Tom K. Hei, PhD

Profile Headshot

Overview

Dr. Tom Hei has been a faculty of the Department of Radiation Oncology / Center for Radiological Research for the past 38 years and as Vice-Chair for Research in the Department and the Associate Director of the Center for Radiological Research for the past 12 years. His laboratory focuses on elucidating the basic mechanisms of radiation and environmental cancer using both human epithelial cell models as well as genetic-engineered animal models. His lung cancer program has studies related to asbestos fibers, arsenic and radon, seemingly diverse physical and chemical carcinogens that all involve a free radical component. Using a charged particle microbeam, his laboratory has demonstrated unequivocally that radiation induces both extranuclear as well as extracellular effects that set off a paradigm shift in our understanding of the new radiobiology. His laboratory further demonstrated the role of cyclooxygenase-2 as a mediator in the induction of in vivo non-targeted response using a COX2 knockout mouse model. Furthermore, his laboratory has made seminal contributions in understanding the mechanism of radiation carcinogenesis with the identification that the TGFβ1 gene has tumor suppressor function in both lung and breast cancers. In the environmental field, his laboratory was the first to demonstrate that inorganic arsenic and asbestos fibers, previously classified as non-genotoxic carcinogens, are in fact mutagenic and induce mainly multi-locus deletions and that mitochondrial damages are essential in mediating the genotoxic response. Dr. Hei was a panel member of the National Academy of Sciences in reviewing the NIOSH Roadmap for Research on Mineral Fibers as well as being a team leader in writing the report on the genotoxic mechanism of asbestos fibers commissioned by the NIEHS / EPA. He was a team leader of the National Academy of Sciences task force in evaluating the NASA evidence report on space radiation carcinogenesis in 2016. Dr. Hei was elected Educator of the Year by the Association of Residents in Radiation Oncology in 2012 and was the past president of the Radiation Research Society. He has mentored numerous doctoral, medical, residents and postdoctoral fellows over the years, many of whom are now leaders in their own fields around the world.

Academic Appointments

  • Professor of Radiation Oncology
  • Professor of Environmental Health Sciences

Administrative Titles

  • Associate Director, Center for Radiological Research
  • Vice-chairman of Research, Department of Radiation Oncology

Gender

  • Male

Credentials & Experience

Education & Training

  • BSc, 1977 Biology with Chemistry minor, University of Wisconsin-Whitewater
  • PhD, 1983 Experimental Pathology, Case Western Reserve University.

Honors & Awards

  • 2019 President, Radiation Research Foundation
  • 2017 Honorary Doctor of Science (D.Sc) Degree, Amity University.
  • 2017 Distinguished Alumni Award for Professional Achievements, Univ. Wisconsin
  • 2017 President, 5th Inter. Meeting on Space Radiation and Particle Therapy, China
  • 2012 President, Radiation Research Society
  • 2012 Oversea Expert Panel, Chinese Academy of Sciences
  • 2012 Educator of the Year, Association of Residents in Radiation Oncology
  • 2010 Roentgen Lecture, NY Academy of Sciences
  • 2008 Dynamic Achievement Award, organization of Chinese American
  • 2006 Distinguished Visiting Professorship, University of Iowa
  • 2004 Rudbeck Lecturer, University of Uppsala
  • 2002 Distinguished Cancer Center Lecture, University of Kentucky
  • 1999 Keynote Speaker, Environmental Pathology Training Program at Brown University
  • 1999 Keynote Speaker, 7th Intern. Symposium on Fiber Toxicol. Maastricht, Netherlands
  • 1999 Keynote Speaker, 9th National Radon Meeting, Las Vegas, NE
  • 1989 NIH Biological Research Support Grant, Columbia University
  • 1985 NIH Biological Research Support Grant, Columbia University
  • 1976 Summa Cum Laude, University of Wisconsin Board of Regents

