About

Sharon Murphy, PhD, is a professor in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota. She is also the Director of Graduate Studies. Dr. Murphy received her Doctorate from the University of Colorado. Her research focuses on characterizing nicotine and carcinogen metabolism in different individuals, with the goal of understanding how these differences affect lung cancer risk. Her studies include investigating the metabolism of nicotine, nitrosamines, and other tobacco-related carcinogens, particularly the tobacco-specific nitrosamine NNK, which requires cytochrome P450-catalyzed metabolism to exert its carcinogenic potential. Her laboratory has characterized the roles of P450 2A6 and P450 2A13 enzymes in nicotine and cotinine metabolism, noting that P450 2A6 is present in human liver while P450 2A13 is found in the lung. Recent work has shown that both enzymes are inactivated during nicotine metabolism, and her team is exploring the mechanisms behind this inactivation. These enzymes also catalyze the metabolic activation of tobacco-specific carcinogens, with P450 2A13 exhibiting higher efficiency in NNK metabolism despite their structural similarity. Her research includes studying the structure-activity relationships of these enzymes through site-directed mutagenesis and examining the influence of enzyme polymorphisms on nicotine and nitrosamine metabolism. Her work aims to refine lung cancer screening algorithms and improve nicotine addiction and smoking cessation treatments by understanding individual metabolic differences.

Research topics

• Internal medicine
• Medicine
• Political Science
• Biochemistry
• Chemistry
• Physiology
• Environmental health
• Psychology
• Toxicology
• Pharmacology
• Pathology
• Biology
• Family medicine
• Clinical psychology

Selected publications

• The association of epigenetic age acceleration with internal smoking dose, risk of lung cancer, and all-cause mortality in cigarette smokers: the Multiethnic Cohort study

  Clinical Epigenetics · 2026-04-22

  articleOpen access

  Among cigarette smokers, higher internal smoking dose is associated with elevated lung cancer risk and mortality, independent of smoking pack-years. Some measures of epigenetic age acceleration (EAA) are associated with cigarette smoking status and exposure, as well as lung cancer risk and overall mortality. No study has examined the association between EAA measures and internal smoking dose (total nicotine equivalents (TNE; nmol/mL)), and their shared relationship with lung cancer incidence and mortality in a multiethnic population. From a subgroup of Multiethnic Cohort Study participants who smoked cigarettes at the time of biospecimen collection (n = 1969), six epigenetic clocks were computed using blood-based DNA methylation (DNAm) array data. EAA measures were computed by calculating the residuals that results from regressing an epigenetic clock on chronological age. The association of urinary TNE with EAA measures were assessed using linear regression models, adjusted for age, sex, body mass index (BMI; kg/m2), DNAm-based estimates of blood cell composition, population stratification, and self-reported pack-years of cigarette smoking. To evaluate the associations of EAA with incident lung cancer risk (n = 176 cases) and all-cause mortality (n = 780 deaths) (from 13 years of follow-up), Cox proportional hazard models, with age as the time metric, adjusted for decade of birth, sex, BMI, years of education, creatinine, DNAm-based estimates of blood cell composition, population stratification, self-reported pack-years, and urinary TNE, were used. A standard deviation (SD) increase of log-TNE was statistically significantly associated with increased AgeAccelPheno (beta = 0.416, 95% Confidence Interval (CI)=0.134-0.698)), AgeAccelGrim (beta = 0.771, 95%CI=0.603-0.939), and DunedinPACE (beta = 0.015, 95%CI=0.010-0.020). A SD increase of AgeAccelGrim (Hazard Ratio (HR) = 1.40; 95% CI 1.16–1.71) and DunedinPACE (HR = 1.31; 95% CI 1.11–1.55) were associated with a risk of lung cancer, whereas a SD increase of AgeAccelDNAm-based telomere length was inversely associated with lung cancer risk (HR = 0.79; 95% CI 0.67–0.93). These findings were similar for the hazard of all-cause mortality. Our study suggests that circulating methylation-based biomarkers of biological aging may provide information on lung cancer risk and all-cause mortality beyond that of self-reported pack-years and a (short-term) biomarker of internal smoking dose. If replicated, our findings suggest that epigenetic clocks may inform higher risk groups for prevention strategies.

