David A. Ford, Ph.D.
Biochemical mechanisms responsible for the pathophysiological sequelae of cardiovascular diseases, including ischemic heart disease and atherosclerosis.
Office: DRC, Room 325
Phone: (314) 977-9264
Ph.D., 1985, University of Missouri-Columbia
We are interested in biochemical mechanisms responsible for the pathophysiological sequelae of cardiovascular diseases including ischemic heart disease and atherosclerosis. Areas of research focus on enzymic and free radical targeting of membrane phospholipids, alterations in lipid metabolism, and alterations in signaling pathways as mechanisms involved in cardiovascular diseases. We combine our expertise using physiological models of disease coupled with expertise in mass spectrometry and bioorganic techniques to reveal new mechanistic insights into cardiovascular disease.
- Platelet-activating factor quantification using reversed phase liquid chromatography and selected reaction monitoring in negative ion mode.
Pike DP, Hartman CL, et al. Lipids. (2016) Oct 18 [Epub ahead of print].
- Formation of chlorinated lipids post-chlorine gas exposure.
Ford DA, Honavar J, et al. J Lipid Res. (2016) 57(8):1529-1540.
- Intestinal phospholipid remodeling is required for dietary lipid uptake and survival on a high-fat diet.
Wang B, Rong X, et al. Cel Metab. (2016) 23(3):492-504.
- Akt-mediated FoxO1 inhibition is required for liver regeneration.
Pauta M, Rotllan N, et al. Hepatology. (2016) 63(5):1660-1674.
- Identification of glutathione adducts of alpha-chlorofatty aldehydes produced in activated neutrophils.
Duerr MA, Aurora R, Ford DA. J Lipid Res. (2015) 56(5):1014-1024.
- Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion.
Rong X, Wang B, et al. Elife. (2015) 4:e06557.
- Dipeptidyl peptidase-4 inhibition ameliorates western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function.
Aroor AR, Habibi J, et al. Diabetes. (2015) 64(6):1988-2001.
- PON3 knockout mice are susceptible to obesity, gallstone formation, and atherosclerosis.
Shih DM, Yu JM, et al. FASEB J. (2015) 29(4):1185-1197.
Calcium-independent phospholipase A2 mediates CREB phosphorylation and c-fos expression during ischemia.
Scott D. Williams and David A. Ford.
Am. J. Physiol. 281(1): H168-176, 2001. (PMID 11406482)
This publication was the culmination of a number of studies in our lab focusing on the role of the calcium-independent phospholipase A2 (iPLA2) as a mediator of alterations in myocardium following myocardial ischemia and was the final publication of the first graduate student in my lab at SLU. This paper linked iPLA2 to nuclear signaling via PKA in the ischemic-reperfused heart. We shifted our focus from phospholipases to HOCl mediated signaling mechanisms after these stellar studies. This field is open to further investigation in my lab.
Proposed mechanisms mediating CREB phosphorylation in response to myocardial ischemia. LPC, choline-containing lysoglycerophospholipids (i.e., lysoplasmenylcholine and lysophosphatidylcholine).
Metabolism of myeloperoxidase-derived 2-chlorohexadecanal.
Kristin R. Wildsmith, Carolyn J. Albert, Dhanam S. Anbukumar, and David A. Ford.
J. Biol. Chem. 281(25):16849-16860, 2006 (PMID 16611638)
Our laboratory discovered that plasmalogens are targeted by hypochlorous acid, which is produced by the activity of myeloperoxidase in activated neutrophils, monocytes and macrophages. While the first paper describing this pathway was significant, this publication resulting from the tremendous work led by graduate student, Kristin Wildsmith, and Lab Manager, Carolyn Albert, with the aide of graduate student, Dhanam Subramanian Anbukumar, showed the many chlorinated lipid species that could be produced as a result of the reaction of plasmalogens and hypochlorous acid. The work from these studies introduced us to the chlorinated lipidome. The study of these lipids and their role in ischemia/reperfusion, atherosclerosis, sepsis and infectious disease remains an evolving focus of our lab.
Alpha-Chlorofatty acid accumulates in activated monocytes and causes apoptosis through reactive oxygen species production and endoplasmic reticulum stress.
Wen-yi Wang, Carolyn J. Albert, and David A. Ford.
Arterioscler. Thromb. Vasc. Biol. 34(3):523-532, 2014. (PMID 24371082)
Post-doc Wen-yi Wang showed the amounts of alpha-chlorofatty acid produced in human monocytes and then revealed the mechanism by which these lipids elicit monocyte apoptosis through the production of hydrogen peroxide and ER stress. Furthermore, showing these pathways are active in immortalized cell lines, such as the human monocytic cell line, THP-1, has provided our lab with a useful tool to further examine mechanisms and receptors through which chlorinated lipids elicit their cellular effects. This paper illustrates a current area of investigation in the lab.
2-ClHA induces apoptosis in primary human monocytes, THP-1 monocytes, and RAW 264.7 macrophages.