About

Trevor M. Penning, Ph.D., is the Molinoff Professor at the University of Pennsylvania School of Medicine and a member of the Abramson Cancer Center. He serves as the Director of the Center of Excellence in Environmental Toxicology and is involved in multiple leadership roles including Co-Leader of the Tobacco and Environmental Carcinogenesis Program and Director of the Certificate Program in Environmental Health Sciences. His research focuses on steroid hormone transforming aldo-keto reductases, particularly within the aldo-keto reductase superfamily, which contains mammalian hydroxysteroid dehydrogenases. These enzymes regulate steroid hormone activity by converting potent hormones into inactive metabolites or vice versa, influencing receptor occupancy and trans-activation, and are considered therapeutic targets. His work includes structure-based inhibitor design targeting enzymes such as AKR1C3, which is involved in intratumoral androgen biosynthesis in castrate resistant prostate cancer, and studies on enzymes like steroid 5beta-reductase (AKR1D1) that play roles in bile-acid biosynthesis. Penning's research employs techniques such as site-directed mutagenesis, x-ray crystallography, kinetics, transfection studies, and siRNA. He has contributed to understanding the metabolic activation of chemical carcinogens by human AKRs, including pathways involving PAHs, nitroarenes, and oil exposure biomarkers. His work also explores the role of AKRs in mutagenesis, carcinogenesis, and steroid metabolism, with implications for cancer and endocrine disorders.

Research topics

• Biology
• Chemistry
• Artificial Intelligence
• Machine Learning
• Computer Science
• Data Mining
• Biochemistry
• Cancer research
• Engineering
• Genetics
• Cell biology
• Medicine
• Pharmacology
• Environmental chemistry
• Biochemical engineering
• Mathematics
• Internal medicine

Selected publications

• Human aldo-keto reductases (AKR1C1-AKR1C3) increase the mutagenicity of environmental nitroarenes in the mammalian HPRT forward gene mutagenicity assay

  Mutation Research/Genetic Toxicology and Environmental Mutagenesis · 2026-04-17

  articleOpen accessSenior authorCorresponding

  The diesel exhaust constituent 1-nitropyrene (1-NP) is classified as a probable human carcinogen and other constituents 1,8-dinitropyrene (1,8-DNP) and 3-nitrobenzanthrone (3-NBA) are classified as possible human carcinogens by the International Agency for Research on Cancer. These nitroarenes are activated by nitroreduction via nitroso- and hydroxylamino- intermediates on route to the corresponding amine product(s). Two types of DNA adduct can occur in this sequence. First, the hydroxylamino- intermediate can undergo sulphonation or acetylation giving rise to a strong leaving group so that stable covalent adducts can form. Second, back oxidation of these air sensitive intermediates can give rise to reactive oxygen species and nitrogen species (ROS, RNS) so that oxidatively damaged bases can form. Human aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 play prominent roles in the nitroreduction of these nitroarenes in human lung cell lines. We now report that when AKR1C1-AKR1C3 are transfected into V79-4 cells we observe a significant increase in HPRT gene mutation. The mutation is dependent on AKR1C enzyme activity since isoform specific inhibitors reduced the number of mutant colonies formed. ROS scavengers reduced the number of mutant colonies formed with 1-NP, 1-8-DNP and 3-NBA in the presence of transfected AKR1C1. Ethyl gallate and the superoxide dismutase mimetic (MnTBAP) reduced the number of mutant colonies formed. Nitric oxide scavengers, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1 H -imidazoyl-1-oxy-3-oxide and uric acid, also reduced the number of mutant colonies formed. Our results suggest that both 8-oxo-dG and 8-nitro-dG lesions may contribute to the mutation observed. Since AKR1C1-AKR1C3 are potently induced by NRF2, its activation might increase the mutagenicity of nitroarenes in the context of diesel exhaust exposure. • Human aldo-keto reductases (AKR) increase the mutagenicity of nitroarenes at the HPRT locus • The mutation is dependent on AKR1C enzyme activity since AKR inhibitors reduce the mutant colonies • ROS and RNS scavengers attenuate the mutant colonies suggesting 8-oxo-dG and 8-nitro-dG contribute to mutation • NRF2 activation induces AKR1C enzymes raising the possibility that this could increase the mutagenicity of nitroarenes

