Professor, Pharmacology and Toxicology
Mehta/Stebbins Chair in Cardiovascular Research
Research Career Scientist, Central Arkansas VA Healthcare System
- B.Sc. First Class Honours in Biochemistry, University of Bristol, 1984
- Ph.D. with Robert H Michell FRS, University of Birmingham, 1988 “Metabolism of Inositol 1,4,5, Tris Phosphate”
- Post-Doctoral University of North Carolina at Chapel Hill 1988-92
Research in my laboratory has been and is currently primarily supported by grants from the Veterans Health Administration, National Institutes of Health, and Department of Defense.
I am broadly interested in understanding interactions between genetic, behavioral, and environmental risk factors for non-communicable diseases. We use a multidisciplinary approach that combines biochemical, molecular genetic and cell biological methods with preclinical models and population health studies.
Almost 20 years ago, my laboratory and colleagues identified and characterized genes involved in synthesis and metabolism of phosphatidic acid that turned out to play key roles in bioactive lipid signaling. One of these genes, PLPP3, is a heritable risk factor for coronary artery disease. The product of this gene is an integral membrane lipid phosphatase that can inactivate the bioactive lipid lysophosphatidic acid (LPA). With Susan Smyth we have shown that PLPP3 is normally protective against experimental atherosclerosis. Studies using mouse models with inducible/tissue specific post-natal inactivation of PLPP3, and other genes and receptors involved in LPA metabolism and signaling identify broad roles for this LPA/LPP3 nexus in vascular inflammation and pathologies that include aortic aneurysms and calcific aortic valve disease. Recent publications include:
- Van Hoose PM, Yang L, Kraemer M, Ubele M, Morris AJ, Smyth SS. Lipid phosphate phosphatase 3 in smooth muscle cells regulates angiotensin II-induced abdominal aortic aneurysm formation. Sci Rep. 2022 12(1):5664. PMID: 35383201
- Kraemer M, Mao G, Hammill C, Yan B, Li Y, Onono F, Smyth SS, Morris AJ. Effects of diet and hyperlipidemia on levels and distribution of circulating lysophosphatidic acid. J Lipid Res. 2019;60(11) 1818-1828 PMID: 31484695.
- Mao G, Smyth SS, Morris AJ. Regulation of PLPP3 gene expression by NF-kB family transcription factors. J Biol Chem. 2019 294 (38) 14009-14019 PMID: 31362988.
- Mueller PA, Yang L, Ubele M, Mao G, Brandon J, Vandra J, Nichols TC, Escalante-Alcalde D, Morris AJ, Smyth SS. Coronary Artery Disease Risk-Associated Plpp3 Gene and Its Product Lipid Phosphate Phosphatase 3 Regulate Experimental Atherosclerosis. Arterioscler Thromb Vasc Biol. 2019 39(11):2261-2272 PMID: 31533471
- Yang L, Kraemer M, Fang XF, Angel PM, Drake RR, Morris AJ, Smyth SS. LPA receptor 4 deficiency attenuates experimental atherosclerosis. J Lipid Res. 2019 60(5):972-980. PMID: 30796085
To support our interests in lipid metabolism and signaling, we developed expertise in applications of biomedical mass spectrometry for identification, measurement, and structural characterization of lipids and related small molecule metabolites. This encompasses large scale targeted and untargeted measurements using multistage/high resolution instruments (metabolomics and lipidomics), use of stable isotope tracers and informatic methods for data analysis. Current areas of interest include metabolism of dietary lipids, lipid peroxidation, and studies of lipid and lipid-derived biomarkers for diagnosis and treatment of human health conditions. For example, we have studied trimethylamine N-oxide which is a circulating product of microbial metabolism of dietary choline and carnitine that associates with increased cardiovascular disease risk. Recent publications include:
- Chen S, Henderson, A. Petriello, M.C., Romano, KA, Gearing, M., Miao, J, Schell, M, Sandoval-Espinola, WJ, Tao J, Sha, B, Graham M, Crooke, F, Kleinridders A, Balskus, EP, Rey, FE, Morris, AJ, Biddinger, SB. Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction. Cell Metabolism 30(6):1141-1151 PMID: 31543404
- Petriello MC, Charnigo R, Sunkara M, Soman S, Pavuk M, Birnbaum L, Morris AJ, Hennig B. Relationship between serum trimethylamine N-oxide and exposure to dioxin-like polluants. Environ Res. 2018 Apr;162:211-218. PMID: 29353125.
