The Reilly Group at the University of Pennsylvania is dedicated to translational and genomic studies in human cardio-metabolic disorders. With expertise in preclinical cell and rodent models, human cardio-metabolic disease, as well as human genomics and epidemiology, the group is comprised of wet-lab, computational, and clinical scientists and is integrated across the spectrum of clinical to basic activities and is particularly focused on applying novel technologies in defining the mechanisms of complex cardiovascular disorders.
Currently funded projects include:
- Rodent and human gain-of-function and loss-of-function in modeling genes/pathways in atherosclerosis and insulin resistance, (e.g., metalloproteianses, chemokines)
- Applications of RNA-seq in humans(e.g., tissue- and cell-specific RNA modulation in human inflammation)
- Unbiased glycomics in heart disorders, extensions of GWAS and exome-sequencing in coronary atherosclerosis (e.g., ADAMTS7)
- Epidemiology and clinical trials in humans (e.g., heart disease in kidney disease)
- Novel analytic methods for our high-dimensional data.
Doctor Reilly is also committed to mentoring young scientists in mechanistic translational research in complex human cardiometabolic disorders.
The Reilly group uses human discoveries to identify new mechanisms and treatment targets for heart disease.
The Reilly applies GWAS, DNAseq and RNAseq in searching for new genes and pathways in heart disease.
Using stem cells to study genetic mechanisms in human heart disease: Endothelial cells generated from human induced pluripotent stem cells (hIPSC).
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic Disease
R01-HL-113147 (NIH/NHLBI) (PI: Reilly) 4/16/12 to 3/31/16
Penn Genome Frontiers Institute Pilot Award (PI: Reilly) 7/1/10 to 6/30/13
Translational genomic studies to apply deep RNA sequencing of human tissue and cells to identify novel transcriptomic variations and mechanisms of tissue-specific genetic dysfunction in cardio-metabolic disease.
Translational Studies of ADAMTS7 a Novel GWAS Locus for Coronary Atherosclerosis
ADAMTS7 a is a gene for human atherosclerosis
R01-HL-111694 (NIH/NHLBI) (PI: Reilly) 7/19/12 to 6/30/16
Functional genomics of a locus for human coronary atherosclerosis. Define structure-function of ADAMTS7 interactions with target proteins, assess the effects of loss function and gain of function on mouse atherosclerosis and VSMC function, and interrogate non-synonymous variants discovered upon sequencing of ADAMTS7 in humans for potential loss and gain of function and for association with CAD.
Glycomics of Heart and Lung Disease in the Genomic Era
U01-HL108636 (NIH/NHLBI) (PI: Reilly) 8/20/11 to 6/30/15
Translational studies in human of locus for human myocardial infarction and cardiometabolic traits. Using unbiased mass-spectrometry approaches, we propose to define disease (myocardial infarction and acute lung injury) and cell (platelets and endothelium) specific ABO glycoproteomes in order to develop causal glycopeptides markers of risk and cross-organ, mechanisms-based phenotypes in heart and lung disease.
Unbiased glycomics in discovery of cell specific mechanisms in human heart disease
Fractalkine in Adipose Inflammation and Insulin Resistance
R01-DK-090505 (NIH/NIDDK) (PI: Reilly) 7/19/11 to 5/31/16
Using mice models and human translation, we aim to determine whether fractalkine (CX3CL1-CX3CR1) has independent and/or synergistic actions with CCR2 and CCR5 chemokine pathways in modulating adipose inflammation and its metabolic consequences.
Methods for High-Dimensional Data in Cardiovascular Research
R01-HL107196-06A1 (NIH/NHLBI ) (PI: Foulkes) 2/3/11 to 1/31/16
Other collaborative R01's (e.g., with Mingyao Li PhD)
Develop and apply methods for characterizing the relationship between human genomic data and human complex phenotypes.
Mentored Translational Research in Cardio-metabolic Disease
K24-HL107643 (NIH/NHLBI) (PI: Reilly) 5/13/11 to 4/30/16
To support mechanistic translational and clinical research mentoring, to provide increased time and structure in mentoring young investigators, and to pursue innovative research strategies in training a new generation of leaders in translational research.
