Profile

Education & Training

• Ph.D., Wake Forest University , 1979
• B.S., North Carolina State University , 1973
• M.S., Wake Forest University , 1976
• Fellowship, Boston University School of Me, 1981

Memberships

• Aha - Council On Arteriosclero

Recent Publications

All Publications

For a listing of recent publications, refer to PubMed, a service provided by the National Library of Medicine.

• WFBMC
• All

For a list of earlier publications, visit the Carpenter Library Publication Search.

Current Research:

My lab has several National Institutes of Health (NIH)-funded projects that focus on the pathogenesis of complex, chronic diseases such as atherosclerosis (i.e., hardening of the arteries), diabetes, obesity, and end-stage renal disease. We study the effect of lipid metabolism and inflammation on the development and progression of complex metabolic diseases. To accomplish the goals of our grant projects, we use an interdisciplinary approach that includes transgenic/gene-targeted mouse models of human disease, molecular biology, cell biology, biochemistry, mass spectrometry, and vascular wall biology.  

Liver ABCA1, Lipoprotein Metabolism and Atherosclerosis

ATP binding cassette transporter A1 (ABCA1) is a membrane protein that functions to assemble nascent high density lipoproteins (HDL), the so called “good form of cholesterol.” ABCA1 is expressed in most cells in the body, but the cell-specific role of the transporter in liver lipoprotein metabolism and the development of atherosclerosis is poorly understood. We developed a hepatocyte-specific ABCA1 knockout (HSKO) mouse that exhibits low plasma HDL and low density lipoprotein (LDL) concentrations (20% and 50% of normal, respectively) and elevated triglyceride (TG) concentrations compared to wild type mice. The goal of this project is to understand mechanistically how hepatocyte-specific expression of ABCA1 impacts lipoprotein metabolism and the development of atherosclerosis.  

Macrophage ABCA1, Inflammation, and Atherosclerosis

Accumulation of cholesteryl ester (CE)-laden macrophages (a type of white blood cells) in arteries is a hallmark of atherosclerosis (i.e., hardening of the arteries). Macrophages are a key cell type in innate immunity and are involved in the processing of excess lipid from apoptotic and necrotic cells at sites of inflammation. ABCA1 is a membrane protein that is required to remove excess lipid from macrophages by transporting phospholipid (PL) and free cholesterol (FC) across the cell membrane to combine with apolipoprotein A-I (apoA-I), forming nascent HDLs that transport excess lipid back to the liver for excretion. Genetic absence of ABCA1 results in Tangier disease, which is characterized by CE-loaded macrophages, absence of plasma HDL, and premature atherosclerosis. Results from published studies of ABCA1 total body knockout mice suggest an association between ABCA1 expression, atherosclerosis, inflammation, and insulin resistance. However, the nearly ubiquitous expression of ABCA1 in the body has made it difficult to determine the specific role of macrophage ABCA1 in the pathogenesis of these diseases in total body ABCA1 knockout mice. To address these gaps in knowledge, we developed macrophage-specific ABCA1 KO (MSKO) mice. The goal of this proposal is to use MSKO mice to determine the mechanisms by which macrophage-specific deletion of ABCA1 expression: 1) increases macrophage inflammation, 2) affects atherosclerosis development, and 3) increases development of obesity and insulin resistance.  

Atheroprotective Mechanisms of Borage and Echium Oils

This project is part of the Wake Forest Center for Botanical Lipids and Inflammatory Disease Prevention. We have demonstrated that Echium oil (EO), a botanical oil enriched in stearidonic acid (18:4 n-3), the immediate downstream product of the rate-limiting delta-6 desaturation of alpha-linolenic acid (18:3 n-3), reduces plasma lipids, inflammation, and atherosclerosis similar to fish oil (FO), but we do not know the exact mechanisms for the protection. EO also contains 11% gamma-linolenic acid (GLA, 18:3 n-6), which is the delta-6 desaturation product of linoleic acid (18:2 n-6) and thus, can provide substrate for conversion to anti-inflammatory series 1 prostaglandin (PGE1). However, we do not know whether a botanical oil that is enriched in GLA, such as borage oil (BO; 25% GLA), is equally protective or less protective than EO. The goal of this project is to investigate whether EO and BO are equally atheroprotective and to determine anti-atherogenic mechanisms of these botanical oils. Our primary hypothesis is that both EO and BO will reduce atherosclerosis relative to palm oil (PO), by attenuating the rise of proinflammatory monocytes in blood and the trafficking of monocytes into atherosclerotic lesions (specific aim 1). Furthermore, we hypothesize that EO and BO will result in alternative activation of macrophages, relative to PO, resulting in less inflammatory macrophages (specific aim 2). Finally, we propose that the polyunsaturated fatty acid (PUFA)-induced macrophage alternative activation will occur through multiple mechanisms that include antagonism of proinflammatory gene transactivation, PPARgamma-dependent transactivation of anti-inflammatory genes, and PPARgamma-dependent transrepression of pro-inflammatory genes (specific aim 3). The proposed mechanistic studies should allow us to determine the best botanical oils or combinations to move into human trials to test for reduction of atherosclerosis risk and inflammation and to improve our basic information regarding the mechanism of action of botanical oils in chronic disease prevention. 

ApoL1 and End-stage Kidney Disease in African-Americans

ApoL1 is an apolipoprotein that binds to HDL and protects humans from African sleeping sickness caused by the parasite Trypansoma brucei brucei. When apoL1 is internalized by trypanosomes, it trafficks to the lysosome where it forms pores and causes the trypanosome to swell and rupture.  However, some subspecies of trypanosomes, for instance T. b. rhodesiense, produce a serum resistance factor that blocks the action of apoL1, resulting in African sleeping sickness. African-Americans produce several variant forms of apoL1 that do not bind to serum resistance factor, allowing killing of trypanosomes. However, these African-American variants of apoL1 are associated with a 7-10 fold increased risk of end stage kidney disease. The Parks lab is involved in a new collaborative NIH study (Dr. Barry Freedman, PI)   that seeks to understand mechanistically how the risk variant forms of apoL1 result in increased risk of end-stage kidney disease in African-Americans. 

Our lab's LCAT antibodies are available from  Novus Biologicals. 

Publications: 

• Link to Dr. Parks' publications in the PubMed database