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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
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  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, 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 
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 
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 
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 
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 
Protein O-GlcNAcylation and cardiovascular (patho)physiology.
Marsh SA, Collins HE, Chatham JC.
J Biol Chem. 2014 Dec 12;289(50):34449-56 
25336635 
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 
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  
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  
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  
O-GlcNAcylation and cardiovascular disease.
Wright JN, Collins HE, Wende AR, Chatham JC.
Biochem Soc Trans. 2017 Apr 15;45(2):545-553.
 
28408494  
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  
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 
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 
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 
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  
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  
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 
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 
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 
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 
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 
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  

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