  PublisherDOI

• Effects of unventilated versus ventilated filtered cigarettes on smoking behaviour and biomarkers of smoke exposure in a randomised clinical trial

  Tobacco Control · 2026-05-20

  articleOpen access

  BACKGROUND: Banning cigarette filter ventilation has been raised by some public health researchers and organisations because it has misled people who smoke to believe they are smoking a safer cigarette. AIM: To examine the potential effects of banning ventilated filters on smoking behaviour and biomarkers of toxicant exposures. TRIAL DESIGN: Randomised controlled trial with parallel semi-blind study design. METHODS: People who smoke (n=164) ventilated cigarettes daily were randomised to smoke 'ventilated' (≈27% ventilation) or 'unventilated' (≈0.11% ventilation) study cigarettes for 6 weeks. Non-inferiority testing was conducted on the changes in urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL) and cigarettes per day (CPD) between the two cigarette groups. Superiority testing was conducted for differences in smoking intensity (amount of nicotine in cigarette butts), other exposure biomarkers and subjective responses. RESULTS: The unventilated condition was generally non-inferior to the ventilated condition for change in total NNAL (3% greater for unventilated vs ventilated, less than the non-inferiority 15% margin but with wide variability with an upper bound of 95% CI of 16%, p=0.064) and in CPD (0.22 cigarettes greater for unventilated vs ventilated, lower than the non-inferiority margin of 2, p<0.001). There were no significant differences between the two groups in other biomarkers (p>0.05). Less intensity of smoking was observed with unventilated cigarettes (difference of changes=-0.04 mg nicotine, p=0.002), aligning with higher self-reported ratings of nicotine strength (p=0.005) and aversion (p=0.028). CONCLUSIONS: Overall, banning filter ventilation is unlikely to lead to greater toxicant exposures but certain subgroups might experience greater exposures.

  PublisherDOI

• Supplementary Table 5. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Association of urinary biomarkers of smoking-related toxicants with lung cancer incidence - Multiethnic Cohort Study (MEC), by low total nicotine equivalents (TNE) and high TNE.&lt;/p&gt;

  PublisherDOI

• Supplementary Table 4. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Association of various characteristics at time of urine collection with lung cancer incidence in the Multiethnic Cohort (MEC) subcohort of current smokers (n=140 cases).&lt;/p&gt;

  PublisherDOI

• Supplementary Table 6. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Histologic cell-type by race/ethnicity of the Multiethnic Cohort (MEC) smokers with lung cancer (N=140 cases only) identified during study follow-up.&lt;/p&gt;

  PublisherDOI

• CYP2A6 Activity and Deuterated 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) Metabolism in Cigarette Smokers

  Chemical Research in Toxicology · 2025-09-15 · 2 citations

  articleSenior authorCorresponding

  Smoking is the leading cause of lung cancer. Differences in CYP2A6-catalyzed nicotine metabolism affect smoking dose and intensity, which, in turn, can affect lung cancer risk. CYP2A6 also catalyzes the bioactivation of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To determine the contribution of CYP2A6 to the metabolic activation of NNK, a group of Japanese American and Native Hawaiian smokers with little or no CYP2A6 activity was recruited to smoke [pyridyl-D4]-NNK-containing cigarettes for a week. [Pyridyl-D4]-4-hydroxy-4-(3-pyridyl)butanoic acid (D4-hydroxy acid), the urinary product of NNK α-hydroxylation, the major bioactivation pathway, was quantified in these individuals and in an equal number of smokers with “normal” CYP2A6 activity. In expectation of low D4-hydroxy acid levels, a sensitive nanoflow LC-MS/MS assay was developed. CYP2A6 activity was measured as the plasma ratio of 3′-hydroxycotinine to cotinine, which is the nicotine metabolite ratio (NMR). The average concentration of D4-hydroxy acid in 24 h urine samples over 3 days was 20 ± 14 fmol/mL in low NMR (<0.05) smokers (n = 8) versus 33 ± 18 fmol/mL (p = 0.056) in “normal” NMR (>0.3) smokers (n = 8). The total D4-hydroxy acid excreted by the low NMR group was half that of the higher NMR group (29.1 ± 16.8 versus 59.7 ± 45.3 pmol/24h, p = 0.048). These data support the role of CYP2A6 in the metabolic activation of NNK. However, it is unlikely that more modest differences in CYP2A6 activity, for example, as might be seen across smokers of European ancestry, would significantly impact NNK bioactivation. The influence of CYP2A6 activity on nicotine metabolism and the associated carcinogen uptake is likely the primary influence of CYP2A6 activity on a smoker’s risk of lung cancer, not a modest effect on the metabolic activation of NNK, one of several lung carcinogens in tobacco smoke.

