Profile

John S. Parks, Ph.D.Wake Forest School of Medicine

John S. Parks, Ph.D.

Section Chief,
Professor,


Contact Information

Academic: 336-716-2145 | Department: 336-716-2145

Email: jparks@wakehealth.edu

Education & Training

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

Memberships

  • Aha - Council On Arteriosclero
John S. Parks, Ph.D.

John S. Parks, Ph.D.

Section Chief, Molecular Medicine
Professor, Molecular Medicine
Office of Women in Medicine and Science
Center on Diabetes, Obesity, and Metabolism

Research Interests

ATP-Binding Cassette Transporters; Cholesterol; Lipoproteins, HDL; Liver; Apolipoprotein A-I
More »

Contact Information

Academic: 336-716-2145 | Department: 336-716-2145

Email: jparks@wakehealth.edu

Recent Publications

Dietary cholesterol effects on adipose tissue inflammation. Chung S, Parks JS.. Curr Opin Lipidol. 2016;27(1):19-25.

Characterization of circulating APOL1 protein complexes in African Americans. Weckerle A, Snipes JA, Cheng D, Gebre AK, Reisz JA, Murea M, Shelness GS, Hawkins GA, Furdui CM, Freedman BI, Parks JS, Ma L.. J Lipid Res. 2016;57(1):120-130.

A systematic investigation of structure/function requirements for the apolipoprotein A-I/lecithin cholesterol acyltransferase interaction loop of high-density lipoprotein. Gu X, Wu Z, Huang Y, Wagner MA, Baleanu-Gogonea C, Mehl RA, Buffa JA, DiDonato AJ, Hazen LB, Fox PL, Gogonea V, Parks JS, DiDonato JA, Hazen SL.. J Biol Chem. 2016;291(12):6386-6395.

Myeloid deletion of alpha1AMPK exacerbates atherosclerosis in LDL receptor knockout (LDLRKO) mice. Cao Q, Cui X, Wu R, Zha L, Wang X, Parks JS, Yu L, Shi H, Xue B.. Diabetes. 2016;65(6):1565-1576.

Deficiency of ATP-binding cassette transporters A1 and G1 in endothelial cells accelerates atherosclerosis in mice. Westerterp M, Tsuchiya K, Tattersall IW, Fotakis P, Bochem AE, Molusky MM, Ntonga V, Abramowicz S, Parks JS, Welch C, Kitajewski J, Accili D, Tall AR.. Arterioscler Thromb Vasc Biol. 2016;36(7):1328-1337.

Localization of APOL1 protein and mRNA in the human kidney: nondiseased tissue, primary cells, and immortalized cell lines. Ma L, Shelness GS, Snipes JA, Murea M, Antinozzi PA, Cheng D, Saleem MA, Satchell SC, Banas B, Mathieson PW, Kretzler M, Hemal AK, Rudel LL, Petrovic S, Weckerle A, Pollak MR, Ross MD, Parks JS, Freedman BI.. J Am Soc Nephrol. 2015;26(2):339-348.

Uncleaved ApoM signal peptide is required for formation of large ApoM/sphingosine 1-phosphate (S1P)-enriched HDL particles. Liu M, Allegood J, Zhu X, Seo J, Gebre AK, Boudyguina E, Cheng D, Chuang CC, Shelness GS, Spiegel S, Parks JS.. J Biol Chem. 2015;290(12):7861-7870.

Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver. Shewale SV, Boudyguina E, Zhu X, Shen L, Hutchins PM, Barkley RM, Murphy RC, Parks JS.. J Lipid Res. 2015;56(6):1191-1205.

Biogenesis and cytotoxicity of APOL1 renal-risk variant proteins in hepatocytes and hepatoma cells. Cheng D, Weckerle A, Yu Y, Ma L, Zhu X, Murea M, Freedman BI, Parks JS, Shelness GS.. J Lipid Res. 2015;56(8):1583-1593.

LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. Ito A, Hong C, Rong X, Zhu X, Tarling EJ, Hedde PN, Gratton E, Parks J, Tontonoz P.. Elife. 2015;4():e08009.

