell phenotype.

Neurobiology Related
(5) To define the effect of bisphenol A on the epigenome in the developing mouse brain and to relate these changes to mouse behavior and human neurodevelopmental disorders. (collaboration with Dr. Emilie Rissman)

(6) To epigenetically characterize candidate genes that may be altered by androgen exposure during pregnancy; we hope to identify new targets for treatment of individuals with infertility and metabolic dysfunction that can result from this exposure. (collaboration with Dr. Sue Moenter)

(7) To quantify epigenetic modulation of genes and demonstrate how this modulation affects human social behavior. We will use regional brain activation evoked by well-validated social tasks as an index of social function. *
(collaboration with Dr. James Morris) *projects available

Selected Publications

  • Jack A, Connelly J, Morris J. DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Frontiers in human neuroscience. 2012;6 280. PMID: 23087634 | PMCID: PMC3467966
  • Wolstenholme J, Edwards M, Shetty S, Gatewood J, Taylor J, Rissman E, Connelly J. Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology. 2012;153(8): 3828-38. PMID: 22707478 | PMCID: PMC3404345
  • Kfoury A, Snow G, Budge D, Alharethi R, Stehlik J, Everitt M, Miller D, Drakos S, Reid B, Revelo M, Gilbert E, Selzman C, Bader F, Connelly J, Hammond M. A longitudinal study of the course of asymptomatic antibody-mediated rejection in heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2011;31(1): 46-51. PMID: 22153551
  • Minear M, Crosslin D, Sutton B, Connelly J, Nelson S, Gadson-Watson S, Wang T, Seo D, Vance J, Sketch M, Haynes C, Goldschmidt-Clermont P, Shah S, Kraus W, Hauser E, Gregory S. Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease. Human genetics. 2011;129(6): 641-54. PMID: 21298289 | PMCID: NIHMS335416
  • Wolstenholme J, Taylor J, Shetty S, Edwards M, Connelly J, Rissman E. Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice. PloS one. 2011;6(9): e25448. PMID: 21980460 | PMCID: PMC3182223
  • Wolstenholme J, Rissman E, Connelly J. The role of Bisphenol A in shaping the brain, epigenome and behavior. Hormones and behavior. 2010;59(3): 296-305. PMID: 21029734