Jack (John) P. Vanden Heuvel, PhD

Jack (John) P. Vanden Heuvel, PhD

  • Professor of Molecular Toxicology
  • Pharmacology & Toxicology Undergraduate Program Coordinator
122 Agricultural Science Building
University Park, PA 16802

Areas of Expertise

  • Pharmacology and Toxicology
  • Nuclear receptors
  • Molecular Nutrition
  • Drug Discovery
  • Entrepreneurship and Innovation

Education

  • Postdoctoral training in molecular toxicology, National Institute of Environmental Health Sciences
  • PhD, Environmental Toxicology, University of Wisconsin
  • BS, Pharmacology and Toxicology, University of Wisconsin

Teaching Interests

Biochemical and molecular toxicology, pharmacology, carcinogenesis.

Graduate Programs

  • Molecular Cellular Integrative Biosciences (MCIBS)

Research

Members of the NR superfamily act as intracellular transcription factors that directly regulate gene expression in response to lipophilic molecules. They affect a wide variety of functions, including fatty acid metabolism, reproductive development, and detoxification of foreign substances. To date, over 300 NRs have been cloned, many with unknown endogenous ligands (orphan receptors). Phylogenic analysis has shown six subfamilies (NR1-6) with various groups and individual genes. Several NRs have evolved to respond to dietary lipids and include the fatty acid receptors PPAR, LXR, RXR and FXR. The receptors we have focused on may be considered constituents of a large group of NRs, the “metabolic nuclear receptors” which act as overall sensors of metabolic intermediates, xenobiotics and compounds in the diet and allow cells to respond to environmental changes by inducing the appropriate metabolic genes and pathways. Most NRs regulate gene expression in predominantly the same fashion. Prior to activation, NRs often exist in multiprotein complexes that vary depending on the family of receptor under question. When a ligand binds to its cognate receptor, a conformational change occurs (“activation”) that changes the protein- protein interfaces of the molecule. As a result, the activated receptor interacts with a NR response element (NRE) within the regulatory region of a target gene; upon recruitment of various transcriptional coactivators and subsequently RNA polymerase II (polII), initiation of transcription of the target gene occurs.

Our laboratory focused on the three likely candidates for NRs that respond to dietary fatty acids, PPAR, RXR and LXR. In particular the peroxisome proliferator-activated receptors (PPARs; PPARα, β/δ and γ) are of particular interest as they serve key roles in toxicology, carcinogenesis and nutrition. We study the ligands of these receptors, the genes they affect and the physiological consequences of their activation.

Publications

Detection and removal of biologically active organic micropollutants from hospital wastewater
Science of the Total Environment, Castillo Meza, Luis, Piotrowski, Paulina, Farnan, James, Tasker, Travis L., Xiong, Boya, Weggler, Benedikt, Murrell, Kyra, Dorman, Frank L., Vanden Heuvel, John P., Burgos, William D., 2020

Diets low in saturated fat with different unsaturated fatty acid profiles similarly increase serum-mediated cholesterol efflux from THP-1 macrophages in a population with or at risk for metabolic syndrome
Journal of Nutrition, Liu, Xiaoran, Garban, Josephine, Jones, Peter J., Vanden Heuvel, John Patrick, Lamarche, Benoît, Jenkins, David J., Connelly, Philip W., Couture, Patrick, Pu, Shuaihua, Fleming, Jennifer Anne, West, Sheila Grace, Kris-Etherton, Penny Margaret, 2018

Replication study
eLife, Vanden Heuvel, John P., Maddox, Ewa, Maalouf, Samar W., Iorns, Elizabeth, Tsui, Rachel, Denis, Alexandria, Perfito, Nicole, Errington, Timothy M., 2018

Effects of cranberry extracts on gene expression in THP-1 cells
Food Science and Nutrition, Hannon, Daniel B., Thompson, Jerry T., Khoo, Christina, Juturu, Vijaya, Vanden Heuvel, John P., 2017

Therapeutic potential of GW501516 and the role of Peroxisome proliferator-activated receptor β/δ and B-cell lymphoma 6 in inflammatory signaling in human pancreatic cancer cells
Biochemistry and Biophysics Reports, Smith, Russell W., Coleman, Jeffrey D., Thompson, Jerry T., Vanden Heuvel, John Patrick, 2016

Biliverdin reductase A attenuates hepatic steatosis by inhibition of Glycogen Synthase Kinase (GSK) 3β phosphorylation of serine 73 of Peroxisome Proliferator-activated Receptor (PPAR) α
Journal of Biological Chemistry, Hinds, Terry D., Burns, Katherine A., Hosick, Peter A., McBeth, Lucien, Nestor-Kalinoski, Andrea, Drummond, Heather A., Alamodi, Abdulhadi A., Hankins, Michael W., Vanden Heuvel, John P., Stec, David E., 2016

Registered report
eLife, Vanden Heuvel, John P., Bullenkamp, Jessica, Iorns, Elizabeth, Gunn, William, Tan, Fraser, Lomax, Joelle, Perfito, Nicole, Errington, Timothy, 2016

Effects of cranberry extracts on gene expression in THP-1 cells.
Food science & nutrition, Hannon, D, Thompson, Jerry, Khoo, C, Juturu, V, Vanden Heuvel, John, 2016

Differential nucleobase protection against 5-fluorouracil toxicity for squamous and columnar cells: Implication for tissue function and oncogenesis
Investigational New Drugs, Vanden Heuvel, John Patrick, Thompson, Jerry T., Albrecht, Prajakta, Mandetta, Donald, Kamerow, Harry, Ford, John P., 2015

