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

Toxicity and chemical composition of commercial road palliatives versus oil and gas produced waters
Environmental Pollution, Farnan, James, Vanden Heuvel, John P., Dorman, Frank L., Warner, Nathaniel R., Burgos, William D., 2023

Preclinical Demonstration of a Novel Treatment with High Efficacy and No Detectable Toxicity for Inflammatory Skin Conditions including Psoriasis
BioMed Research International, Vanden Heuvel, John P., Zhou, Shuling, Patel, Anisha B., Kamerow, Harry N., Baran, Peter, Ford, John P., 2023

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, Xiong, Boya, Weggler, Benedikt, Murrell, Kyra, Dorman, Jr., Franklin Lewis, Dorman, F, Vanden Heuvel, John P., Burgos, William, 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: Systematic identification of genomic markers of drug sensitivity in cancer cells
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

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