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Faculty Detail    
Name JOHN C CHATHAM
 
Campus Address VH G038 Zip 0019
Phone 205-934-0240
E-mail jchatham@uab.edu
Other websites LinkedIn Profle
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Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Molecular & Cellular Pathology Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Center  Center for Aging  COMPREHENSIVE CTR FOR HEALTHY AGING Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Medicine  Comprehensive Diabetes Ctr Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  General Clinical Research Center  Ctr for Free Radical Bio Professor
Center  Medicine  Ctr Cardiovasc Bio Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
John Charles Chatham was born in Didmarton, Gloucestershire, England in May 1960. He received a B.Sc. (Hons) degree in Chemistry from the University of Southampton England (1983) and a D.Phil. in Biochemistry from University of Oxford (1987). In 1987 he moved to the USA first to a postdoctoral fellowship at Huntington Medical Research Institutes, Pasadena, CA and then to Department of Radiology at Johns Hopkins University School of Medicine. After his postdoctoral training he joined the faculty at Johns Hopkins School of Medicine first as an Instructor and then as an Assistant Professor in the Department of Radiology. He earned the title of Associate Professor of Medicine after coming to UAB in 2000. In 2011 he was appointed as Professor and Director of the Division of Molecular and Cellular Pathology in the Department of Pathology at UAB and Co-Director of the UAB Comprehensive Cardiovascular Center. He served as Chair of the UAB Faculty senate 2011-2012 and was Chair of the Science Policy Committee for the American Physiology Society from 2010-2013. He is currently a member of the Science Policy committee for the Federation of American Societies for Experimental Biology and was recently elected to serve on Council for the American Physiology Society

Society Memberships
Organization Name Position Held Org Link
American Diabetes Association     
American Heart Association     
American Physiology Society  Chair, Science Policy Committee and Councilor    
International Society for Heart Research     

Research/Clinical Interest
Title
Cardiomyocyte function and survival in ischemia/reperfusion and the impact of diabetes:
Description
The overall goal of his laboratory is to understand the impact of alterations in cardiac energy metabolism and substrate utilization on the cardiomyocyte function. We have three major areas of interest: 1) Investigating the mechanisms leading to the increased incidence of heart failure in patients with diabetes and 2) development of new metabolically based therapeutic interventions for the treatment of ischemic heart disease 3) development of metabolic interventions to improve outcomes following trauma and hemorrhage. A common theme to all these projects is the role glucose in post-translational modifications of proteins mediated by the hexosamine biosynthesis pathway leading to protein-O-glycosylation. We propose that this is a central mechanism by which changes in metabolism are transduced into alterations in cellular function. Projects currently underway in our laboratory includes studies involving isolated cardiomyocytes, intact isolated perfused hearts and whole animal models. We use 13C and 1H nuclear magnetic resonance (NMR) spectroscopy to determine metabolic fluxes in the intact heart. In addition, we also use a range of standard physiological, biochemical and molecular techniques. We are also currently exploring proteomic and mass spectrometric methods for the identification and characterization of O-glycosylated proteins.

Selected Publications 
Publication PUBMEDID
Collins HE, Zhu-Mauldin X, Marchase RB, Chatham JC. STIM1/Orai1 mediated SOCE: current perspectives and potential roles in cardiac function and pathology. Am J Physiol Heart Circ Physiol. 2013 Jun 21. [Epub ahead of print]  23792674 
Lauzier B, Vaillant F, Merlen C, Gélinas R, Bouchard B, Rivard ME, Labarthe F, Dolinsky VW, Dyck JR, Allen BG, Chatham JC, Des Rosiers C. Metabolic effects of glutamine on the heart: anaplerosis versus the hexosamine biosynthetic pathway. J Mol Cell Cardiol. 2013 Feb;55:92-100.  23201305 
Zhu-Mauldin X, Marsh SA, Zou L, Marchase RB, Chatham JC. Modification of STIM1 by O-linked N-acetylglucosamine (O-GlcNAc) attenuates store-operated calcium entry in neonatal cardiomyocytes.
J Biol Chem. 2012 Nov 9;287(46):39094-106.  
22992728 
McLarty JL, Marsh SA, Chatham JC. Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart. Life Sci. 2013 Mar 28;92(11):621-7.   22985933 
Chatham JC, Young ME. Metabolic remodeling in the hypertrophic heart: fuel for thought. Circ Res. 2012 Aug 31;111(6):666-8.
 