- Rachana Shah, MD
- Jane Ferguson, PhD
- Sean O'Neill, PhD, MBA
- Hanrui Zhang, MD, PhD
- Xuan Zhang, PhD
- Robert Bauer, PhD
- Jackie Serfecz, MSc
- Chenyi Xue, MSc
- Liming Qu, MS
- Rhia Shah, BA
- Jian Cui, MD
- Christine Hinkle, MSc
- Jennifer Tabita-Martinez, BSc
- Karen Terembula, BSc
- Raoul Bhatta, MD
- Tramel Parker
- Gayle Meadows
- McGillicuddy FC, de la Llera Moya M, Hinkle CC, Joshi MR, Chiquone EH, Billheimer JT, Rothblat GH, Reilly MP. Inflammation impairs reverse cholesterol transport in vivo. Circulation. 119(8): 1135-45, Mar 2009.
- Zhang Y, McGillicuddy FC, Hinkle CC, O'Neill S, Glick JM, Rothblat GH, Reilly MP. Adipocyte modulation of high-density lipoprotein cholesterol..Circulation. 121(11): 1347-55, Mar 2010.
- Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS; Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies..Lancet.377(9763): 383-92, January 2011.
- *Schunkert H, *König IR, *Kathiresan S, *Reilly MP, *Assimes TL, *Holm H, ..., *O'Donnell CJ, *McPherson R, *Erdmann J, *Samani NJ. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 43(4): 333-8, March 2011. Note: *authors contribted equally.
- Shah R, Christine C. Hinkle C, Ferguson JF, Mehta NN, Li M, Qu L, Lu Y, Putt ME, Ahima RS, Reilly MP. Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes. 1512-8, May 2011.
- Ferguson JF, Hinkle CC, Mehta NN, Bagheri R, DerOhannessian SL, Shah R, Wolfe M, Bradfield JP, Hakonarson H, Wang X, Master S, Rader DJ, Li M, Reilly MP. Translational studies of lipoprotein-associated phospholipase A₂ in inflammation and atherosclerosis. J Am Coll Cardiol.. 59(8): 764-72, Feb 2012.
- CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, ..., Reilly MP, März W, Collins R, Kathiresan S, Hamsten A, Kooner JS, Thorsteinsdottir U, Danesh J, Palmer CN, Roberts R, Watkins H, Schunkert H, Samani NJ. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet.. 2013 Jan;45(1):25-33. 45(1): 25-33, Jan 2013 Notes: doi: 10.1038/ng.2480. Epub 2012 Dec 2.
- Foulkes AS, Matthews GJ, Das U, Ferguson JF, Lin R, Reilly MP. Mixed Modeling of Meta-Analysis P-Values (MixMAP) Suggests Multiple Novel Gene Loci for Low Density Lipoprotein Cholesterol. PLoS One. 28(2): e54812, Feb 2013
- Ferguson JF, Matthews GJ, Townsend RR, Raj DS, Kanetsky PA, Budoff M, Fischer MJ, Rosas SE, Kanthety R, Rahman M, Master SR, Qasim A, Li M, Mehta NN, Shen H, Mitchell BD, O'Connell JR, Alan R Shuldiner AR, Ho WK, Young R, Rasheed A, Danesh J, He J, Kusek JW, Ojo AO, John Flack J, Go AS, Gadegbeku CA, Wright JT, Saleheen D, Feldman HI, Rader DJ, Foulkes AS, Reilly MP; and the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Candidate Gene Association Study of Coronary Artery Calcification in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort Study. J Am Coll Cardiol. 62(9): 789-98, Aug 2013 Notes: August 2013
- Mehta1 NN, Matthews G, Krishnamoorthy P, Shah R, McLaughlin C, Patel P, Budoff M, Chen J, Wolman M, Go A, He J, Kanetsky PA, Master SM, Rader DJ, Raj D, Gadegbeku CA, Shah R, Schreiber M, Fischer MJ, Townsend RR, Kusek J, Feldman HI, Foulkes AS, Reilly MP, and the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: Findings from the Chronic Renal Insufficiency Cohort Study. Eur Heart J. 2013 Dec 19.
- Liu Y, Ferguson JF, Xue C, Ballantyne RL, Silverman IM, Gosai SJ, Serfecz J, Morley MP, Gregory BD, Li M, Reilly MP. Tissue-Specific RNA-Seq in Human Evoked Inflammation Identifies Blood and Adipose LincRNA Signatures of Cardiometabolic Diseases. Arterioscler Thromb Vasc Biol. 2014 Feb 6.
- O'Neill S, Hinkle C, Chen S-J, Sandhu A, Hovhannisyan R, Stephan S, Lagor W, Ahima R, Johnston J, and Reilly MP. Targeting adipose tissue via systemic gene therapy Gene Therapy. (in press) 2014