Senior Research Chemist — Division of Biochemical Toxicology

Peter Fu, Ph.D.
(870) 543-7121
[email protected]  

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FDA Lifetime Achievement Award Recipient

Peter P. Fu, Ph.D., a senior research chemist in NCTR’s Division of Biochemical Toxicology was selected for the 2018 FDA Scientific Lifetime Achievement Award for “elucidating the biological effects and mechanisms of action of carcinogens and other toxic constituents of foods, drugs, and cosmetic products regulated by the FDA.”

• Dr. Fu began his career at NCTR almost 40 years ago after receiving a Ph.D. from the University of Illinois at Chicago and working at Ben May Institute for Cancer Research at the University of Chicago. Recruited to NCTR in 1979, Dr. Fu has supported NCTR’s mission to provide research for the regulatory needs of FDA product centers; focusing on mechanistic studies of the genotoxicity and tumorigenicity of pyrrolizidine alkaloids, nanomaterials, and herbal dietary supplements. In addition to this most recent prestigious award, he has previously been awarded the FDA Commendable Service Award and the FDA Award of Merit, along with the Public Health Service Special Recognition Award. Recognized internationally as an expert in chemical carcinogenesis, Dr. Fu's 446 publications encompass seminal studies concerning polycyclic aromatic hydrocarbons, nitroaromatic compounds, and pyrrolizidine alkaloids. His studies have greatly impacted the public-health decisions made by FDA, NIEHS/National Toxicology Program, International Agency for Research on Cancer, and the United Nations Food and Agricultural Organization.Dr. Fu believes his two most significant contributions to science through the years are:
  1. establishing the newborn mouse assay in a regulatory setting, as a complementary or replacement assay for the standard two‐year rodent cancer bioassay, and
  2. results from his research on mechanistic determination on pyrrolizidine alkaloids that have been used by agencies worldwide to describe the risks associated with exposure to this class of chemicals.

Background

Dr. Peter Fu has conducted research in the field of chemical carcinogenesis for 43 years. He received a Ph.D. from University of Illinois at Chicago in 1973 and worked at the Ben May Institute for Cancer Research at the University of Chicago from 1973 to 1979, where he focused his research on chemical carcinogenesis. Dr. Fu was recruited to NCTR in 1979. In support of NCTR’s mission to provide research for the regulatory needs of FDA product centers, his research has focused on mechanistic studies of the genotoxicity and tumorigenicity of pyrrolizidine alkaloids, nanomaterials, and herbal dietary supplements. In March 1997, he was appointed to the Senior Biomedical Research Service. Dr. Fu has served as an adjunct professor at several universities in the United States and China. He has also worked with the following science journals:

Journal of Environmental Science and Health, Part C
Editor
2001 – Present

Journal of Food and Drug Analysis
Editor
2013 – Present

BioMedical Research International
Editorial board member
2013 – Present

Toxicology and Industry Health
Editorial board member
2003 – Present

Frontiers in Ethnopharmacology
Editorial board member
2011 – Present

Research Interests

Dr. Fu’s research interests include chemical carcinogenesis of pyrrolizidine alkaloids, polycyclic aromatic hydrocarbons (PAHs), and nitro-PAHs as well as structure activity relationships, DNA adducts as biomarkers, herbal dietary supplements, and nanotoxicology. Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. Many pyrrolizidine alkaloids are hepatotoxic and tumorigenic and represent a threat to human health and safety. Regulatory agencies worldwide have issued bans and alerts on products containing pyrrolizidine alkaloids. To date, however, there are no practical analytical methods to quantify the total toxic pyrrolizidine alkaloid content present in herbal plants and products, or in foods, such as herbal dietary supplements, honey, and milk. Therefore, mechanism-based analytical methods must be developed to assess the risk posed by pyrrolizidine alkaloids in herbal plants and herbal products. Dr. Fu’s current research focuses on the quantitation of pyrrolizidine alkaloid-DNA adducts and pyrrolizidine alkaloid-protein adducts as mechanism-based methods for this need. Dr. Fu’s mechanistic studies determined that different types of tumorigenic-pyrrolizidine alkaloids exert tumorigenicity through a common metabolic-activation pathway. These findings are highly significant and strongly imply that a common metabolic mechanism is involved. Furthermore, the consistent type of DNA damage produced correlated with the biological effects of pyrrolizidine alkaloids. Dr. Fu proposes that, upon metabolism of the herbal products in vivo, in vitro, or in the cultured cells, quantitation of the level of the DHP-DNA adducts should be an assessable, reliable, and mechanism-based bioassay. Dr. Fu has also developed an LC/MS analytical method to quantify blood DHP-protein adducts as a noninvasive biomarker of pyrrolizidine alkaloid tumorigenicity and exposure. The levels of DHP-protein adducts in the blood correlated well with the levels of DHP-DNA adducts in the liver. This LC/MS/MS analytical method has the potential to be used for assessing human exposures to pyrrolizidine alkaloids.

Professional Societies/National and International Groups

National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
Scientific Advisor
2012 – Present

Selected Publications

Pyrrolizidine Alkaloids Derived DHP-DNA Adducts are a Common Biological Biomarker of Pyrrolizidine Alkaloid-Initiated Tumorigenicity.
Xia Q., Zhao Y., Von Tungeln L., Doerge D., Lin G., Cai L., and Fu P.   
Chem Res Toxicol. 2013, 26, 1384-1396. 

Mechanism of Nanotoxicity - Generation of Reactive Oxygen Species.
Fu P., Xia Q., Hwang H., Ray P., and Yu H. 
J Food Drug Anal. 2014, 22, 64-75. 