22935530 
Zou L, Zhu-Mauldin X, Marchase RB, Paterson AJ, Liu J, Yang Q, Chatham JC. Glucose deprivation-induced increase in protein O-GlcNAcylation in cardiomyocytes is calcium-dependent. J Biol Chem. 2012 Oct 5;287(41):34419-31.   22908225 
Hilgers RH, Xing D, Gong K, Chen YF, Chatham JC, Oparil S. Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction. Am J Physiol Heart Circ Physiol. 2012 Sep 1;303(5):H513-22.  22777418 
Chatham JC, Young ME. Regulation of myocardial metabolism by the cardiomyocyte circadian clock. J Mol Cell Cardiol. 2013 Feb;55:139-46.  22766272 
Marsh SA, Powell PC, Dell'italia LJ, Chatham JC. Cardiac O-GlcNAcylation blunts autophagic signaling in the diabetic heart.
Life Sci. 2013 Mar 28;92(11):648-56.  
22728715  
Medford HM, Chatham JC, Marsh SA. Chronic ingestion of a Western diet increases O-linked-β-N-acetylglucosamine (O-GlcNAc) protein modification in the rat heart. Life Sci. 2012 Jun 14;90(23-24):883-8.  22575823 
Chatham JC, Marchase RB. Protein O-GlcNAcylation: A critical regulator of the cellular response to stress. Curr Signal Transduct Ther. 2010 Jan;5(1):49-59.  22308107 
Xing D, Gong K, Feng W, Nozell SE, Chen YF, Chatham JC, Oparil S. O-GlcNAc modification of NFκB p65 inhibits TNF-α-induced inflammatory mediator expression in rat aortic smooth muscle cells. PLoS One. 2011;6(8):e24021.  21904602 
Darley-Usmar VM, Ball LE, Chatham JC. Protein O-linked β-N-acetylglucosamine: a novel effector of cardiomyocyte metabolism and function. J Mol Cell Cardiol. 2012 Mar;52(3):538-49.   21878340 
Dranka BP, Benavides GA, Diers AR, Giordano S, Zelickson BR, Reily C, Zou L, Chatham JC, Hill BG, Zhang J, Landar A, Darley-Usmar VM. Assessing bioenergetic function in response to oxidative stress by metabolic profiling. Free Radic Biol Med. 2011 Nov 1;51(9):1621-35.   21872656 
Laczy B, Fülöp N, Onay-Besikci A, Des Rosiers C, Chatham JC.Acute regulation of cardiac metabolism by the hexosamine biosynthesis pathway and protein O-GlcNAcylation. PLoS One. 2011 Apr 11;6(4):e18417.  21494549 
Des Rosiers C, Labarthe F, Lloyd SG, Chatham JC. Cardiac anaplerosis in health and disease: food for thought. Cardiovasc Res. 2011 May 1;90(2):210-9.   21398307 
Marsh SA, Chatham JC. The paradoxical world of protein O-GlcNAcylation: a novel effector of cardiovascular (dys)function.
Cardiovasc Res. 2011 Feb 15;89(3):487-8. 
21177335 
Laczy B, Marsh SA, Brocks CA, Wittmann I, Chatham JC. Inhibition of O-GlcNAcase in perfused rat hearts by NAG-thiazolines at the time of reperfusion is cardioprotective in an O-GlcNAc-dependent manner. Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1715-27.  20833964 
Marsh SA, Dell'Italia LJ, Chatham JC. Activation of the hexosamine biosynthesis pathway and protein O-GlcNAcylation modulate hypertrophic and cell signaling pathways in cardiomyocytes from diabetic mice. Amino Acids. 2011 Mar;40(3):819-28.   20676904 
Teo CF, Ingale S, Wolfert MA, Elsayed GA, Nöt LG, Chatham JC, Wells L, Boons GJ. Glycopeptide-specific monoclonal antibodies suggest new roles for O-GlcNAc. Nat Chem Biol. 2010 May;6(5):338-43.   20305658 
Nöt LG, Brocks CA, Vámhidy L, Marchase RB, Chatham JC. Increased O-linked beta-N-acetylglucosamine levels on proteins improves survival, reduces inflammation and organ damage 24 hours after trauma-hemorrhage in rats. Crit Care Med. 2010 Feb;38(2):562-71.   20016375 
Hill BG, Dranka BP, Zou L, Chatham JC, Darley-Usmar VM. Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J. 2009 Oct 23;424(1):99-107.   19740075 
Chatham JC, Marchase RB. The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses. Biochim Biophys Acta. 2010 Feb;1800(2):57-66.   19607882 
Degrell P, Cseh J, Mohás M, Molnár GA, Pajor L, Chatham JC, Fülöp N, Wittmann I. Evidence of O-linked N-acetylglucosamine in diabetic nephropathy. Life Sci. 2009 Mar 27;84(13-14):389-93.   19302818 
Glickson JD, Forder JR, Chatham JC. Imaging of cardiotoxicity. Mol Imaging. 2008 May-Jun;7(3):115-7.   19123981 
Zou L, Yang S, Champattanachai V, Hu S, Chaudry IH, Marchase RB, Chatham JC. Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H515-23.   19098112 
Marsh SA, Dell'italia LJ, Chatham JC. Interaction of diet and diabetes on cardiovascular function in rats. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H282-92.   19036853 
Laczy B, Hill BG, Wang K, Paterson AJ, White CR, Xing D, Chen YF, Darley-Usmar V, Oparil S, Chatham JC. Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system. Am J Physiol Heart Circ Physiol. 2009 Jan;296(1):H13-28.  19028792 
Xing D, Feng W, Nöt LG, Miller AP, Zhang Y, Chen YF, Majid-Hassan E, Chatham JC, Oparil S. Increased protein O-GlcNAc modification inhibits inflammatory and neointimal responses to acute endoluminal arterial injury. Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H335-42.   18469144 
Champattanachai V, Marchase RB, Chatham JC. Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2. Am J Physiol Cell Physiol. 2008 Jun;294(6):C1509-20.  18367586 
Fülöp N, Feng W, Xing D, He K, Not LG, Brocks CA, Marchase RB, Miller AP, Chatham JC. Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats. Biogerontology. 2008 Jun;9(3):139-51.   18185980  
Shan D, Marchase RB, Chatham JC. Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes. Am J Physiol Cell Physiol. 2008 Mar;294(3):C833-41.   18184877 
Chatham JC, Nöt LG, Fülöp N, Marchase RB. Hexosamine biosynthesis and protein O-glycosylation: the first line of defense against stress, ischemia, and trauma. Shock. 2008 Apr;29(4):431-40.   17909453 
Liu J, Marchase RB, Chatham JC. Increased O-GlcNAc levels during reperfusion lead to improved functional recovery and reduced calpain proteolysis. Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1391-9.   17573462  
Nöt LG, Marchase RB, Fülöp N, Brocks CA, Chatham JC. Glucosamine administration improves survival rate after severe hemorrhagic shock combined with trauma in rats. Shock. 2007 Sep;28(3):345-52.
 
