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John W. Elrod, PhD

 

Assistant Professor, Pharmacology

Assistant Professor, Center for Translational Medicine

Telephone:  215-707-5480

Fax:  215-707-9890

Email: john.elrod@temple.edu

 

Department of Pharmacology

Center for Translational Medicine

 

Educational Background:

 

BS, Biology (cum laude), Centenary College, Shreveport, LA, 2002

 

PhD, Pathology, Albert Einstein College of Medicine, Bronx, NY, 2007

 

Kirschstein Fellow, Cincinnati Children's Medical Hospital, Howard Hughes Medical Institute, Cincinnati, OH, 2012 - Laboratory of Dr. Jeffrey Molkentin

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professional affiliations:

 

  • Basic Science Council, American Heart Association
  • International Society for Heart Research
  • American Physiological Society

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Research Interests:

 

The Elrod laboratory is focused on two complimentary lines of research--the first being the identification of genetic components of mitochondrial calcium exchange and their role in cellular physiology and heart disease and the second being the utilization of genome-wide functional screening to discover novel modulators of the necrotic cell death program.

 

Heart failure and myocardial infarction, as well as many other diseases, are characterized by significant metabolic dysfunction and cell death, both of which have been shown to initiate and drive disease.  Mitochondrial calcium signaling is a nexus for these processes regulating both oxidative phosphorylation (ATP production) and cell death.  While much is known about how calcium exchange is regulated at the plasma membrane, our understanding of the mitochondrial calcium pool remains elementary.  The lab utilizes in vitro and in vivo techniques including real-time measurements of calcium exchange in isolated cells and genetically engineered mice in clinically relevant disease models to dissect the molecular role of novel genes.

 

Historically, necrotic cell death (characterized by cell swelling, membrane rupture, lysis and inflammation) has largely been thought to be a non-specific-unprogrammed process and thereby void of distinct signaling events and genetic players.  Recently, it has become clear that necrosis, like apoptosis, may be highly regulated and involve specific gene programs.  To discover novel modulators of necrosis, we have utilized genome-wide functional screening in cell-based assay systems (shRNA lentiviral library).  Using a "system biology" approach, we have identified unique players and pathways in cell death and are investigating their mechanisms of action.

 

The ultimate goal of the Elrod lab is to discover new therapeutic avenues for the treatment of disease with a focus towards myocardial infarction and heart failure.

    

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24516168. King AL, Polhemus DJ, Bhushan S, Otsuka H, Kondo K, Nicholson CK, Bradley JM, Islam KN, Calvert JW, Tao YX, Dugas TR, Kelley EE, Elrod JW, Huang PL, Wang R, Lefer DJ, Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. Proc Natl Acad Sci U S A 111:8(3182-7)2014 Feb 25

24430870. Hoffman NE, Chandramoorthy HC, Shanmughapriya S, Zhang XQ, Vallem S, Doonan PJ, Malliankaraman K, Guo S, Rajan S, Elrod JW, Koch WJ, Cheung JY, Madesh M, SLC25A23 augments mitochondrial Ca2+ uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Mol Biol Cell 25:6(936-47)2014 Mar

23991283. Karch J, Kwong JQ, Burr AR, Sargent MA, Elrod JW, Peixoto PM, Martinez-Caballero S, Osinska H, Cheng EH, Robbins J, Kinnally KW, Molkentin JD, Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. Elife 2:(e00772)2013 Aug 27

23538482. Elrod JW, Molkentin JD, Physiologic functions of cyclophilin D and the mitochondrial permeability transition pore. Circ J 77:5(1111-22)2013

22133878. Goonasekera SA, Hammer K, Auger-Messier M, Bodi I, Chen X, Zhang H, Reiken S, Elrod JW, Correll RN, York AJ, Sargent MA, Hofmann F, Moosmang S, Marks AR, Houser SR, Bers DM, Molkentin JD, Decreased cardiac L-type CaČ? channel activity induces hypertrophy and heart failure in mice. J Clin Invest 122:1(280-90)2012 Jan 3

21746915. van Berlo JH, Elrod JW, Aronow BJ, Pu WT, Molkentin JD, Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo. Proc Natl Acad Sci U S A 108:30(12331-6)2011 Jul 26

20890047. Elrod JW, Wong R, Mishra S, Vagnozzi RJ, Sakthievel B, Goonasekera SA, Karch J, Gabel S, Farber J, Force T, Brown JH, Murphy E, Molkentin JD, Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest 120:10(3680-7)2010 Oct