Enzyme-Like Activity of Nanomaterials.
He X., Wamer W., Xia Q., Yin J., and Fu P.    
Environ Sci Health Part C. 2014, 32, 186-211. 

Metabolic Activation of Pyrrolizidine Alkaloids: Insights into the Structural and Enzymatic Basis.
Ruan J., Yang M., Fu P., and Lin G.
Chem Res Toxicol. 2014, 27, 1030-1039.  

Reaction of Dehydropyrrolizidine Alkaloids with Valine and Hemoglobin.
Zhao Y., Wang S., Xia Q., Gamboa da Costa G., Doerge D., Cai L., and Fu P.
Chem Res Toxicol. 2014, 27, 1720-1731. 

Metabolic Activation of Pyrrolizidine Alkaloids Leading to Phototoxicity and Photogenotoxicity in Human HaCaT Keratonicytes. 
Wang C., Xia Q., Li M., Wang S., Zhao Y., Tolleson W., Yin J., and Fu P.
J Environ Sci Health Part C. 2014, 32, 362-384. 

UVA Photoirradiation of Benzo[a]pyrene Metabolites – Induction of Cytotoxicity, Rective Oxygen Species, and Lipid Peroxidation. 
Xia Q., Chiang H., Yin J., Cheng S., Cai L., Yu H., and Fu P. 
Toxicol Ind Health. 2015, 31, 898-910. 

7-Glutathione Pyrrole Adduct - A Potential DNA Reactive Metabolite of Pyrrolizidine Alkaloids.
Xia Q., Ma L., He X., Cai L., and Fu P.
Chem ResToxicol. 2015, 28, 615-620. 

Pyrrolizidine Alkaloids: Toxic Phytochemicals Found in Food.
Fu P. and Xia Q.
Food Poisoning: Outbreaks, Bacterial Sources and Adverse Health Effects. Paresh C. Ray (editor), Nova Science Publishers, Hauppauge, New York, 2015, 1-33. 

Absolute Configuration, Stability, and Interconversion of 6,7-Dihydro-7-Hydroxy-1-Hydroxymethyl-5H- Pyrrolizine Valine Adducts and Their Phenylthiohydantoin Derivatives.
Jiang X., Wang S., Zhao Y., Xia Q., Cai L., Sun Y., and Fu P.
J Food Drug Analy. 2015, 23, 318-326.  

Toxicity of Engineered Metal Oxide Nanomaterials by Nano-Bio-Eco Interactions: A Review and Perspective.
He X., Aker W., Fu P., and Hwang H.
Environ Sci Nano. 2015 2, 564-582.  

Platinum Nanoparticles: Efficient and Stable Catechol Oxidase Mimetics.
Liu Y., Wu H., Chong Y., Wamer W., Xia Q., Cai L., Nie Z., Fu P., and Yin J.
ACS Appl Mater Inter. 2015, 7, 19709-19717. 

Synthesis and Phototoxicity of Isomeric 7,9-Diglutathione Pyrrole Adducts: Formation of Reactive Oxygen Species and Induction of Lipid Peroxidation.
Ma L., Zhao H., Xia Q., Cai L., and Fu P.
J Food Drug Anal. 2015, 23, 577-586. 

Blood Pyrrole-Protein Adducts – A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans.
Ruan J., Gao H., Na L., Xue J., Chen J., Ke C., Ye Y., Fu P., Zheng J., Wang J., and Lin G.
J Environ Sci Health Part C. 2015, 33, 404-421. 

A Novel Ultra-Performance Liquid Chromatography Hyphenated with Quadrupole Time of Flight Mass Spectrometry Method for Rapid Estimation of Total Toxic Retronecine-Type of Pyrrolizidine Alkaloids in Herbs Without Requiring Corresponding Standards.
Zhu L., Ruan J., Li N., Fu P., Ye Y., and Lin G. 
Food Chem. 2016, 194, 1320-1328. 

Cytotoxicity of Pyrrolizidine Alkaloid in Human Hepatic Parenchymal and Sinusoidal Endothelial Cells: Firm Evidence for the Reactive Metabolites of Pyrrolizidine Alkaloid-Induced Hepatotoxicity.
Yang M., Ruan J., Fu P., and Lin G.
Chem-Biol Interact. 2016, 243, 119-126. 

7-Cysteine-Pyrrole Conjugate - A New Potential DNA Reactive Metabolite of Pyrrolizidine Alkaloids.
He X., Xia Q., Ma L., Cai L., and Fu P.
J Environ Sci Health Part C. 2016 34, 57-76. 

Food Chemical Carcinogens: Sources and Mechanisms of Exogenous DNA Adduct Formation.
Fu P. and Xia Q. 
Food Chemical Carcinogens. Debasis Bagchi (ed.) Taylor & Francis Publisher. 2016, 57-81. 

The Long Persistence of Pyrrolizidine Alkaloid-Derived DNA Adducts In Vivo: Kinetic Study Following Single and Multiple Exposures in Male ICR Mice.
Zhu L., Xue J., Xia Q., Fu P., and Lin G.
Archives of Toxicology. 2016, doi:10.1007/s00204_016-1713-z 

Pyrrolizidine Alkaloid-Protein Adducts - Potential Non-Invasive Biomarkers of Pyrrolizidine Alkaloid-Initiated Liver Toxicity and Exposure.
Xia Q., Zhao Y., Lin G., Beland F., Cai L., and Fu P. 
Chem Res Toxicol. 2016, 29 1282-1292.
 

Lab Members

Contact information for all lab members:
(870) 543-7121
[email protected]

Xiaobo He
Postdoctoral Fellow

Qingsu Xia, M.D.
Biologist