  PublisherDOI

• Update to RIFM fragrance ingredient safety assessment, 1,1-diethoxyisooctane, CAS Registry Number 69178-43-4

  Food and Chemical Toxicology · 2025-05-09

  article
  PublisherDOI

• RIFM fragrance ingredient safety assessment, cedrene, CAS Registry Number 11028-42-5

  Food and Chemical Toxicology · 2025-11-08

  review
  PublisherDOI

• Frontiers in steroid research: Steroid congress 2023

  The Journal of Steroid Biochemistry and Molecular Biology · 2025-06-06

  editorial1st authorCorresponding
  PublisherDOI

• Advancing chemical grouping: development and application of signature-based structure-activity groups for non-animal safety assessments

  Computational Toxicology · 2025-11-13

  article
  PublisherDOI

• RIFM fragrance ingredient safety assessment, 1-octanol, CAS registry number 111-87-5

  Food and Chemical Toxicology · 2025-04-18 · 1 citations

  review
  PublisherDOI

• Update to RIFM fragrance ingredient safety assessment, hydroxycitronellal dimethyl acetal, CAS Registry number 141-92-4

  Food and Chemical Toxicology · 2025-05-09 · 1 citations

  review
  PublisherDOI

• Update to RIFM fragrance ingredient safety assessment, amyl hexanoate, CAS registry number 540-07-8

  Food and Chemical Toxicology · 2025-04-17

  articleOpen access

  • Amyl hexanoate ; a safety assessment based on RIFM's criteria. • A safety assessment based on 7 human health endpoints plus environmental. • All endpoints were cleared using target data, read-across, and/or TTC.

  PublisherDOI

• Update to RIFM fragrance ingredient safety assessment, fenchone, CAS Registry Number 1195-79-5

  Food and Chemical Toxicology · 2025-05-21

  article
  PublisherDOI

• Update to RIFM fragrance ingredient safety assessment, isophytol, CAS Registry Number 505-32-8

  Food and Chemical Toxicology · 2025-05-05

  article
  PublisherDOI

Recent grants

• Translational Research Training Program in Environmental Health Sciences

  NIH · $5.3M · 2012–2027

• NIH Grant R01ES015857

  NIH · $2.2M · 2013

• Environmental Health Informatics Core

  NIH · $16.5M · 2006–2030

• NIH Grant R01CA055711

  NIH · $1.7M · 2001

• NIH Grant R01CA039504

  NIH · $6.2M · 2014

Frequent coauthors

• M. Bruze

  Lund University

  1421 shared

• A.M. Api

  Research Institute for Fragrance Materials

  1418 shared

• D. Belsito

  Columbia University Irving Medical Center

  1417 shared

• A. Lapczynski

  Research Institute for Fragrance Materials

  1416 shared

• W. Dekant

  University of Würzburg

  1416 shared

• G. Ritacco

  Universidade de São Paulo

  1415 shared

• Y. Thakkar

  Research Institute for Fragrance Materials

  1408 shared

• C. Deodhar

  Research Institute for Fragrance Materials

  1407 shared

Labs

• Systems Pharmacology and Translational TherapeuticsPI

Education

• Postdoctoral Fellowship, Pharmacology & Experimental Therapeutics

  Johns Hopkins University

  1982

• PhD/Biochemistry, Physiology & Biochemistry

  University of Southampton

  1976

• BSc/Physiology & Biochemistry, Physiology & Biochemistry

  University of Southampton

  1972

Awards & honors

• Molinoff Professor
• Member, Abramson Cancer Center
• Director Center of Excellence in Environmental Toxicology, U…
• Co-Leader, Tobacco and Environmental Carcinogenesis Program,…
• Director Certificate Program in Environmental Health Science…