Andrew J Morris, PhD

Research Program: Cancer Prevention and Population Sciences Faculty Rank: Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Pharmacology UAMS, Research CAVHS

Cancer Research Interest

• Disease Site Focus: No Specific Disease Site
• Research Focus Area: Detection, Treatment, Informatics, Carcinogenesis
• Type of Research: Population Sciences, Translational, Basic
• Research Keywords: Environmental Toxicology, metabolomics, lipidomics, bioactive lipids
• Research Interest Statement: Andrew J. Morris, Ph.D. Professor Pharmacology and Toxicology Research Investigator, Central Arkansas VA Healthcare System. BSc. 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. Of relevance to the focus of the Cancer Center, I am interested in using mass spectrometry based methods to measure toxic environmental chemicals in support of population health studies, notably the military Millennium Cohort and Million Veteran Program. This includes roles in the VA Military Exposure Research Program and VA/DOD participation in population health/environmental carcinogenesis focus areas of the Cancer Moonshot program. I have also used lipidomics and metabolomics approaches to study dysregulation of metabolism in cancer. 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: 1. 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 2. 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. 3. 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. 4. 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 5. 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: 1. 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 2. 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. 3. 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 4. 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 5. 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: 1. 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. 2. 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. 3. 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 4. 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 5. 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. Personnel. Rushita Bagchi, Ph.D., Assistant Professor Desislava Marinkova, Ph. D, Post-Doctoral Fellow Lauren Havens, BA, Analytical Laboratory Manager Grace Purvis, BSc, Laboratory Manager

Contact Information

• Email Address: AJMORRIS@UAMS.EDU
• Profiles Research Networking Software: View Profile

Active Grants

• NIH/Nat. Cancer Institute – 1R37CA282349
  “Ryanodine Receptors as Therapeutic Targets to Prevent Doxorubicin-Induced Lymphatic Dysfunction”
  Co-Investigator
  08/10/23 – 07/31/28

