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Mouton Biosketch

OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 01/31/2026)

BIOGRAPHICAL SKETCH

NAME: Alan Mouton

eRA COMMONS USER NAME (credential, e.g., agency login): Riktora

POSITION TITLE: Instructor

EDUCATION/TRAINING

Personal Statement

My research interests are focused on understanding the pathogenesis of cardiovascular disease. My long-term career goal is to better identify the roles of and mechanisms by which fibroblasts contribute to cardiac injury and impair appropriate cardiac remodeling, so as to identify preventative measures and potential therapies. My doctoral work focused on mechanisms of chronic alcohol-induced cardiac remodeling, particularly with regards to the extracellular matrix and fibroblast activity. I have expertise in several rodent models of heart failure, including coronary artery ligation to induce permanent myocardial infarction, induction of hypertension by angiotensin II infusion, suprarenal abdominal and transverse aortic constriction, as well as in vivo measurements of cardiac function (echocardiography, pressure-volume loop assessments). I also have experience in several ex vivo and biochemical assays, including cardiac and bone marrow macrophage culture, flow cytometry, extracellular metabolic flux analysis by Seahorse, RNA-sequencing, real-time PCR, immunohistochemistry, and Western blotting. Since joining the University of Mississippi Medical Center (UMMC) in 2017, I have been highly productive in the excellent scientific environment at the institution, having published 33 manuscripts and receiving a highly competitive American Heart Association Postdoctoral Fellowship on my first submission, as well as an American Heart Association Career Development Award.

Positions, Scientific Appointments, and Honors

Positions

Activity/Occupation	Date	Field	Institution	Supervisor/Employer
Graduate Assistant   Postdoctoral Fellow   Instructor	8/2012-5/2017   5/2017-12/2018   1/2019-present	Physiology   Physiology   Physiology	LSU Health Sciences Center, New Orleans Univ. of Mississippi Medical Center   Univ. of Mississippi Medical Center	Jason Gardner   Merry Lindsey   John Hall/ Michael Hall

Honors:

2013 Paul S. Roheim Graduate Student Excellence in Research Award. Department of Physiology, LSUHSC New Orleans.

2014 Society for Experimental Biology and Medicine Young Investigator Award. Experimental Biology, San Diego, CA.

2015 American Physiological Society Caroline Tum Suden/Frances Hellebrandt Professional Opportunity Award. Experimental Biology, Boston, MA.

2018 American Physiological Society Caroline Tum Suden/Frances Hellebrandt Professional Opportunity Award Experimental Biology, San Diego, CA.

2018 University of Mississippi Medical Center Department of Medicine Research Day. Poster Competition, 1st Place.

2019 University of Mississippi Medical Center Research Day. Postdoctoral Poster Competition Award.

2020 American Physiological Society Cardiovascular Section. Research Recognition Award. Experimental Biology, San Diego, CA (canceled).

2020 University of Mississippi Medical Center Trustmark Postdoctoral Fellowship Award.

2022 University of Mississippi Excellence in Research Award—Silver Level.

Contributions to Science

Roles of immune cells and fibroblasts in cardiac remodeling. In my first year as a postdoctoral fellow at UMMC, I worked to characterize the phenotypes of macrophages and fibroblasts at different points following MI in mice using RNA-sequencing. I found that after MI, macrophages transition from an early pro-inflammatory and glycolytic phenotype to an anti-inflammatory and pro-extracellular matrix phenotype that rely on mitochondrial oxidative phosphorylation. I also found that after MI, fibroblasts display an early pro-angiogenic phenotype, and a later anti-angiogenic signature via the release of thrombospondin-1. As an Instructor, I have focused on macrophage and fibroblast metabolism as potential mechanisms of inflammation and fibrosis during cardiac remodeling. The following publications demonstrate my role in these projects.

