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Faculty Detail    
Name JOHN C CHATHAM
  
Campus Address BMR2 512 Zip 2180
Phone  (205) 934-0240
E-mail  jchatham@uabmc.edu
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Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Joint 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  Comprehensive Neuroscience Center  Comprehensive Neuroscience Center Professor
Center  Med - Cardiovascular Disease  Ctr Cardiovasc Bio (Org Ret) Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Professor
Center  Ctr for Free Radical Bio  Ctr for Free Radical Bio Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor
Center  Nephrology Research & Training Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences Research  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
Chatham JC, Young ME, Zhang J. Role of O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins in diabetic cardiovascular complications. Current Opinion in Pharmacology 57: 1-12, 2021 https://doi.org/10.1016/j.coph.2020.08.005  32937226  
Chatham JC, Zhang J, Wende AR. Role of O-linked N-acetylglucosamine (O-GlcNAc) protein modification in cellular (patho)physiology. Physiological Reviews https://doi.org/10.1152/physrev.00043.2019  32730113 
Brahma MK, Pepin ME, Ha C-M, Sun Z, Chatham JC, Habegger KM, Able ED, Paterson AJ, Young ME, Wende AR. Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization. JAHA 2020; 9:e013039 https://doi.org/10.1161/JAHA.119.013039  32750298 
Stewart LT, Abiraman K, Chatham JC, McMahon LL. Increased O-GlcNAcylation rapidly decreases GABAAR currents in hippocampus but depresses neuronal output. Scientific Reports 10, Article number: 7494 (2020) https://doi.org/10.1038/s41598-020-63188-0  32366857 
Bouchard B, Zhu WZ, Chatham JC, Des Rosiers C, Olson A. Glucose Flux through the Hexosamine Biosynthesis Pathway (HBP): First Characterization in an Ex Vivo Mouse Heart. J Biol Chem. 2020 doi: 10.1074/jbc.RA119.010565 PMID:1915250   31915250 
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.    
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 		  
Wright JN, Benavides GA, Johnson MS, Wani W, Ouyang X, Zou L, Collins HE, Zhang J, Darley-Usmar V, Chatham JC. Acute increases in O-GlcNAc indirectly impairs mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover. Am J Physiol Cell Physiol 316: C862-C875, 2019.   30865517 
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  
Temporal partitioning of adaptive responses of the murine heart to fasting.
Brewer RA, Collins HE, Berry RD, Brahma MK, Tirado BA, Peliciari-Garcia RA, Stanley HL, Wende AR, Taegtmeyer H, Rajasekaran NS, Darley-Usmar V, Zhang J, Frank SJ, Chatham JC, Young ME. Life Sci. 2018 Mar 15;197:30-39.
 		 29410090  
Stromal interaction molecule 1 is essential for normal cardiac homeostasis through modulation of ER and mitochondrial function. Collins HE, He L, Zou L, Qu J, Zhou L, Litovsky SH, Yang Q, Young ME, Marchase RB, Chatham JC.
Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):H1231-9. doi: 10.1152/ajpheart.00075.2014. Epub 2014 Feb 28.
 		 24585777 
Blasio MJ, Huynh N, Deo M, Dubrana LE, Walsh J, Willis A, Prakoso D, Kiriazis H, Donner, DG, Chatham JC, Ritchie RH. Defining the progression of diabetic cardiomyopathy in a mouse model of type 1 diabetes Frontiers in Physiology. 2020 Feb 20;11:124. doi: 10.3389/fphys.2020.0012  32153425 
Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus.
Heath JM, Sun Y, Yuan K, Bradley WE, Litovsky S, Dell'Italia LJ, Chatham JC, Wu H, Chen Y.
Circ Res. 2014 Mar 28;114(7):1094-102. doi: 10.1161/CIRCRESAHA.114.302968. Epub 2014 Feb 13. 		 24526702 
O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses.
Taylor EW, Wang K, Nelson AR, Bredemann TM, Fraser KB, Clinton SM, Puckett R, Marchase RB, Chatham JC, McMahon LL.