Publications

• Li J, Yang L, Song J, [et al., including Morris AJ]. Neurotensin accelerates atherosclerosis and increases circulating levels of short-chain and saturated triglycerides. Atherosclerosis. 2024:117479. PMID: 38423808.
• Arun P, Wilder DM, Morris AJ, [et al.]. Cerebrospinal Fluid Levels of Lysophosphatidic Acids Can Provide Suitable Biomarkers of Blast-Induced Traumatic Brain Injury. Journal of neurotrauma. 2023. PMID: 37279302.
• Tang X, Morris AJ, Deken MA, Brindley DN. Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not. Cancers. 2023 15(11). PMID: 37296899. PMCID: PMC10251959.
• Tenlep SYN, Weaver M, Chen J, [et al., including Morris AJ]. Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice. Toxicology letters. 2023 374:31-39. PMID: 36493961. PMCID: PMC9869283.
• Tripathi H, Shindo K, Donahue RR, [et al., including Morris AJ]. Myeloid-Specific Deletion of Lipid Plpp3 (Phosphate Phosphatase 3) Increases Cardiac Inflammation After Myocardial Infarction. Arteriosclerosis, thrombosis, and vascular biology. 2023 43(2):379-381. PMID: 36453277. PMCID: PMC10503312.
• Kipp ZA, Martinez GJ, Bates EA, [et al., including Morris AJ]. Bilirubin Nanoparticle Treatment in Obese Mice Inhibits Hepatic Ceramide Production and Remodels Liver Fat Content. Metabolites. 2023 13(2). PMID: 36837834. PMCID: PMC9965094.
• Bates EA, Kipp ZA, Martinez GJ, [et al., including Morris AJ]. Suppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease. Biomolecules. 2023 13(2). PMID: 36830621. PMCID: PMC9953728.
• Morgan S, Mottaleb MA, Kraemer MP, [et al., including Morris AJ]. Effect of lifestyle-based lipid lowering interventions on the relationship between circulating levels of per-and polyfluoroalkyl substances and serum cholesterol. Environmental toxicology and pharmacology. 2023 98:104062. PMID: 36621559. PMCID: PMC9992109.
• Van Hoose PM, Yang L, Kraemer M, [et al., including Morris AJ]. Lipid phosphate phosphatase 3 in smooth muscle cells regulates angiotensin II-induced abdominal aortic aneurysm formation. Scientific reports. 2022 12(1):5664. PMID: 35383201. PMCID: PMC8983654.
• Petriello MC, Mottaleb MA, Serio TC, [et al., including Morris AJ]. Serum concentrations of legacy and emerging per- and polyfluoroalkyl substances in the Anniston Community Health Surveys (ACHS I and ACHS II). Environment international. 2022 158:106907. PMID: 34763231. PMCID: PMC9131314.
• Araujo N, Sledziona J, Noothi SK, [et al., including Morris AJ]. Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity. Frontiers in oncology. 2022 12:860446. PMID: 35425699. PMCID: PMC9004617.
• Hinds TD Jr, Kipp ZA, Xu M, [et al., including Morris AJ]. Adipose-Specific PPARα Knockout Mice Have Increased Lipogenesis by PASK-SREBP1 Signaling and a Polarity Shift to Inflammatory Macrophages in White Adipose Tissue. Cells. 2021 11(1). PMID: 35011564. PMCID: PMC8750478.
• Sui Y, Meng Z, Chen J, [et al., including Morris AJ]. Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice. Environmental health perspectives. 2021 129(12):127001. PMID: 34851150. PMCID: PMC8634903.
• Matas-Rico E, Frijlink E, van der Haar Àvila I, [et al., including Morris AJ]. Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8(+) T cells. Cell reports. 2021 37(7):110013. PMID: 34788605. PMCID: PMC8761359.
• Mottaleb MA, Ding QX, Pennell KG, [et al., including Morris AJ]. Direct injection analysis of per and polyfluoroalkyl substances in surface and drinking water by sample filtration and liquid chromatography-tandem mass spectrometry. Journal of chromatography. A. 2021 1653:462426. PMID: 34352431. PMCID: PMC8935770.
• Supinski GS, Schroder EA, Wang L, [et al., including Morris AJ]. Mitoquinone mesylate (MitoQ) prevents sepsis-induced diaphragm dysfunction. Journal of applied physiology (Bethesda, Md. : 1985). 2021 131(2):778-787. PMID: 34197233. PMCID: PMC8409922.
• Deng P, Valentino T, Flythe MD, [et al., including Morris AJ]. Untargeted Stable Isotope Probing of the Gut Microbiota Metabolome Using (13)C-Labeled Dietary Fibers. Journal of proteome research. 2021 20(5):2904-2913. PMID: 33830777. PMCID: PMC8784920.
• Finlin BS, Memetimin H, Zhu B, [et al., including Morris AJ]. Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism. JCI insight. 2021 6(6). PMID: 33571166. PMCID: PMC8026187.
• Zhu N, Zhang C, Prakash A, [et al., including Morris A]. Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR. EMBO molecular medicine. 2021 13(3):e12651. PMID: 33474818. PMCID: PMC7933950.
• Henry N, Frank J, McLouth C, [et al., including Morris A]. Short Chain Fatty Acids Taken at Time of Thrombectomy in Acute Ischemic Stroke Patients Are Independent of Stroke Severity But Associated With Inflammatory Markers and Worse Symptoms at Discharge. Frontiers in immunology. 2021 12:797302. PMID: 35126360. PMCID: PMC8807638.
• Eke J, Banks L, Mottaleb MA, [et al., including Morris AJ]. Dual-Functional Phosphorene Nanocomposite Membranes for the Treatment of Perfluorinated Water: An Investigation of Perfluorooctanoic Acid Removal via Filtration Combined with Ultraviolet Irradiation or Oxygenation. Membranes. 2020 11(1). PMID: 33375603. PMCID: PMC7824437.
• Deng P, Wang C, Wahlang B, [et al., including Morris AJ]. Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice. Toxicology and applied pharmacology. 2020 409:115301. PMID: 33096110. PMCID: PMC7725976.