Alterations of a cellular cholesterol metabolism network are a molecular feature of obesity-related type 2 diabetes and cardiovascular disease. Ding J, Reynolds LM, Zeller T, Muller C, Mstat KL, Nicklas BJ, Kritchevsky SB, Huang Z, Fuente A, Soranzo N, Settlage RE, Chuang CC, Howard T, Xu N, Goodarzi MO, Ida Chen YD, Rotter JI, Siscovick DS, Parks JS, Murphy S, Jacobs DR Jr,.. Diabetes. 2015;64(10):3464-3474.

Characterization of APOA-I and HDL metabolism in an endothelial specific ABCA1 deficient mouse model [abstract]. Hasballa R, Rohrer L, Fotakis P, Zannis V, Parks J, von Eckardstein A.. Atherosclerosis. 2015;241(1):E43.

Characterization of circulating APOL1 complexes and their kidney distribution in African Americans [abstract]. Ma L, Weckerle A, Snipes JA, Cheng D, Gebre AK, Murea M, Hawkins GA, Parks JS, Freedman BI.. J Am Soc Nephrol. 2015;26(Abstract Suppl):708A.

An abundant dysfunctional apolipoprotein A1 in human atheroma. Huang Y, Didonato JA, Levison BS, Schmitt D, Li L, Wu Y, Buffa J, Kim T, Gerstenecker GS, Gu X, Kadiyala CS, Wang Z, Culley MK, Hazen JE, Didonato AJ, Fu X, Berisha SZ, Peng D, Nguyen TT, Liang S, Chuang CC, Cho L, Plow EF,.. Nat Med. 2014;20(2):193-203.

Hepatic apolipoprotein M (apoM) overexpression stimulates formation of larger apoM/sphingosine 1-phosphate-enriched plasma high density lipoprotein. Liu M, Seo J, Allegood J, Bi X, Zhu X, Boudyguina E, Gebre AK, Avni D, Shah D, Sorci-Thomas MG, Thomas MJ, Shelness GS, Spiegel S, Parks JS.. J Biol Chem. 2014;289(5):2801-2814.

Myeloid cell-specific ATP-binding cassette transporter A1 deletion has minimal impact on atherogenesis in atherogenic diet-fed low-density lipoprotein receptor knockout mice. Bi X, Zhu X, Gao C, Shewale S, Cao Q, Liu M, Boudyguina E, Gebre AK, Wilson MD, Brown AL, Parks JS.. Arterioscler Thromb Vasc Biol. 2014;34(9):1888-1899.

Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development. Cao Q, Rong S, Repa JJ, Clair RS, Parks JS, Mishra N.. Arterioscler Thromb Vasc Biol. 2014;34(9):1871-1879.

Dietary cholesterol promotes adipocyte hypertrophy and adipose tissue inflammation in visceral, but not in subcutaneous, fat in monkeys. Chung S, Cuffe H, Marshall SM, McDaniel AL, Ha JH, Kavanagh K, Hong C, Tontonoz P, Temel RE, Parks JS.. Arterioscler Thromb Vasc Biol. 2014;34(9):1880-1887.

Lipoprotein metabolism and transendothelial apolipoprotein A-I transport in mice with an endothelium specific knock-out of ATP binding cassette transporter A1 [abstract]. Hasballa R, Rohrer L, Fotakis P, Zannis VI, Parks JS, von Eckardstein A.. Atherosclerosis. 2014;235(2):e21.

Inhibiting DNA Methylation by 5-Aza-2'-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation. Cao Q, Wang X, Jia L, Mondal AK, Diallo A, Hawkins GA, Das SK, Parks JS, Yu L, Shi H, Shi H, Xue B.. Endocrinology. 2014;155(12):4925-4938.

An ACACB variant implicated in diabetic nephropathy associates with body mass index and gene expression in obese subjects. Ma L, Murea M, Snipes JA, Marinelarena A, Kruger J, Hicks PJ, Langberg KA, Bostrom MA, Cooke JN, Suzuki D, Babazono T, Uzu T, Tang SC, Mondal AK, Sharma NK, Kobes S, Antinozzi PA, Davis M, Das SK, Rasouli N, Kern PA,.. PLoS One. 2013;8(2):e56193.

Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Sene A, Khan AA, Cox D, Nakamura RE, Santeford A, Kim BM, Sidhu R, Onken MD, Harbour JW, Hagbi-Levi S, Chowers I, Edwards PA, Baldan A, Parks JS, Ory DS, Apte RS.. Cell Metab. 2013;17(4):549-561.

Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice. Westerterp M, Murphy AJ, Wang M, Pagler TA, Vengrenyuk Y, Kappus MS, Gorman DJ, Nagareddy PR, Zhu X, Abramowicz S, Parks JS, Welch C, Fisher EA, Wang N, Yvan-Charvet L, Tall AR.. Circ Res. 2013;112(11):1456-1465.

Increased cholesterol content in gammadelta T lymphocytes differentially regulates their activation. Cheng HY, Wu R, Gebre AK, Hanna RN, Smith DJ, Parks JS, Ley K, Hedrick CC.. PLoS One. 2013;8(5):e63746.

Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice. Forrest LM, Lough CM, Chung S, Boudyguina EY, Gebre AK, Smith TL, Colvin PL, Parks JS.. Nutrients. 2013;5(7):2629-2645.

Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models. Zhu X, Chung S, Bi X, Chuang CC, Brown AL, Liu M, Seo J, Cuffe H, Gebre AK, Boudyguina E, Parks JS.. J Lipid Res. 2013;54(10):2708-2717.

ApoL1 protein in non-diseased human podocytes: endogenous synthesis versus uptake? [abstract]. Ma L, Snipes JA, Murea M, Antinozzi PA, Shelness GS, Saleem M, Satchell SC, Banas B, Mathieson PW, Kretzler M, Petrovic S, Ross MD, Pollak MR, Rudel L, Parks JS, Freedman BI.. J Am Soc Nephrol. 2013;24(Abstract Suppl):557A.

Liver ABCA1 deletion in LDLrKO mice does not impair macrophage reverse cholesterol transport or exacerbate atherogenesis. Bi X, Zhu X, Duong M, Boudyguina EY, Wilson MD, Gebre AK, Parks JS.. Arterioscler Thromb Vasc Biol. 2013;33(10):2288-2296.

Lipid absorption defects in intestine-specific microsomal triglyceride transfer protein and ATP-binding cassette transporter A1-deficient mice. Iqbal J, Parks JS, Hussain MM.. J Biol Chem. 2013;288(42):30432-44.

Mechanism of the low cholesterol esterification rate in human interstitial fluid (peripheral lymph) [abstract]. Miller NE, Nanjee N, Parks JS, Olszewski WL.. Circulation. 2013;128(22 Suppl):A13029.

Overexpression of apoM in liver stimulates formation of larger, apoM/S1P-enriched plasma HDL [abstract]. Liu MX, Seo JM, Allegood J, Bi X, Zhu XW, Boudyguina E, Gebre AK, Sorci-Thomas M, Thomas MS, Shelness GS, Spiegel S, Parks JS.. Circulation. 2013;128(22 Suppl):A19183.

Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice. Forrest LM, Boudyguina E, Wilson MD, Parks JS.. Atherosclerosis. 2012;220(1):118-121.

CGI-58/ABHD5-derived signaling lipids regulates systemic inflammation and insulin action. Lord CC, Betters JL, Ivanova PT, Milne SB, Myers DS. Madenspacher J, Thomas G, Chung S, Liu M, Davis MA, Lee RG, Crooke RM, Graham MJ, Parks JS, Brasaemle DL, Fessler MB, Brown HA, Brown JM.. Diabetes. 2012;61(2):355-363.

Hepatic ABCA1 and VLDL triglyceride production. Liu M, Chung S, Shelness GS, Parks JS.. Biochim Biophys Acta. 2012;1821(5):770-777.

Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis. Rong S, Cao Q, Liu M, Seo J, Jia L, Boudyguina E, Gebre AK, Colvin PL, Smith TL, Murphy RC, Mishra N, Parks JS.. J Lipid Res. 2012;53(4):686-695.

Hepatic ABC transporters and triglyceride metabolism. Parks JS, Chung S, Shelness GS.. Curr Opin Lipidol. 2012;23(3):196-200.

