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Faculty Detail    
Name JOHN C CHATHAM
 
Campus Address BMR2 512 Zip 2180
Phone  (20-5) -240
E-mail  jchatham@uabmc.edu
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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  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Comprehensive Cardiovascular Ctr  Comprehensive Cardiovascular Ctr Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  General Clinical Research Center  Ctr for Free Radical Bio Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor
Center  Medicine  Ctr Cardiovasc Bio (Org Ret) Professor
Center  General Clinical Research Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor

Graduate Biomedical Sciences Affiliations
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.

Society Memberships
Organization Name Position Held Org Link
American Heart Association     
American Physiology Society     
International Society for Heart Research     



Research/Clinical Interest
Title
Cardiomyocyte function and survival in ischemia/reperfusion and the impact of diabetes:
Description
The primary goal of his laboratory is to understand the adverse effects of diabetes on cardiomyocyte function. Over the past 10 years his laboratory have focused on understanding the role of O-linked-N-acetyl-glucosamine (O-GlcNAc) modification of proteins in mediating cardiomyocyte stress responses. We have demonstrated that acute activation of O-GlcNAc levels is remarkably cardioprotective; conversely, in the setting of diabetes where O-GlcNAc levels are chronically elevated cardiomyocytes cell survival pathways such as autophagy are impaired in an O-GlcNAc dependent manner. More recently, his group has been involved in understanding the role of store-operated calcium entry (SOCE) pathways in regulating cardiomyocyte function, which included the generation of a cardiomyocyte-restricted STIM1 KO mouse model. STIM1 plays a central role in regulating SOCE and we demonstrated that a lack of cardiomyocyte STIM1 resulted in metabolic and mitochondrial dysfunction ultimately leading to a dilated cardiomyopathy. These were the first studies to demonstrate that STIM1 is essential for regulating cardiomyocyte homeostasis. For more information about the role of animals in research I recommend the following: http://www.speakingofresearch.com Speaking of Research; http://www.amprogress.org Americans for Medical Progress; http://www.fbresearch.org Foundation for Biomedical Research; http://www.animalresearch.info Animal Research Information.

Selected Publications 
Publication PUBMEDID
Collins HE and Chatham JC. Regulation of cardiac O-GlcNAcylation: More than just nutrient availability
BBA-Molecular Basis of Disease. 2020 https://doi.org/10.1016/j.bbadis.2020.165712 
 
Zhang J, Chatham JC, Young ME. Circadian Regulation of Cardiac Physiology: Rhythms That Keep the Heart Beating. Ann Rev Physiol 82: 5.1-5.23, 2020.    
Biotinylation: a novel posttranslational modification linking cell autonomous circadian clocks with metabolism.
He L, Hamm JA, Reddy A, Sams D, Peliciari-Garcia RA, McGinnis GR, Bailey SM, Chow CW, Rowe GC, Chatham JC, Young ME.
Am J Physiol Heart Circ Physiol. 2016 Jun 1;310(11):H1520-32. doi: 10.1152/ajpheart.00959.2015 
27084392 
Novel role of the ER/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism. Collins HE, Pat BM, Zou L, Litovsky SH, Wende AR, Young ME, Chatham JC. Am J Physiol Heart Circ Physiol. 2019 May 1;316(5):H1014-H1026.   30575437  
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 
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 
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 
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 
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  
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, 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 
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, 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  
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  
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 
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 
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  
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 
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 
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  
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 
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 
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 
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 
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 
Glickson JD, Forder JR, Chatham JC. Imaging of cardiotoxicity. Mol Imaging. 2008 May-Jun;7(3):115-7.   19123981 
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 
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 
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 
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 
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 
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 
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, 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 
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 
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 
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 
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 
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 
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 
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 
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  
Chatham JC, Young ME. Regulation of myocardial metabolism by the cardiomyocyte circadian clock. J Mol Cell Cardiol. 2013 Feb;55:139-46.  22766272 
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 
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 
Chatham JC, Young ME. Metabolic remodeling in the hypertrophic heart: fuel for thought. Circ Res. 2012 Aug 31;111(6):666-8.
 
22935530 
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 
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 
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 

Keywords
Myocardial ischemia, diabetic cardiomyopathy, O-GlcNAc, STIM1, Ca2+-signaling