Stephen Hecht, PhD

Wallin Land Grant Professor of Cancer Prevention, Department of Laboratory Medicine and Pathology

Stephen Hecht

Contact Info

hecht002@umn.edu

Office Phone 612-624-7604

Fax 612-624-3869

Office Address:
CCRB 2-148

Mailing Address:
Masonic Cancer Research Ctr.
1st Floor Mailroom CCRB
2812A
2231 6th St. SE
Minneapolis, MN 55455

Wallin Land Grant Professor of Cancer Prevention, Department of Laboratory Medicine and Pathology

Graduate Faculty, Department of Medicinal Chemistry

Professor, Masonic Cancer Center (MCC)

Professor, Department of Pharmacology


PhD, Massachusetts Institute of Technology (Organic Chemistry), 1968

BS, Duke University (Chemistry) 1964

Summary

The goal of research in the Hecht laboratory is to understand mechanisms of metabolic activation and DNA modification by carcinogens in tobacco products and the human environment, and apply this knowledge to cancer prevention. The laboratory focuses on the properties of carcinogenic nitrosamines, polycyclic aromatic hydrocarbons, and aldehydes. Using state of the art mass spectrometry and related techniques, analytical methods are developed for quantitation of carcinogen and toxicant metabolites and DNA adducts in laboratory animals treated with carcinogens and in human urine, blood and tissues. These biomarkers are applied in collaborative clinical and epidemiologic studies to investigate human carcinogen exposure, metabolism, and susceptibility to cancer. Stable isotope labeled carcinogens and their analogues are employed in studies with users of tobacco products to track individual differences in metabolism. The effects of naturally occurring potentially cancer chemopreventive compounds on carcinogen metabolism in humans are also investigated.

Awards & Recognition

  • Elected American Association for the Advancement of Science Fellow, 2014
  • Joseph Cullen Award, American Society of Preventive Oncology, 2012
  • Selected as Editor-in-Chief, Chemical Research in Toxicology, 2012
  • Elected American Chemical Society Fellow, 2009
  • Founders Award, Division of Chemical Toxicology, American Chemical Society, 2009
  • Academy for Excellence in Health Research, Academic Health Center, University of Minnesota, 2006
  • AACR Cancer Research and Prevention Foundation Award for Excellence in Cancer Prevention Research, 2006
  • Merit Award, National Cancer Institute, 2004
  • Flight Attendant Medical Research Institute Dr. William Cahan Distinguished Professor Award, 2002
  • Alton Ochsner Award Relating Smoking and Health, 2001
  • American Cancer Society Research Professor, 2000-2009
  • Outstanding Investigator Grant, National Cancer Institute, 1987-2001

Research

Research Summary/Interests

Dr. Hecht’s laboratory is focused on understanding the ways tobacco smoke constituents cause cancer. To do this he and his colleagues study the mechanisms by which these compounds enter the human body, are metabolized, and ultimately bind to DNA, causing mutations that result in cancer. Cigarette smoke contains more than 70 carcinogens. Hecht focuses on several including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and certain volatiles such as formaldehyde, acetaldehyde, and acrolein that are formed during the combustion process.

Hecht’s research team has developed methods to analyze human urine for these compounds and their metabolites. These methods, which employ mass spectrometry as a key analytic technology, enable his laboratory to take part in studies of thousands of smokers. Hecht’s group also uses mass spectrometry methods to analyze the DNA damage caused by the carcinogens at the level of stereochemistry, which shows the relative spatial arrangement of atoms and molecules.

The goal of Hecht’s research is two-fold: First, to provide evidence in support of ongoing regulation of tobacco products due to their harm to human health, and second, to find ways to identify the susceptible smoker. That smoking causes lung cancer is well established, but it is not yet possible to identify which smokers are most likely to contract lung cancer, which would allow for early intervention. Collaboration between research groups in the fields of genetics, biochemistry, psychology and other fields will be needed to turn promising leads of an individual smoker’s susceptibility to lung cancer into a preventive strategy.

Hecht has a long-standing collaboration with a University colleague in psychiatry who is studying the mechanisms of addiction. Given that more than a billion people of the world’s population of seven billion people are smokers, including an estimated 45 million in the U.S. and 300 million in China, the impact of learning the biological and psychological mechanisms involved in tobacco smoke addiction is a major public health challenge and opportunity. Understanding these mechanisms also can lead to the identification of smoking prevention strategies and potential chemopreventive agents.