The NLRP3 inflammasome promotes age-related thymic demise and immunosenescence. Youm Y-H, Kanneganti T-D, Vandanmagsar B, Zhu X, Ravussin A, Adijiang A, Owen JS, Thomas MJ, Francis J, Parks JS, Dixit VD.. Cell Rep. 2012;1(1):56-68.

Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers. Sorci-Thomas MG, Owen JS, Fulp B, Bhat S, Zhu X, Parks JS, Shah D, Jerome WG, Gerelus M, Zabalawi M, Thomas MJ.. J Lipid Res. 2012;53(9):1890-1909.

New roles of HDL in inflammation and hematopoiesis. Zhu X, Parks JS.. Annu Rev Nutr. 2012;32():161-182.

Omega-3 fatty acids ameliorate atherosclerosis by favorably altering monocyte subsets and limiting monocyte recruitment to aortic lesions. Brown AL, Zhu X, Rong S, Shewale S, Seo J, Boudyguina E, Gebre AK, Alexander-Miller MA, Parks JS.. Arterioscler Thromb Vasc Biol. 2012;32(9):2122-2130.

ATP-binding cassette transporter G1 intrinsically regulates invariant NKT cell development. Sag D, Wingender G, Nowyhed H, Wu R, Gebre AK, Parks JS, Kronenberg M, Hedrick CC.. J Immunol. 2012;189(11):5129-5138.

Myeloid cell-specific ABCA1 deletion protects mice from bacterial infection. Zhu X, Westcott MM, Bi X, Liu M, Gowdy KM, Seo J, Cao Q, Gebre AK, Fessler MB, Hiltbold EM, Parks JS.. Circ Res. 2012;111(11):1398-1409.

Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling. Fessler MB, Parks JS.. J Immunol. 2011;187(4):1529-1535.

The effect of ACACB cis-variants on gene expression and metabolic traits. Ma L, Mondal AK, Murea M, Sharma NK, Langberg KA, Das SK, Antinozzi PA, Parks JS, Elbein SC [deceased], Freedman BI, et al.. PLoS ONE. 2011;6(8):e23860.

Adipose tissue ATP binding cassette transporter A1 contributes to high-density lipoprotein biogenesis in vivo. Chung S, Sawyer JK, Gebre AK, Maeda N, Parks JS.. Circulation. 2011;124(15):1663-1672.

Apolipoprotein L1 (APOL1) nephropathy risk variants associate with HDL subfraction concentration in African Americans [abstract]. Freedman BI, Langefeld CD, Murea M, Ma L, Otvos JD, Turner J, Antinozzi PA, Rocco MV, Parks JS.. J Am Soc Nephrol. 2011;22(Abstract Suppl):178A.

Apolipoprotein L1 nephropathy risk variants associate with HDL subfraction concentration in African Americans. Freedman BI, Langefeld CD, Murea M, Ma L, Otvos JD, Turner J, Antinozzi PA, Divers J, Hicks PJ, Bowden DW, Rocco MV, Parks JS.. Nephrol Dial Transplant. 2011;26(11):3805-3810.

ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. Armstrong AJ, Gebre AK, Parks JS, Hedrick CC.. J Immunol. 2010;184(1):173-183.

Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis. Brown JM, Chung S, Sawyer JK, Degirolamo C, Alger HM, Zhu X, Brown AL, Shah R, Davis MA, Kelley K, Wilson MD, Parks JS, Rudell LL, et al.. Arterioscler Thromb Vasc Biol. 2010;30(1):24-30.

Apolipoprotein M expression increases the size of nascent pre beta HDL formed by ATP binding cassette transporter A1. Mulya A, Seo J, Brown AL, Gebre AK, Boudyguina E, Shelness GS, Parks JS.. J Lipid Res. 2010;51(3):514-524.

All Publications

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

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

John S. Parks, Ph.D.

John S. Parks, Ph.D.