1. Mouton AJ, do Carmo JM, da Silva AA, Omoto ACM, Hall JE. Targeting Immunometabolism during cardiorenal injury: role of conventional and alternative macrophage metabolic fuels. Front Physiol. April 2023. doi: 10.3389/fphys.2023.1139296.
2. Mouton AJ, Aitken NM, Moak SP, do Carmo JM, da Silva AA, Omoto ACM, Li X, Wang Z, Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA, Hall JE. Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction. Front Cardiovasc Med. April 2023. doi: 10.3389/fcvm.2023.1136252
3. Mouton AJ, Flynn ER, Moak SP, Aitken NM, Omoto ACM, Li X, da Silva AA, Wang Z, do Carmo JM, Hall JE. Dimethyl fumarate preserves left ventricular infarct integrity following myocardial infarction via modulation of cardiac macrophage and fibroblast oxidative metabolism. J Mol Cell Cardiol. 2021 May 21;158:38-48. doi: 10.1016/j.yjmcc.2021.05.008.
4. Mouton AJ, Hall JE. Novel Roles of Immunometabolism and Non-Myocyte Metabolism in Cardiac Remodeling and Injury. Am J Physiol Regul Integr Comp Physiol. 2020 Sep 2 doi: 10.1152/ajpregu.00188.2020. Online ahead of print. PMID: 32877243
5. Mouton AJ, Li X, Hall ME, Hall JE. Obesity, Hypertension, and Cardiac Dysfunction: Novel Roles of Immunometabolism in Macrophage Activation and Inflammation. Circ Res. 2020; 126(6):789-806. doi: 10.1161/CIRCRESAHA.119.312321. PMID: 32163341
6. Mouton AJ, Ma Y, Rivera-Gonzalez OJ, Daseke MJ, Flynn ER, Freeman TC, Garrett MR, Deleon-Pennell KY, Lindsey ML. Fibroblast polarization over the myocardial infarction time continuum shifts roles from inflammation to angiogenesis. Basic Res Cardiol 2019 114: Jan 11; 114(2):6. doi: 10.1007/s00395-019-0715-4. PMID: 30635789
7. Mouton AJ, DeLeon-Pennell KY, Rivera Gonzalez OJ, Flynn ER, Freeman TC, Saucerman JJ, Garrett MR, Ma Y, Harmancey R, and Lindsey ML. Mapping macrophage polarization over the myocardial infarction time continuum. Basic Res Cardiol 2018; Jun 4;113(4):26. doi: 10.1007/s00395-018-0686-x: PMID: 29868933
8. DeLeon-Pennell KY, Mouton AJ, Ero OK, Ma Y, Padmanabhan Iyer R, Flynn ER, Espinoza I, Musani SK, Vasan RS, Hall ME, Fox ER, Lindsey ML. LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling. Basic Res Cardiol. 2018; 113(5):40. doi: 10.1007/s00395-018-0699-5. PMID: 30132266
9. Mouton AJ, Rivera Gonzalez OJ, Kaminski AR, Moore ET, Lindsey ML. Matrix metalloproteinase-12 as an endogenous resolution promoting factor following myocardial infarction. Pharmacol Res. 2018; 137:252-258. doi: 10.1016/j.phrs.2018.10.026. PMID: 30394317
10. Mouton AJ, Rivera OJ, Lindsey ML. Myocardial infarction remodeling that progresses to heart failure: a signaling misunderstanding. Am J Physiol Heart Circ Physiol. 2018; 315(1):H71-H79. doi: 10.1152/ajpheart.00131.2018.PMID: 29600895
11. Ma Y, Mouton AJ, Lindsey ML. Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction. Transl Res. 2018; 191:15-28. doi: 10.1016/j.trsl.2017.10.001. PMID: 29106912.

Role of obesity and hypertension in exacerbating post-myocardial infarction. In this project, we demonstrated that obesity paradoxically impaired survival but mildly improved cardiac function and markers of cardiac protection in adult mice. However, when hypertension was imposed on obesity, survival was markedly impaired and cardiac function and remodeling, including fibrosis, was worsened.

1. Mouton AJ, Flynn ER, Moak SP, Li X, da Silva AA, Wang Z, do Carmo JM, Hall ME, Hall JE. Interaction of obesity and hypertension on cardiac metabolic remodeling and survival following myocardial infarction. J Am Heart Assoc. 2021 Mar 16;10(6):e018212. doi: 10.1161/JAHA.120.018212.

Effects of chronic alcohol exposure on cardiac remodeling. A major focus of our lab during my pre-doctoral career was determining the deleterious effects of chronic alcohol abuse on cardiac remodeling pathways, both in the normal heart and the pathologically hypertrophied heart. As a first author, I found that chronic alcohol exposure attenuated the compensatory hypertrophy response in rats with aortocaval fistula, and accelerated the onset of early signs of decompensated heart failure. I also found that alcohol-induced cardiac atrophy was associated with a pro-inflammatory cardiac fibroblast phenotype that contributes to cardiac inflammation and impaired anabolic signaling in cardiac myocytes. I also co-authored a study which determined that the pro-fibrotic effect of alcohol on the left ventricle was related to its ability to alter the MMP/TIMP ratio in cardiac fibroblasts. The following publications demonstrate my role in these projects

1. Mouton AJ, El Hajj EJ, Ninh VK, Siggins RW, Gardner JD. Inflammatory cardiac fibroblast phenotype underlies chronic alcohol-induced cardiac atrophy and dysfunction. Life Sci. 2020; 18:117330. doi: 10.1016/j.lfs.2020.117330. PMID: 31962130
2. Mouton AJ, Ninh VK, El Hajj EC, El Hajj MC, Gilpin NW, Gardner JD. Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload. J Mol Cell Cardiol. 2016; 97:15-23. doi: 10.1016/j.yjmcc.2016.04.010. PMID: 2710748
3. Mouton AJ, Maxi JK, Souza-Smith F, Bagby GJ, Gilpin NW, Molina PE, Gardner JD. Alcohol Vapor Inhalation as a Model of Alcohol-Induced Organ Disease. Alcohol Clin Exp Res. 2016; 40(8):1671-8. doi: 10.1111/acer.13133. PMID: 2737517489
4. Gardner JD, Mouton AJ. Alcohol effects on cardiac function. Compr Physiol. 2015; 5(2):791-802. doi: 10.1002/cphy.c140046. PMID: 25880513
5. Ninh VK, El Hajj EC, Mouton AJ, Gardner JD. Prenatal Alcohol Exposure Causes Adverse Cardiac Extracellular Matrix Changes and Dysfunction in Neonatal Mice. Cardiovasc Toxicol. 2019; 19(5):389-400. doi: 10.1007/s12012-018-09503-8. PMID: 25880513

Complete List of Published Works in my Bibliography (33 total):

https://pubmed.ncbi.nlm.nih.gov/?term=mouton+aj&sort=date