- Deng P, Hoffman JB, Petriello MC, Wang CY, Li XS, Kraemer MP, Morris AJ, Hennig B. Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice.J Lipid Res. 2019 61(1):45-53. PMID: 31604806
- Edgar RJ, van Hensbergen VP, Ruda A, Turner AG, Deng P, Le Breton Y, El-Sayed NM, Belew AT, McIver KS, McEwan AG, Morris AJ, Lambeau G, Walker MJ, Rush JS,Korotkov KV, Widmalm G, van Sorge NM, Korotkova N. Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides. Nat Chem Biol. 2019 May;15(5):463-471. PMID: 30936502
- Li J, Song J, Zaytseva YY, Liu Y, Rychahou P, Jiang K, Starr ME, Kim JT, Harris JW, Yiannikouris FB, Katz WS, Nilsson PM, Orho-Melander M, Chen J, Zhu H, Fahrenholz T, Higashi RM, Gao T, Morris AJ, Cassis LA, Fan TW, Weiss HL, Dobner PR, Melander O, Jia J, Evers BM. An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature. 2016 533(7603):411-5. PMID: 27193687
We use mass spectrometry methods to study health effects of human exposure to environmental chemicals in preclinical models and human subjects. I direct an analytical laboratory at the Central Arkansas VA Healthcare System that provides biomonitoring services to support population health research including studies of Veterans and Active-Duty Military personnel enrolled in the Millennium Cohort and Million Veteran Program. A current focus is on per and polyfluorinated substances which are manmade surfactant chemicals with toxic effects in preclinical models that can be detected in the blood of almost all adult Americans and are of particular concern to the military because of their widespread use in firefighting foams. Recent publications include:
- Petriello MC, Mottaleb MA, Serio TC, Balyan B, Cave MC, Pavuk M, Birnbaum LS, Morris AJ. Serum concentrations of legacy and emerging per- and polyfluoroalkyl substances in the Anniston Community Health Surveys (ACHS I and ACHS II). Environ Int. 2022 158:106907. doi: 10.1016/j.envint.2021.106907. Epub 2021 Nov 8. PMID: 34763231.
- Mottaleb MA, Ding QX, Pennell KG, Haynes EN, Morris AJ. Direct injection analysis of per and polyfluoroalkyl substances in surface and drinking water by sample filtration and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2021 13;1653:462426. PMID: 34352431.
- Mottaleb, MA, Petriello, MC and Morris, AJ. High throughput UHPLC MS/MS measurement of Per and Poly Fluorinated Alkyl Substances (PFAS) in human serum. J. Anal. Tox, 2020 18;44(4):339-347 PMID: 31776573
- Sui Y, Meng Z, Chen J, Liu J, Hernandez R, Gonzales MB, Gwag T, Morris AJ, Zhou C. Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice. Environ Health Perspect. 2021 129(12):127001. PMID: 34851150
- Jackson EN, Thatcher SE, Larian N, English V, Soman S, Morris AJ, Weng J, Stromberg A, Swanson HI, Pearson K, Cassis LA. Effects of Aryl Hydrocarbon Receptor Deficiency on PCB-77-Induced Impairment of Glucose Homeostasis during Weight Loss in Male and Female Obese Mice. Environ Health Perspect. 2019 127(7):77004. PMID: 31306034.
- Rushita Bagchi, Ph.D., Assistant Professor
- Desislava Marinkova, Ph.D., Post-Doctoral Fellow
- Lauren Havens, B.A., Analytical Laboratory Manager
- Grace Purvis, B.Sc., Laboratory Manager
- Kelsie Hartley, B.Sc., Analytical Laboratory Technician