Effects of whole and refined grains in a weight-loss diet on markers of metabolic syndrome in individuals with increased waist circumference
American Journal of Clinical Nutrition, Jackson, Kristina Harris, West, Sheila G., Vanden Heuvel, John P., Jonnalagadda, Satya S., Ross, Alastair B., Hill, Alison M., Grieger, Jessica A., Lemieux, Susan K., Kris-Etherton, Penny M., 2014

Comment on "associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans" by Fletcher et al., Environ Int.57-59, (2013) 2-10
Environment International, Vanden Heuvel, John, 2013

Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors
Toxicology in Vitro, Paul, Katie B., Thompson, Jerry T., Simmons, Steven O., Vanden Heuvel, John Patrick, Crofton, Kevin M., 2013

Role of peroxisome proliferator-activated receptor β/δ and B-cell lymphoma-6 in regulation of genes involved in metastasis and migration in pancreatic cancer cells
PPAR Research, Coleman, Jeffrey D., Thompson, Jerry T., Smith, Russell W., Prokopczyk, Bogdan, Vanden Heuvel, John P., 2013

Marine- and plant-derived omega-3 fatty acids differentially regulate prostate cancer cell proliferation.
Molecular and clinical oncology, Eser, P, Vanden Heuvel, John, Araujo, J, Thompson, Jerry, 2013

The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2 dependent PGF synthesis in adipocytes
Prostaglandins and Other Lipid Mediators, Belda, Benjamin J., Thompson, Jerry T., Sinha, Raghu, Prabhu, K. Sandeep, Heuvel, John P.Vanden, 2012

Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids
Progress in Molecular Biology and Translational Science, Vanden Heuvel, John P., 2012

10E12Z CLA alters adipocyte differentiation and adipocyte cytokine expression and induces macrophage proliferation
Journal of Nutritional Biochemistry, Belda, Benjamin J., Thompson, Jerry T., Eser, Pinar O., Vanden Heuvel, John P., 2012

Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression
Journal of Nutritional Biochemistry, Zhang, Jun, Kris-Etherton, Penny M., Thompson, Jerry T., Hannon, Daniel B., Gillies, Peter J., Vanden Heuvel, John P., 2012

Δ 12-prostaglandin J 3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice
Blood, Hegde, Shailaja, Kaushal, Naveen, Ravindra, Kodihalli C., Chiaro, Christopher, Hafer, Kelsey T., Gandhi, Ujjawal H., Thompson, Jerry T., Vanden Heuvel, John Patrick, Kennett, Mary J., Giblin, Pamela Hankey, Paulson, Robert, Prabhu, Kumble Sandeep, 2011

Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA desaturase 1 in THP-1 macrophage-derived foam cells
Nutrition and Metabolism, Zhang, Jun, Grieger, Jessica A., Kris-Etherton, Penny Margaret, Thompson, Jerry T., Gillies, Peter J., Fleming, Jennifer Anne, Vanden Heuvel, John Patrick, 2011

The Effects of Tamoxifen and Fish Oil on Mammary Carcinogenesis in Polyoma Middle T Transgenic Mice
Hormones and Cancer, Manni, Andrea, Xu, Haifang, Washington, Sharlene, Aliaga, Cesar, Das, Arunangshu, Cooper, Timothy, Richie, John P., Prokopczyk, Bogdan, Calcagnotto, Ana, Trushin, Neil, Van den Heuvel, John P., Hamilton, Christopher, Demers, Laurence M., Liao, Jason, Verderame, Michael F., El-Bayoumy, Karam, 2011

A high antioxidant spice blend attenuates postprandial insulin and triglyceride responses and increases some plasma measures of antioxidant activity in healthy, overweight men.
The Journal of nutrition, Skulas-Ray, Ann, Kris-Etherton, Penny, Teeter, D, Chen, Chuanwen, Vanden Heuvel, John, West, Sheila, 2011

15-deoxy-Δ12,14-prostaglandin J2-glycerol ester, a putative metabolite of 2-arachidonyl glycerol, activates peroxisome proliferator activated receptor γ
Molecular pharmacology, Raman, Priyadarshini, Kaplan, Barbara L.F., Thompson, Jerry T., Vanden Heuvel, John P., Kaminski, Norbert E., 2011

Development of a cell-based, high-throughput screening assay for cholesterol efflux using a fluorescent mimic of cholesterol
Assay and Drug Development Technologies, Zhang, Jun, Cai, Sutang, Peterson, Blake R., Kris-Etherton, Penny Margaret, Vanden Heuvel, John Patrick, 2011

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia.
The American journal of clinical nutrition, Skulas-Ray, Ann, Kris-Etherton, Penny, Harris, W, Vanden Heuvel, John, Wagner, P, West, Sheila, 2011

Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression: evidence for a farnesoid-X-receptor mechanism of action
J Nutr Biochem, Zhang, J., Kris-Etherton, P., Thompson, J., Hannon, D., Gillies, P., Vanden Heuvel, John, 2011

Inhibition of macrophage adhesion activity by 9trans,11trans-conjugated linoleic acid
Journal of Nutritional Biochemistry, Lee, Yunkyoung, Vanden Heuvel, John Patrick, 2010

Effect of pistachio oil on gene expression of ifn-induced protein with tetratricopeptide repeats 2
Molecular Nutrition and Food Research, Zhang, Jun, Kris-Etherton, Penny Margaret, Thompson, Jerry T., Vanden Heuvel, John Patrick, 2010