• Tripathi H, Al-Darraji A, Abo-Aly M, [et al., including Morris AJ]. Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction. Journal of molecular and cellular cardiology. 2020 149:95-114. PMID: 33017574. PMCID: PMC7744112.
• Xiang B, Zhang G, Zhang Y, [et al., including Morris AJ]. Calcium Ion Chelation Preserves Platelet Function During Cold Storage. Arteriosclerosis, thrombosis, and vascular biology. 2020:ATVBAHA120314879. PMID: 33176450. PMCID: PMC8158249.
• Thalman C, Horta G, Qiao L, [et al., including Morris AJ]. Correction: Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders. Molecular psychiatry. 2020 25(11):3108. PMID: 30602735. PMCID: PMC7962560.
• Smyth SS, Kraemer M, Yang L, [et al., including Morris AJ]. Roles for lysophosphatidic acid signaling in vascular development and disease. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020 1865(8):158734. PMID: 32376340.
• Guo Y, Ye Q, Deng P, [et al., including Morris AJ]. Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression. Nature communications. 2020 11(1):3243. PMID: 32591507. PMCID: PMC7320137.
• Hoffman JB, Petriello MC, Morris AJ, [et al.]. Prebiotic inulin consumption reduces dioxin-like PCB 126-mediated hepatotoxicity and gut dysbiosis in hyperlipidemic Ldlr deficient mice. Environmental pollution (Barking, Essex : 1987). 2020 261:114183. PMID: 32105967. PMCID: PMC7220843.
• Mottaleb MA, Petriello MC, Morris AJ. High-Throughput UHPLC-MS/MS Measurement of Per- and Poly-Fluorinated Alkyl Substances in Human Serum. Journal of analytical toxicology. 2020 44(4):339-347. PMID: 31776573. PMCID: PMC7299301.
• Finlin BS, Memetimin H, Zhu B, [et al., including Morris AJ]. The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans. The Journal of clinical investigation. 2020 130(5):2319-2331. PMID: 31961829. PMCID: PMC7190997.
• Arun P, Rossetti F, DeMar JC, [et al., including Morris AJ]. Antibodies Against Lysophosphatidic Acid Protect Against Blast-Induced Ocular Injuries. Frontiers in neurology. 2020 11:611816. PMID: 33384658. PMCID: PMC7769950.
• Deng P, Hoffman JB, Petriello MC, [et al., including Morris AJ]. Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice. Journal of lipid research. 2020 61(1):45-53. PMID: 31604806. PMCID: PMC6939596.
• Onono FO, Morris AJ. Phospholipase D and Choline Metabolism. Handbook of experimental pharmacology. 2020 259:205-218. PMID: 32086667. PMCID: PMC7768751.
• Chen S, Henderson A, Petriello MC, [et al., including Morris AJ]. Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction. Cell metabolism. 2019 30(6):1141-1151.e5. PMID: 31543404.
• Kraemer MP, Mao G, Hammill C, [et al., including Morris AJ]. Effects of diet and hyperlipidemia on levels and distribution of circulating lysophosphatidic acid. Journal of lipid research. 2019 60(11):1818-1828. PMID: 31484695. PMCID: PMC6824489.
• Mueller PA, Yang L, Ubele M, [et al., including Morris AJ]. Coronary Artery Disease Risk-Associated Plpp3 Gene and Its Product Lipid Phosphate Phosphatase 3 Regulate Experimental Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2019 39(11):2261-2272. PMID: 31533471. PMCID: PMC6812632.
• Zhu Z, Chen J, Wang G, [et al., including Morris AJ]. Ceramide regulates interaction of Hsd17b4 with Pex5 and function of peroxisomes. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2019 1864(10):1514-1524. PMID: 31176039. PMCID: PMC6679753.
• Deng P, Li X, Petriello MC, [et al., including Morris AJ]. Application of metabolomics to characterize environmental pollutant toxicity and disease risks. Reviews on environmental health. 2019 34(3):251-259. PMID: 31408434. PMCID: PMC6915040.
• Mao G, Smyth SS, Morris AJ. Regulation of PLPP3 gene expression by NF-κB family transcription factors. The Journal of biological chemistry. 2019 294(38):14009-14019. PMID: 31362988. PMCID: PMC6755815.
• Larian N, Ensor M, Thatcher SE, [et al., including Morris AJ]. Pseudomonas aeruginosa-derived pyocyanin reduces adipocyte differentiation, body weight, and fat mass as mechanisms contributing to septic cachexia. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2019 130:219-230. PMID: 31078726. PMCID: PMC6557674.
• Park SY, Yang JS, Li Z, [et al., including Morris AJ]. The late stage of COPI vesicle fission requires shorter forms of phosphatidic acid and diacylglycerol. Nature communications. 2019 10(1):3409. PMID: 31363100. PMCID: PMC6667475.
• Jackson EN, Thatcher SE, Larian N, [et al., including Morris AJ]. Effects of Aryl Hydrocarbon Receptor Deficiency on PCB-77-Induced Impairment of Glucose Homeostasis during Weight Loss in Male and Female Obese Mice. Environmental health perspectives. 2019 127(7):77004. PMID: 31306034. PMCID: PMC6794491.
• Morris AJ. Phospholipases D: making sense of redundancy and duplication. Bioscience reports. 2019 39(6). PMID: 31189747. PMCID: PMC6597845.
• AlSiraj Y, Chen X, Thatcher SE, [et al., including Morris AJ]. XX sex chromosome complement promotes atherosclerosis in mice. Nature communications. 2019 10(1):2631. PMID: 31201301. PMCID: PMC6643208.
• Yang L, Kraemer M, Fang XF, [et al., including Morris AJ]. LPA receptor 4 deficiency attenuates experimental atherosclerosis. Journal of lipid research. 2019 60(5):972-980. PMID: 30796085. PMCID: PMC6495174.
• Edgar RJ, van Hensbergen VP, Ruda A, [et al., including Morris AJ]. Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides. Nature chemical biology. 2019 15(5):463-471. PMID: 30936502. PMCID: PMC6470023.