Publications

  • Hatsukami, D., Stepanov, I., Severson, H., Jensen, J.A., Lindgren, B.R., Horn, K., Khariwala, S.S., Martin, J., Carmella, S.G., Murphy, S.E., and Hecht, S.S. Evidence supporting product standards for carcinogens in smokeless tobacco products, Cancer Prev. Res.8: 20-26, 2015.
  • Hecht, S.S., Koh, W-P., Wang, R., Chen, M., Carmella, S.G., Murphy, S.E., and Yuan, J-M. Elevated levels of mercapturic acids of acrolein and crotonaldehyde in the urine of Chinese women in Singapore who regularly cook at home. PLOS ONE doi:10.1371/journal.pone.0120023, 2015.
  • Hecht, S.S., Carmella, S.G., Kotandeniya, D., Pillsbury, M.E., Chen, M., Ransom, B.W.S., Vogel, R.I., Thompson, E., Murphy, S.E., and Hatsukami, D.K. Evaluation of toxicant and carcinogen metabolites in the urine of e-cigarette users versus cigarette smokers. Nicotine Tob. Res., 17: 704-709, 2015. doi:10.1093/ntr/ntu218.
  • Park, S.L., Carmella, S.G., Ming, X., Stram, D.O., Le Marchand, L., and Hecht, S.S. Variation in levels of the lung carcinogen NNAL and its glucuronides in the urine of cigarette smokers from five ethnic groups with differing risks for lung cancer. Cancer Epidemiol. Biomarkers & Prev. 24: 561-569, 2015.
  • Hatsukami, D.K., Severson, H., Anderson, A., Isaksson, R.V., Jensen, J., Broadbent, B., Murphy, S.E., Carmella, S.G., and Hecht, S.S. Randomized clinical trial of snus vs. medicinal nicotine among smokers interested in product switching. Tobacco Control doi:10.1136/tobaccocontrol-2014-052080 2015.
  • Kotandeniya, D., Carmella, S.G., Ming, X., Murphy, S.E., and Hecht, S.S. Combined analysis of the tobacco metabolites total cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in human urine. Anal. Chem. 87: 1514-1517, 2015.
  • Zarth, A.T., Murphy, S.E., and Hecht, S.S. Benzene oxide is a substrate for glutathione-S-transferases. Chem-Biol. Interact. 242: 390-395, 2015.
  • Park, S.L., Carmella, S.G., Chen, M., Patel, Y., Stram, D.O., Haiman, C.A., LeMarchand, L., and Hecht, S.S. Mercpaturic acids derived from the toxicants acrolein and crotonaldehyde in the urine of cigarettes smokers from five ethnic groups with differing risks for lung cancer. PLOS ONE doi:10.1371/journal.pone.0124841, 2015.
  • Khariwala, S.S., Carmella, S.G., Tepanov, I., Bandyopadhyay, D., Nelson, H.H., Yueh, B., Hatsukami, D.K., and Hecht, S.S. Self-reported tobacco use does not correlate with carcinogen exposure in smokers with head and neck cancer. The Laryngoscope 125: 1844-1848, 2015.
  • Kotandeniya, D., Carmella, S.G., Pillsbury, M.E., and Hecht, S.S. Combined analysis of N?-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in the urine of cigarette smokers and e-cigarette users. J. Chromatog. B. 1007: 121-126, 2015.
  • Ma, B., Villalta, P., Zarth, A., Kotandeniya, D., Upadhyaya, P., Stepanov, I., and Hecht, S.S. Comprehensive high resolution mass spectrometric analysis of DNA phosphate adducts formed by the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Chem. Res. Toxicol. 28: 2151-2159, 2015.
  • Hecht, SS and E. Szabo. Fifty Years of Tobacco Carcinogenesis Research: From Mechanisms to Early Detection and Prevention of Lung Cancer. Cancer Prev Res 2014;7:1-8
  • Hecht, SS. It Is Time to Regulate Carcinogenic Tobacco-Specific Nitrosamines in Cigarette Tobacco. Cancer Prev Res 2014;7:639-647.
  • Balbo, S., James-Yi, S., Johnson, C.S., O’Sullivan, M.G., Stepanov, I., Wang, M., Bandyopadhyay, D., Kassie, F., Carmella, S., Upadhyaya, P., Hecht, S.S. (S)-N'-Netrosonornicotine, a Constituent of Smokeless Tobacco, is a Powerful Oral Cavity Carcinogen in Rats. Carcinogenesis 2013; 34(9) 2178-2183