Research

Extranuclear effects of ionizing radiation

Ever since X-rays were discovered by Röentgen more than a century ago, it has always been assumed that nucleus, or specifically DNA, as the main target of radiation induced mutation and cancer. As such, generations of students in radiation biology have been taught that such heritable biological effects are the consequence of a direct radiation-nuclear interaction. Using a precision charged particle microbeam, my laboratory showed that targeted cytoplasmic irradiation induced mutation in the nucleus of hit cells and that the type of mutations induced was very different from those generated through direct nuclear irradiation. This initial observation set forth the concept of extranuclear effects of ionizing radiation. Since the original study published in 1999, we have further shown that mitochondria are the ultimate targets and that reactive radical species, coupled with membrane lipid peroxidation and induction of cyclooxygenase 2(COX2), mediated the genotoxic response of targeted cytoplasmic irradiation.

  • Wu, L.J., Randers-Pehrson, G., Waldren, C.A., Geard, C.R., Yu, Z.Y., and Hei, T.K.(1999) Targeted cytoplasmic irradiation by alpha particles induces gene mutations. Proc. National Academy Science U.S.A. 96: 4959-4964. PMCID: PMC21799
  • Hei, T.K., Wu. L.J., Liu, S.X., Vannais, D., Waldren, C.A., and Randers-Pehrson, G.(1997) Mutagenic effects of a single and an exact number of alpha particles in mammalian cells. Proc. National Academy Sciences U.S.A. 94: 3765-3770. PMCID: PMC20515
  • Hong, M., Xu, A., Zhou, H., Wu, L., Randers-Pehron, G., Santella, R., Yu, Z., and Hei, T.K. (2010) Mechanism of genotoxicity induced by targeted cytoplasmic irradiation. Brit. J. Cancer 103: 1263-1268. PMCID: PMC2967061
  • Zhang, B., Davidson, MM., Zhou, H.N., Walker, WF., Hei, T.K. (2013) Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent mitochondrial fission. Cancer Research 73: 6700-6710. PMCID: PMC3934017.
  • Wu, J, Zhang B, Wuu, YR, Davidson MM, Hei TK. (2017) Targeted cytoplasmic irradiation and autophagy. Mutation Res 806: 88-97. PMCID: PMC5581273
Extracellular effects of ionizing radiation

Following up on the targeted cytoplasmic studies and using the single particle microbeam, my laboratory further shows unequivocally that cells that are NOT directly hit by a charged particle but in the vicinity of one that is or having received signals from such cells can also participate in the damage process. Radiation- induced non-targeted/ bystander effects, as it is called, represent a paradigm shift in our understanding of the target theory of ionizing radiation. My laboratory plays a major role in elucidating the mechanisms involved and the role of the out of field response in animal models.

  • Zhou, H.N., Randers-Pehrson, G., Waldren, C.A., Vannais, D., Hall, E.J. and Hei, T.K. (2000) Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc. National Academy Science U.S.A. 97: 2099-2104. PMCID: PMC15760
  • Zhou, H.Z., Suzuki, K., Randers-Pehrson, G., Vannais, D., Trosko, J., Waldren, C.A., and Hei, T.K. (2001) Radiation risk at low doses may be greater than we thought. Proc. National Academy Sci. U.S.A. 98:14410-14415. PMCID: PMC64695
  • Zhou, H.N., Ivanov, V., Gillespie, J., Geard, C.R., Amundson, S.A., Lieberman, H.B., and Hei, T.K. (2005) Mechanism of radiation induced bystander effect: role of COX-2 signaling pathway. Proc. National Academy Science U.S.A. 102: 14641-14646. PMCID: PMC 1253564
  • Chai, Y., Calaf, G.M., Zhou, H. Ghandhi, S.A., Elliston, C.D., Wen, G., Nohmi, T., Amundson, S. and Hei, T.K. (2013) Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. British J. Cancer 108: 91-98. PMCID: PMC3553512
  • Pei, H., Hu, W, Guo, Z, Chen H, Ma J, Mao W, Li B, Wang A, Wan J, Zhang J, Nie J, Zhou G, Hei TK. (2018) Long noncoding RNA CRYBG3 blocks cytokinesis by directly binding G-actin. Cancer Res. 78:4563-4572. PMCID: PMC6095725
Genotoxicity of arsenic