20705924. van Berlo JH, Elrod JW, van den Hoogenhof MM, York AJ, Aronow BJ, Duncan SA, Molkentin JD, The transcription factor GATA-6 regulates pathological cardiac hypertrophy. Circ Res 107:8(1032-40)2010 Oct 15

20566952. Calvert JW, Elston M, Nicholson CK, Gundewar S, Jha S, Elrod JW, Ramachandran A, Lefer DJ, Genetic and pharmacologic hydrogen sulfide therapy attenuates ischemia-induced heart failure in mice. Circulation 122:1(11-9)2010 Jul 6

19704099. Minamishima S, Bougaki M, Sips PY, Yu JD, Minamishima YA, Elrod JW, Lefer DJ, Bloch KD, Ichinose F, Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice. Circulation 120:10(888-96)2009 Sep 8

19608979. Calvert JW, Jha S, Gundewar S, Elrod JW, Ramachandran A, Pattillo CB, Kevil CG, Lefer DJ, Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circ Res 105:4(365-74)2009 Aug 14

19038863. Lorts A, Schwanekamp JA, Elrod JW, Sargent MA, Molkentin JD, Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair. Circ Res 104:1(e1-7)2009 Jan 2

18685092. Elrod JW, Calvert JW, Gundewar S, Bryan NS, Lefer DJ, Nitric oxide promotes distant organ protection: evidence for an endocrine role of nitric oxide. Proc Natl Acad Sci U S A 105:32(11430-5)2008 Aug 12

18316485. Elrod JW, Harrell M, Flagg TP, Gundewar S, Magnuson MA, Nichols CG, Coetzee WA, Lefer DJ, Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury. Circulation 117:11(1405-13)2008 Mar 18

18025468. Bryan NS, Calvert JW, Elrod JW, Gundewar S, Ji SY, Lefer DJ, Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc Natl Acad Sci U S A 104:48(19144-9)2007 Nov 27

17878306. Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, Jiao X, Scalia R, Kiss L, Szabo C, Kimura H, Chow CW, Lefer DJ, Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci U S A 104:39(15560-5)2007 Sep 25

17630348. Gundewar S, Calvert JW, Elrod JW, Lefer DJ, Cytoprotective effects of N,N,N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes. Am J Physiol Heart Circ Physiol 293:4(H2462-71)2007 Oct

16951048. Elrod JW, Greer JJ, Lefer DJ, Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway. Am J Physiol Heart Circ Physiol 292:1(H342-7)2007 Jan

16877550. Duranski MR, Elrod JW, Calvert JW, Bryan NS, Feelisch M, Lefer DJ, Genetic overexpression of eNOS attenuates hepatic ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 291:6(H2980-6)2006 Dec

16844920. Greer JJ, Kakkar AK, Elrod JW, Watson LJ, Jones SP, Lefer DJ, Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure. Am J Physiol Heart Circ Physiol 291:6(H2743-51)2006 Dec

16763164. Elrod JW, Duranski MR, Langston W, Greer JJ, Tao L, Dugas TR, Kevil CG, Champion HC, Lefer DJ, eNOS gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes: a role for eNOS uncoupling. Circ Res 99:1(78-85)2006 Jul 7

16645153. Elrod JW, Greer JJ, Bryan NS, Langston W, Szot JF, Gebregzlabher H, Janssens S, Feelisch M, Lefer DJ, Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 26:7(1517-23)2006 Jul

16189417. Elrod JW, Laroux FS, Houghton J, Carpenter A, Ando T, Jennings MH, Grisham M, Walker N, Alexander JS, DSS-induced colitis is exacerbated in STAT-6 knockout mice. Inflamm Bowel Dis 11:10(883-9)2005 Oct

16081759. Mori M, Stokes KY, Vowinkel T, Watanabe N, Elrod JW, Harris NR, Lefer DJ, Hibi T, Granger DN, Colonic blood flow responses in experimental colitis: time course and underlying mechanisms. Am J Physiol Gastrointest Liver Physiol 289:6(G1024-9)2005 Dec

16034478. Elrod JW, Lefer DJ, The effects of statins on endothelium, inflammation and cardioprotection. Drug News Perspect 18:4(229-36)2005 May