Section Chief, Molecular Medicine
Professor, Molecular Medicine
Office of Women in Medicine and Science
Center on Diabetes, Obesity, and Metabolism

Contact Information

Academic: 336-716-2145 | Department: 336-716-2145

Email: jparks@wakehealth.edu

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 hepatosteatosis (i.e., fatty liver). 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 (HL119962)

ATP binding cassette transporter A1 (ABCA1) effluxes phospholipid and free cholesterol from cells, forming nascent high density lipoproteins (HDLs). Because ABCA1 is variably expressed in most cells, we generated hepatocyte-specific ABCA1 KO (HSKO) mice to study the role of hepatocyte ABCA1 in lipid mobilization, transport, and metabolism. Our previous studies showed that hepatocyte ABCA1 regulates the production and catabolism of all three major plasma lipoprotein classes (VLDL, LDL and HDL) that affect coronary heart disease development. In preliminary studies, we found that hepatocyte ABCA1 also reguates hepatic insulin and inflammatory signaling, suggesting the function of hepatocyte ABCA1, while not fully elucidated, is more complex than facilitating bulk cellular cholesterol export and nascent HDL formation. The goal of this project is to determine the role of hepatocyte ABCA1 in lipid mobilization and transport in HSKO mice and humans. In specific aim 1, we are examining the role of hepatocyte ABCA1 expression in hepatic insulin signaling, inflammation, and lipogenesis. Metabolic phenotype, plasma VLDL metabolism, hepatic lipid synthesis, hepatic insulin receptor signaling, and hepatic plasma membrane lipid composition are being determined in chow and high fat-fed wild type and HSKO mice. In specific aim 2, the role of hepatic ABCA1 expression on cholesterol flux from plasma HDL to feces will be examined. We are investigating the plasma decay, hepatic uptake, re-secretion into plasma, and biliary and fecal excretion of HDL FC and CE, relative to apoA-I, in HSKO vs. WT mice. In specific aim 3, the extent to which dietary polyunsaturated (poly) fat, relative to saturated (sat) and monounsaturated (mono) fat, reduces ABCA1 expression in human liver, intestine and adipose tissue will be explored. Interrelationships among tissue ABCA1 RNA and protein expression, plasma HDL cholesterol concentration, particle number and size, and plasma HDL FC efflux capacity as a function of dietary fat saturation will be determined. In specific aim 4, we will determine whether rare coding ABCA1 sequence variants unique to African Americans (AA) (absent in European Americans, EA) affect lipid efflux as well as plasma HDL cholesterol concentration, particle number and size, and plasma HDL efflux potential. Associations between these measurements and coronary artery calcified plaque score, a measure of CHD, will be examined.

The Role of ApoA-IV in Hepatic Lipid Mobilization (HL119983)

An emerging trend suggests that apoB lipoprotein particle number, and not LDL cholesterol, may best predict susceptibility to atherosclerotic cardiovascular disease. As very low density lipoprotein (VLDL) particle size is heterogeneous, reflecting the elasticity of the apoB lipoprotein assembly process, an unanswered question with relevance to many aspects of the metabolic syndrome is how the hepatocyte integrates particle number with particle size to achieve a given rate of hepatic lipid efflux. We are exploring the hypothesis that apolipoprotein A-IV (apoA-IV) is acutely regulated and serves an important role in hepatic lipid efflux by promoting nascent VLDL particle expansion. Defining this previously unknown role of apoA-IV in hepatic lipid metabolism and understanding the mechanism by which it functions has important translational potential, as it is likely that if VLDL-mediated lipid efflux could be achieved by a process of particle expansion at the expense of particle number, a less atherogenic lipoprotein profile may result, while still protecting the liver from steatosis. To explore and validate this hypothesis, three specific aims are being conducted. Aim 1 will define the physiologic and pathophysiologic settings that regulate apoA-IV expression in liver and will establish whether it is hepatic triglyceride (TG) accumulation that induces apoA-IV expression or whether the regulation of apoA-IV is linked to processes associated with enhanced assembly and secretion of VLDL. Aim 2 will establish the impact of apoA-IV on TG secretion and hepatic lipid content and pathophysiology. These studies are supported by preliminary data demonstrating that overexpression of apoA-IV in mouse liver both dramatically induces TG secretion, reducing hepatic lipid burden. Finally, Aim 3 will focus on the mechanism by which apoA-IV promotes TG secretion and will explore the hypothesis that a direct apoA-IV-apoB interaction alters the trafficking kinetics of apoB and promotes greater incorporation of lipid into nascent VLDL particles, while reducing total VLDL particle production.

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