17545939 
Zou L, Yang S, Hu S, Chaudry IH, Marchase RB, Chatham JC. The protective effects of PUGNAc on cardiac function after trauma-hemorrhage are mediated via increased protein O-GlcNAc levels. Shock. 2007 Apr;27(4):402-8.  17414423 
Marsh SA, Powell PC, Agarwal A, Dell'italia LJ, Chatham JC. Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: the role of hydronephrosis.
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H292-8. Epub 2007 Mar 9. 
17351065  
Fulop N, Zhang Z, Marchase RB, Chatham JC Glucosamine cardioprotection in perfused rat hearts associated with increased O-linked N-acetylglucosamine protein modification and altered p38 activation. Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2227-36.  17208994  
Wang P, Fraser H, Lloyd SG, McVeigh JJ, Belardinelli L, Chatham JC. A comparison between ranolazine and CVT-4325, a novel inhibitor of fatty acid oxidation, on cardiac metabolism and left ventricular function in rat isolated perfused heart during ischemia and reperfusion. J Pharmacol Exp Ther. 2007 Apr;321(1):213-20.  17202401 
Fulop N, Mason MM, Dutta K, Wang P, Davidoff AJ, Marchase RB, Chatham JC. Impact of Type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart. Am J Physiol Cell Physiol. 2007 Apr;292(4):C1370-8.
 
17135297 
Liu J, Marchase RB, Chatham JC Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. J Mol Cell Cardiol. 2007 Jan;42(1):177-85   17069847 
Liu J, Marchase RB, Chatham JC. Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. J Mol Cell Cardiol. 2007 Jan;42(1):177-85.   17069847  
Fulop N, Marchase RB, Chatham JC. Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. Cardiovasc Res. 2007 Jan 15;73(2):288-97.
 
16970929  
Champattanachai V, Marchase RB, Chatham JC. Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein-associated O-GlcNAc. Am J Physiol Cell Physiol. 2007 Jan;292(1):C178-87.   16899550 
Yang S, Zou, L-Y, Bounelis P, Chaudry I, Chatham JC and Marchase RB. Glucosamine administration during resuscitation improves organ function following trauma-hemorrhage. Shock 25: 600-607, 2006.  16721268 
Liu J, Pang Y, Chang T, Bounelis P, Chatham JC and Marchase RB. Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia J. Mol. Cell. Cardiol. 40:303-312, 2006  16337959 
Des Rosiers C and Chatham JC. Myocardial phenotyping using isotopomer analysis of metabolic fluxes. Biochem Soc. Trans. 33: 1413-1417, 2005.  16246133 
Nagy T, Champattanachai V, Marchase RB and Chatham JC. Glucosamine inhibits angiotensin II induced cytoplasmic Ca2+ elevation in neonatal cardiomyocytes via protein-associated O-GlcNAc Am. J. Physiol. - Cell 290: C57-C65, 2006.  16107505 
Wang P, Lloyd SG, and Chatham JC.The impact of high glucose/high insulin and dichloroacetate treatment on carbohydrate oxidation and functional recovery following low flow ischemia and reperfusion in the isolated perfused rat heart. Circulation 111: 2066-2072, 2005  15824201 
Wang P, Lloyd SG, Bonen A and Chatham JC. The impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats during normoxia, ischemia and reperfusion. Am. J. Physiol.-Heart Circ Physiol 288: H2102-H2110, 2005.  15615844 

Keywords
Myocardial ischemia, diabetic cardiomyopathy, O-GlcNAc