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

Lipoxygenase catalyzed metabolites derived from docosahexaenoic acid are promising antitumor agents against breast cancer
Scientific Reports, Chen, Kun Ming, Thompson, Henry, Vanden-Heuvel, John P., Sun, Yuan Wan, Trushin, Neil, Aliaga, Cesar, Gowda, Krishne, Amin, Shantu, Stanley, Bruce, Manni, Andrea, El-Bayoumy, Karam, 2021

Accumulating evidence to support the safe and efficacious use of a proprietary blend of capsaicinoids in mediating risk factors for obesity
Food Science and Nutrition, Mariwala, Javahar Kohli, Rai, Deshanie, Padigaru, Muralidhara, Ashok Morde, Abhijeet, Maddox, Ewa, Maalouf, Samar, Smith, Kayla, Vanden Heuvel, John P., 2021

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, Jr., Franklin Lewis, Vanden Heuvel, John P., Burgos, William D., 2020

Environmental and Human Health Impacts of Spreading Oil and Gas Wastewater on Roads
Environmental Science & Technology, Tasker, T. L., Burgos, W. D., Piotrowski, P., Castillo-Meza, L., Blewett, T. A., Ganow, K. B., Stallworth, A., Delompré, P. L.M., Goss, G. G., Fowler, L. B., Vanden Heuvel, J. P., Dorman, F., Warner, N. R., 2018

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: the canola oil multicenter intervention trial
Journal of Nutrition, Liu, Xiaoran, Garban, Josephine, Jones, Peter J., Heuvel, Jack Vanden, Lamarche, Benoît, Jenkins, David J., Connelly, Philip W., Couture, Patrick, Pu, Shuaihua, Fleming, Jennifer A., West, Sheila G., Kris-Etherton, Penny M., 2018

Replication study: Systematic identification of genomic markers of drug sensitivity in cancer cells
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 P., 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, J, Khoo, C, Juturu, V, Vanden Heuvel, John, 2016

Nutrigenomic approaches to unraveling the physiological effects of complex foods, Gillies, Peter J., Vanden Heuvel, John P., 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 P., 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: A randomized controlled-feeding trial
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

Effects of a DASH-like diet containing lean beef on vascular health
Journal of Human Hypertension, Roussell, M. A., Hill, A. M., Gaugler, T. L., West, S. G., Ulbrecht, J. S., Vanden Heuvel, J. P., Gillies, P. J., Kris-Etherton, P. M., 2014

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 P., 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

Fish oil alters tamoxifen-modulated expression of mRNAs that encode genes related to differentiation, proliferation, metastasis, and immune response in rat mammary tumors
Nutrition and Cancer, Bidinotto, Lucas Tadeu, De Cicco, Ricardo López, Vanegas, Johana Erika, Santucci-Pereira, Julia, Heuvel, John Patrick Vanden, Washington, Sharlene, Aliaga, Cesar, Xu, Haifang, Russo, Irma H., Manni, Andrea, El-Bayoumy, Karam, Russo, Jose, 2012

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

Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil
Journal of Lipid Research, Gillies, Peter J., Bhatia, Sujata K., Belcher, Leigh A., Hannon, Daniel B., Thompson, Jerry T., Vanden Heuvel, John P., 2012

Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks
Journal of the American College of Nutrition, Percival, Susan S., Vanden Heuvel, John P., Nieves, Carmelo J., Montero, Cindy, Migliaccio, Andrew J., Meadors, Joanna, 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
Nutrition Reports International, 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: evidence for a farnesoid-X-receptor mechanism of action
Nutrition Reports International, Zhang, Jun, Kris-Etherton, Penny M., Thompson, Jerry T., Hannon, Daniel B., Gillies, Peter J., Vanden Heuvel, John P., 2012

Mechanistic examination of walnuts in prevention of breast cancer.
Nutrition and Cancer, Heuvel, John P.Vanden, Belda, Benjamin J., Hannon, Dan B., Kris-Etherton, Penny M., Grieger, Jessica A., Zhang, Jun, Thompson, Jerry T., 2012

Beef in an optimal lean diet study: Effects on lipids, lipoproteins, and apolipoproteins
American Journal of Clinical Nutrition, Roussell, Michael A., Hill, Alison M., Gaugler, Trent L., West, Sheila G., Vanden Heuvel, John P., Alaupovic, Petar, Gillies, Peter J., Kris-Etherton, Penny M., 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., Van Den Heuvel, John P., Kennett, Mary J., Hankey, Pamela, Paulson, Robert F., Prabhu, K. Sandeep, 2011

A high antioxidant spice blend attenuates postprandial insulin and triglyceride responses and increases some plasma measures of antioxidant activity in healthy, overweight men.
Journal of Nutrition, Skulas-Ray, Ann C., Kris-Etherton, Penny M., Teeter, Danette L., Chen, C. Y.Oliver, Heuvel, John P.Vanden, West, Sheila G., 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

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 M., Heuvel, John P.Vanden, 2011

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia.
American Journal of Clinical Nutrition, Skulas-Ray, Ann C., Kris-Etherton, Penny M., Harris, William S., Vanden Heuvel, John P., Wagner, Paul R., West, Sheila G., 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 M., Thompson, Jerry T., Gillies, Peter J., Fleming, Jennifer A., Vanden Heuvel, John P., 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

Xenobiotic metabolism, disposition, and regulation by receptors
Toxicological Sciences, Omiecinski, Curtis J., Vanden Heuvel, John P., Perdew, Gary H., Peters, Jeffrey M., 2011