Arsenic is an important environmental contaminant affecting more than 100 million people worldwide through contaminated drinking water. Using a mutagenic assay system that can detect chromosomal mutations, my laboratory has shown that arsenic is genotoxic and the process involves generation of reactive oxygen and reactive nitrogen species. More recently, we have shown that arsenic induces apoptosis and altered differentiation in neural stem cells and may contribute to the reduced IQ and loss of cognitive function observed in children exposed to chronic environmental arsenic.

  • Hei, T.K., Liu, S.X., and Waldren, C.A. (1998) Mutagenicity of arsenic in mammalian cells: Role of reactive oxygen species. Proc. National Academy Science U.S.A. 95:8103-8107. PMCID: PMC20936.
  • Liu, S.X., Athar, M., Lippai, I., Waldren, C.A., and Hei, T.K. (2001) Induction of oxyradicals by arsenic: implications for mechanisms of genotoxicity. Proc. National Academy Science U.S.A. 98:1643-1648. PMCID: PMC29310.
  • Liu SX, Davidson MM, Tang XW, Walker WF, Athar M, Ivanov V and Hei TK. (2005) Mitochondrial damage mediates genotoxicity of arsenic in mammalian cells. Cancer Research 65: 3236-3242. PMID: 15833855.
  • Gong, X, Ivanov, VN and Hei TK. (2016) Tetramethylpyrazine down regulated arsenic induced heme oxygenase I and ARS2 expression by inhibiting Nrf2, NFkB,AP-1 and MAPK pathways in human proximal tubular cells. Arch. Toxicology 90(9):2187-200. PMCID: PMC4808507
Mechanism of asbestos carcinogenicity

Asbestos is a well-established human carcinogen and induces lung cancer and mesothelioma. The carcinogenic mechanism of asbestos is not clear. For over 30 years, my laboratory has been studying the how and why of fiber carcinogenesis. We have shown that asbestos, contrary to earlier belief that it is a non- genotoxic carcinogen, is indeed mutagenic when assay using model system that can detect large chromosomal deletions. The finding provide an epidemiological link to asbestos associated human mesothelioma that frequently show large scale chromosomal mutations. We further demonstrate that role of reactive radical species and the role of mitochondrial damage in the genotoxic process.

  • Hei, T.K., Piao, C.Q., He, Z.Y., Vannais, D., and Waldren, C.A. (1992) Chrysotile fiber is a potent mutagen in mammalian cells. Cancer Research 52: 6305-6309. PMID: 1330290
  • Xu, A., Wu, L.J., Santella, R., and Hei, T.K. (1999) Role of oxyradicals in mutagenicity and DNA damage induced by asbestos in mammalian cells. Cancer Research 59: 5615-5624. PMID: 10606236
  • Huang, S.X., Partridge, M.A., Ghandhi, S.A., Davidson, M. M., Amundson, S.A., and Hei, T.K. (2012) Mitochondrial derived reactive intermediate species mediated asbestos induced genotoxicity and oxidative stress-responsive signaling pathways. Environ. Hlth. Perspect. 120:840-847. PMCID: PMC3385428
  • Wang, M.M, Wang, Y.C, Wang, X.N, Liu, Y, Zhang, H, Chen, S.P, Hei, T.K, Wu, L.J, Xu, A (2015) Mutagenicity of ZnO nanoparticles in mammalian cells: Role of physicochemical transformations under the aging process. Nanotoxicology 9:972-982. PMID: 25676621