15735432. Ando T, Jordan P, Wang Y, Itoh M, Joh T, Sasaki M, Elrod JW, Carpenter A, Jennings MH, Minagar A, Alexander JS, MAdCAM-1 expression and regulation in murine colonic endothelial cells in vitro. Inflamm Bowel Dis 11:3(258-64)2005 Mar

15694007. Sasaki M, Jordan P, Welbourne T, Minagar A, Joh T, Itoh M, Elrod JW, Alexander JS, Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha. BMC Physiol 5:1(3)2005 Feb 6

15576430. Sharp CD, Houghton J, Elrod JW, Warren A, Jackson TH 4th, Jawahar A, Nanda A, Minagar A, Alexander JS, N-methyl-D-aspartate receptor activation in human cerebral endothelium promotes intracellular oxidant stress. Am J Physiol Heart Circ Physiol 288:4(H1893-9)2005 Apr

15001427. Sasaki M, Elrod JW, Jordan P, Itoh M, Joh T, Minagar A, Alexander JS, CYP450 dietary inhibitors attenuate TNF-alpha-stimulated endothelial molecule expression and leukocyte adhesion. Am J Physiol Cell Physiol 286:4(C931-9)2004 Apr

14766419. Jawahar A, Jawahar LL, Nanda A, Sharp CD, Warren A, Elrod JW, Jennings M, Alexander JS, Minagar A, Stereotactic radiosurgery using the Leksell Gamma Knife: current trends and future directives. Front Biosci 9:(932-8)2004 Jan 1

14680690. Sasaki M, Bharwani S, Jordan P, Elrod JW, Grisham MB, Jackson TH, Lefer DJ, Alexander JS, Increased disease activity in eNOS-deficient mice in experimental colitis. Free Radic Biol Med 35:12(1679-87)2003 Dec 15

12893641. Sharp CD, Hines I, Houghton J, Warren A, Jackson TH 4th, Jawahar A, Nanda A, Elrod JW, Long A, Chi A, Minagar A, Alexander JS, Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor. Am J Physiol Heart Circ Physiol 285:6(H2592-8)2003 Dec

12875904. Oshima T, Blaschuk O, Gour B, Symonds M, Elrod JW, Sasaki M, Jackson TH, Alexander JS, Tight junction peptide antagonists enhance neutrophil trans-endothelial chemotaxis. Life Sci 73:13(1729-40)2003 Aug 15

12850834. Elrod JW, Park JH, Oshima T, Sharp CD, Minagar A, Alexander JS, Expression of junctional proteins in human platelets. Platelets 14:4(247-51)2003 Jun

12823884. Sharp CD, Jawahar A, Warren AC, Elrod JW, Nanda A, Alexander JS, Gamma knife irradiation increases cerebral endothelial expression of intercellular adhesion molecule 1 and E-selectin. Neurosurgery 53:1(154-60; discussion 160-1)2003 Jul

12649355. Sasaki M, Bharwani S, Jordan P, Joh T, Manas K, Warren A, Harada H, Carter P, Elrod JW, Wolcott M, Grisham MB, Alexander JS, The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin reduces disease activity and inflammation in dextran-sulfate induced colitis. J Pharmacol Exp Ther 305:1(78-85)2003 Apr

12388057. Sasaki M, Ostanin D, Elrod JW, Oshima T, Jordan P, Itoh M, Joh T, Minagar A, Alexander JS, TNF-alpha -induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent. Am J Physiol Cell Physiol 284:2(C422-8)2003 Feb

12184633. Blaschuk OW, Oshima T, Gour BJ, Symonds JM, Park JH, Kevil CG, Trocha SD, Michaud S, Okayama N, Elrod JW, Alexander JS, Sasaki M, Identification of an occludin cell adhesion recognition sequence. Inflammation 26:4(193-8)2002 Aug

12162724. Alexander JS, Elrod JW, Extracellular matrix, junctional integrity and matrix metalloproteinase interactions in endothelial permeability regulation. J Anat 200:6(561-74)2002 Jun

11781812. Alexander JS, Zhu Y, Elrod JW, Alexander B, Coe L, Kalogeris TJ, Fuseler J, Reciprocal regulation of endothelial substrate adhesion and barrier function. Microcirculation 8:6(389-401)2001 Dec

11498780. Alexander JS, Elrod JW, Park JH, Roles of leukocyte and immune cell junctional proteins. Microcirculation 8:3(169-79)2001 Jun

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