J Neurosci. 2014 Jan 1;34(1):10-21. doi: 10.1523/JNEUROSCI.4761-12.2014. 		 24381264 
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 
Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.Wright JN, Benavides GA, Johnson MS, Wani W, Ouyang X, Zou L, Collins HE, Zhang J, Darley-Usmar V, Chatham JC. Am J Physiol Cell Physiol. 2019 Jun 1;316(6):C862-C875.   30865517  
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 
Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.=
Peliciari-Garcia RA, Goel M, Aristorenas JA, Shah K, He L, Yang Q, Shalev A, Bailey SM, Prabhu SD, Chatham JC, Gamble KL, Young ME.
Biochim Biophys Acta. 2016 Oct;1861(10):1579-95. doi: 10.1016/j.bbalip.2015.12.012. Epub 2015 Dec 22. 		 26721420  
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 
TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling.
Chen J, Young ME, Chatham JC, Crossman DK, Dell'Italia LJ, Shalev A.
Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H64-75. doi: 10.1152/ajpheart.00151.2016. Epub 2016 May 3. 		 27199118  
Chatham JC, Young ME. Regulation of myocardial metabolism by the cardiomyocyte circadian clock. J Mol Cell Cardiol. 2013 Feb;55:139-46.  22766272 
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 
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  
Temporal partitioning of adaptive responses of the murine heart to fasting.
Brewer RA, Collins HE, Berry RD, Brahma MK, Tirado BA, Peliciari-Garcia RA, Stanley HL, Wende AR, Taegtmeyer H, Rajasekaran NS, Darley-Usmar V, Zhang J, Frank SJ, Chatham JC, Young ME.
Life Sci. 2018 Mar 15;197:30-39.
 		 29410090 
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 
Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus.
Stewart LT, Khan AU, Wang K, Pizarro D, Pati S, Buckingham SC, Olsen ML, Chatham JC, McMahon LL.
J Neurosci. 2017 Aug 23;37(34):8207-8215.


 		 28760863 
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 
Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart.
McGinnis GR, Tang Y, Brewer RA, Brahma MK, Stanley HL, Shanmugam G, Rajasekaran NS, Rowe GC, Frank SJ, Wende AR, Abel ED, Taegtmeyer H, Litovsky S, Darley-Usmar V, Zhang J, Chatham JC, Young ME.
J Mol Cell Cardiol. 2017 Sep;110:80-95.  		 28736261 
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 
O-GlcNAc regulation of autophagy and α-synuclein homeostasis; implications for Parkinson's disease.
Wani WY, Ouyang X, Benavides GA, Redmann M, Cofield SS, Shacka JJ, Chatham JC, Darley-Usmar V, Zhang J.
Mol Brain. 2017 Jul 19;10(1):32.
 		 28724388  
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 
O-GlcNAcylation and cardiovascular disease.
Wright JN, Collins HE, Wende AR, Chatham JC.
Biochem Soc Trans. 2017 Apr 15;45(2):545-553.
 		 28408494  
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 
O-GlcNAcylation and neurodegeneration.
Wani WY, Chatham JC, Darley-Usmar V, McMahon LL, Zhang J.
Brain Res Bull. 2017 Jul;133:80-87. doi: 10.1016/j.brainresbull.2016.08.002. Epub 2016 Aug 4.  		 27497832  
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 
Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.
Peliciari-Garcia RA, Goel M, Aristorenas JA, Shah K, He L, Yang Q, Shalev A, Bailey SM, Prabhu SD, Chatham JC, Gamble KL, Young ME.
Biochim Biophys Acta. 2016 Oct;1861(10):1579-95 		 26721420 
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 
Protein O-GlcNAcylation and cardiovascular (patho)physiology.
Marsh SA, Collins HE, Chatham JC.
J Biol Chem. 2014 Dec 12;289(50):34449-56 		 25336635 
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 
O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long-term depression at hippocampal synapses.
Taylor EW, Wang K, Nelson AR, Bredemann TM, Fraser KB, Clinton SM, Puckett R, Marchase RB, Chatham JC, McMahon LL.
J Neurosci. 2014 Jan 1;34(1):10-21 		 24381264 
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 
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Keywords
Myocardial ischemia, diabetic cardiomyopathy, O-GlcNAc, STIM1, Ca2+-signaling