Selected Publications

Guo Z, Dai Y, Hu W, Zhang Y, Cao Z, Pei W, Liu N, Nie J, Wu A, Mao W, Chang L, Li B, Pei H,*Hei TK, *Zhou G. (2021) The long noncoding RNA CRYBG3 induces aneuploidy by interfering with spindle assembly checkpoint via direct binding with Bub3. Oncogene. Feb 9. doi: 10.1038/s41388-020-01601-8. PMID:33564066

Ivanov VN, Grabham PW, Wu CC, Hei TK (2020) Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures. Sci Rep. 10 (1):2687. doi: 10.1038/s41598-020-59468-4.32060308

Ye LF, Chaudhary KR, Zandkarimi F, Harken AD, Kinslow CJ, Upadhyayula PS, Dovas A, Higgins DM, Tan H, Zhang Y, Buonanno M, Wang TJC, Hei TK, Bruce JN, Canoll PD, Cheng SK, Stockwell BR (2020) Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers. ACS Chem Biol. 15(2):469-484. 31899616

Zhou G, Hu W, Pei H, Chen H, Hei TK. (2020) Recent progress on the Chinese space program and radiation research. Ann ICRP. 2020 Jul 31:146645320940828. doi: 10.1177/ 0146645320940828. PMID: 32734778

Cho K, Imaoka T, Klokov D, Paunesku T, Salomaa S, Birschwilks M, Bouffler S, Brooks AL,Hei TK, Iwasaki T, Ono T, Sakai K, Wojcik A, Woloschak GE, Yamada Y, Hamada N. (2019) Funding for radiation research: past, present and future. Int J Radiat Biol. Jan 2:1-25. doi: 10.1080/09553002.2018. PMID:30601684

Guo Z, Pei H, Nie J, Hu W, Zhang J, Ding J, Pan S, Li B,Hei TK, Chen W, Zhou G (2019) Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate. Chem Biol Drug Des. 2019 Jan 13. doi: 10.1111/cbdd.13477. PMID: 30637976

Ivanov VN, Wu J, Wang TJC,Hei TK (2019) Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells. Oncotarget 10(8):825-846. PMCID: PMC6368233

Hu W, Zhu L, Pei W, Pan S, Guo Z, Wu A, Pei H, Nie J, Li B, Furusawa Y, Konishi T,Hei TK, Zhou G (2019) Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma CellsIn VitroandIn Vivo. Oxid Med Cell Longev. Jun 2;2019:5254798.PMCID: PMC6589259

Gong X, Duan Y, Zheng J, Ye Z,Hei TK (2019) Tetramethylpyrazine Prevents Contrast-Induced Nephropathy via Modulating Tubular Cell Mitophagy and Suppressing Mitochondrial Fragmentation, CCL2/CCR2-Mediated Inflammation, and Intestinal Injury. Oxid Med Cell Longev. May 16;2019:7096912. PMCID:PMC6541991

Wang M, Wang J, Liu Y, Wang J, Nie Y, Si B, Liu Y, Wang X, Chen S,Hei TK, Wu L, Zhao G, Xu A (2019) Subcellular targets of zinc oxide nanoparticles during the aging process: role of cross-talk between mitochondrial dysfunction and endoplasmic reticulum stress in the genotoxic response. Toxicol Sci. Jun 7. doi: 10.1093/toxsci/kfz132. PMID31173148.

Chaudhary KR, Yan SX, Heilbroner SP, Sonett JR, Stoopler MB, Shu C, Halmos B, Wang TJC,Hei TK, Cheng SK (2019) Effects of β-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. J Clin Med. 2019 Apr 26;8(5). pii: E575. doi: 10.3390/jcm8050575. PMCID:PMC6572477

Hu W, Zhu L, Pei W, Pan S, Guo Z, Wu A, Pei H, Nie J, Li B, Furusawa Y, Konishi T,Hei TK, Zhou G. (2019) Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma CellsIn VitroandIn Vivo. Oxid Med Cell Longev. 2019 Jun 2;2019:5254798. PMCID: PMC6589259