Description of Research Expertise:
My laboratory uses clinical investigation and applied genomics to reveal mechanisms of human heart failure. This has included establishing a multicenter cohort study of advanced heart failure (Penn Heart Failure Study; PHFS) and a multicenter consortium for human myocardial transcriptomics and eQTL mapping (Myocardial Applied Genomics Network; MAGNet). Notable discoveries include the first demonstration that peripheral blood gene expression provides a clinical biomarker to track cardiac allograft rejection, identification of abnormalities in forkhead signaling and neuregulin signaling in common forms of human heart failure, and discovery of the 1p36 HSPB7/CLCNKA locus as the first bonafide genetic risk factor for non-familial heart failure. In my clinical role I treat patients with advanced heart failure on the inpatient and outpatient heart failure/transplant service.
Selected Publications:
Margulies KB, Hernandez A, Redfield M, Givertz M, Oliveira G, Cole R, Mann D, Whellan D, Kiernan M, Felker GM, McNulty S, Anstrom K, Shah S, Eugene Braunwald E, Cappola TP: Effects of liraglutide on clinical stability in advanced heart failure with reduced ejection fraction: a randomized clinical trial JAMA 316 (5): 500-508,2016.
AbouEzzeddine OF, French B, Mirzoyev SA, Jaffe AS, Levy WC, Fang JC, Sweitzer NK, Cappola TP, Redfield MM: From statistical significance to clinical relevance: A simple algorithm to integrate brain natriuretic peptide and the Seattle Heart Failure Model for risk stratification in heart failure. J Heart Lung Transplant 35 (6): 714-21,2016.
Smith JG, Felix J, Morrison AC, Kalogeropoulos A, Trompet S, Wilk JB, Gidlöf O, Wang X, Morley M, Mendelson M, Joehanes R, Ligthart S, Shan X, Bis JC, Wang YA, Sjögren M, Ngwa J, Brandimarto J, Stott D, Aguilar D, Rice KM, Sesso HD, Demissie S, Buckley BM, Taylor KD, Ford I, Yao C, Liu C, Sotoodehnia N, van der Harst P, Stricker BHC, Kritchevsky SB, Liu Y, Gaziano JM, Hofman A, Moravec CS, Uitterlinden AG, Kellis M, van Meurs JB, Margulies KB, Dehghan A, Levy D, Olde B, Psaty BM, Cupples LA, Jukema J, Djous: Discovery of genetic variation on chromosome 5q22 associated with mortality in heart failure PLoS Genet 12 (5): e1006034,2016.
French B, Wang L, Ky B, Brandimarto J, Basuray A, Fang JC, Sweitzer NK, Cappola TP: Prognostic value of galectin-3 for adverse outcomes in chronic heart failure J Card Fail 22 (4): 256-62,2016.
de Denus S, Rouleau JL, Mann DL, Huggins GL, Cappola TP, Shah S, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dube MP: A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of 3 clinical trials Pharmacogenomics J : 2016.
French B, Saha-Chaudhuri P, Ky B, Cappola TP, Heagerty PJ: Development and evaluation of multi-marker risk scores for clinical prognosis. Stat Methods Med Res 25 (1): 255-271,2016.
Keenan T, Zhao W, Rasheed A, Ho WK, Malik R, Felix JF, Young R, Shah N, Samuel M, Sheikh N, Mucksavage ML, Shah O, Li J, Morley M, Laser A, Mallick NH, Zaman KS, Ishaq M, Rasheed SZ, Memon FU, Ahmed F, Hanif B, Lakhani MS, Fahim M, Ishaq M, Shardha NK, Ahmed N, Mahmood K, Iqbal W, Akhtar S, Raheel R, O'Donnell CJ, Hengstenberg C, März W, Kathiresan S, Samani N, Goel A, Hopewell JC, Chambers J, Cheng YC, Sharma P, Yang Q, Rosand J, Boncoraglio GB, Kazmi SU, Hakonarson H, Köttgen A, Kalogeropoulos A, Frossard: Causal assessment of serum rrate levels in cardiometabolic diseases through a Mendelian randomization study J Am Coll Cardiol 2 (67): 407-16,2016.
Ware JS, Li J, Mazaika E, Yasso CM, DeSouza T, Cappola TP, Tsai EJ, Hilfiker-Kleiner D, Kamiya CA, Mazzarotto F, Cook SA, Halder I, Prasad SK, Pisarcik J, Hanley-Yanez K, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Kealey A, Alexis J, Ramani G, Safirstein J, Boehmer J, Pauly DF, Wittstein IS, Thohan V, Zucker MJ, Liu P, Gorcsan J 3rd, McNamara DM, Seidman CE, Seidman JG, Arany Z: Shared genetic predisposition in peripartum and dilated cardiomyopathies N Engl J Med 374 (3): 233-41,2016.
Perez MV, Pavlovic A, Shang C, Wheeler MT, Miller CL, Liu J, Dewey FE, Pan S, Thanaporn PK, Absher D, Brandimarto J, Salisbury H, Chan K, Mukherjee R, Konadhode RP, Myers RM, Sedehi D, Scammell TE, Quertermous T, Cappola T, Ashley EA: Systems genomics identifies a key role for hypocretin/orexin receptor-2 in human heart failure J Am Coll Cardiol 66 (22): 2522-33,2015.
Das A, Morley M, Moravec CS, Tang WH, Hakonarson H; MAGNet Consortium, Margulies KB, Cappola TP, Jensen S, Hannenhalli S: Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability Nat Commun 6 : 8555,2015.
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