  PublisherDOI

• Supplementary Table 2. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Age-standardized incidence rates (ASIR) and 95% confidence intervals (CI) for lung cancer among a subcohort of Multiethnic Cohort (MEC) Study current smokers - overall and by race/ethnicity&lt;/p&gt;

  PublisherDOI

• Supplementary Figure 1. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Distribution plot of pack-years and urinary biomarkers of smoking-related toxicants both without and with transformation for the Multiethnic Cohort (MEC) subcohort of current smokers at time of urine collection. Figure A. Distribution plot of pack-years without transformation; Figure B. Distribution plot of pack-years divided by the overall population standard deviation (with transformation); Figure C. Distribution plot of total nicotine equivalents (TNE) without transformation; Figure D. Distribution plot of TNE with transformation; Figure E. Distribution plot of the ratio of total trans 3’-hydroxycotinine (3-HCOT)/cotinine (Total 3-HCOT/cotinine) without transformation; Figure F. Distribution plot of Total 3-HCOT/cotinine with transformation; Figure H. Distribution plot of 4-(methylnitrosamino)-1-3-pyridyl)-1-butanol (Total NNAL) without transformation; Figure I. Distribution plot of Total NNAL with transformation; Figure J. Distribution plot of S-phenylmercapturicacid (SPMA) without transformation; Figure J. Distribution plot of SPMA with transformation; Figure K. Distribution plot of 3-hydroxypropyl mercapturic acid (3-HPMA) without transformation; Figure L. Distribution plot of 3-HPMA with transformation; Figure M. Distribution plot of phenanthrene tetraol(PheT) without transformation; Figure N. Distribution plot of PheTwith transformation; Figure O. Distribution plot of 3-hydroxyphenanthrene (PheOH) without transformation; Figure P. Distribution plot of PheOH with transformation; Figure Q. Distribution plot of PheT/PheOH (a proposed biomarker of metabolic activiation of polycyclic aromatic hydrocarbons) without transformation; Figure R. Distribution plot of PheT/PheOH with transformation; Figure S. Distribution plot of cadmium (Cd) without transformation; Figure T. Distribution plot of Cd with transformation; Plot U. Distribution plot of (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α) without transformation; Figure V. Distribution plot of 8-iso-PGF2α with transformation.&lt;/p&gt;

  PublisherOA PDFDOI

• A watercress drink increases detoxification of common environmental carcinogens such as acrolein and benzene: results of a randomized clinical trial

  Carcinogenesis · 2025-12-26

  article

  Human exposure to toxicants and carcinogens occurs via polluted air, the diet, occupational settings, endogenous processes, and tobacco products. The glutathione-S-transferase detoxification pathway resulting in the excretion of mercapturic acids is one of the most important human systems for processing and excreting toxicants and carcinogens. Maximizing effectiveness of this pathway through dietary modifications can potentially decrease the impact of such exposures. We conducted a two-site clinical trial with a crossover, single blind (to participants) design, randomized to order of product receipt comparing levels of selected urinary mercapturic acids when participants consumed a drink made from freeze-dried watercress (3× daily, 2 weeks) naturally containing 2-phenethyl isothiocyanate (PEITC) vs. a placebo drink containing maltodextrin (3× daily, 2 weeks) with a 4-week washout between the treatment periods. Two hundred forty participants (157 F) were recruited and 188 (125 F, 152 non-smokers) were compliant and completed the study. Among compliant subjects, urinary mercapturic acid detoxification products of acrolein, acrylonitrile, benzene, crotonaldehyde, methacrolein, and methyl vinyl ketone increased significantly (P ≤ 0.002), with the largest increases being observed for the mercapturic acids of acrolein (65.6%) and benzene (37.3%), both P < 0.001. Consumption of a drink, three times daily, prepared from freeze-dried watercress containing PEITC (total of approximately 40 mg/day) significantly increased the detoxification of 6 of 7 environmental toxicants and carcinogens monitored. The results indicate that watercress consumption can ameliorate exposure to environmental toxicants and carcinogens. These results are particularly timely and relevant to exposures to atmospheric pyrolysis products resulting from wildfires. Clinical trial registration number: NCT03978117.

  PublisherDOI

• Supplementary Table 3. from Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study

  2025-11-26

  articleOpen access

  &lt;p&gt;Geometric mean and 95% confidence intervals for urinary biomarkers of smoking-related toxicants among the Multiethnic Cohort (MEC) subcohort of current smokers and incident lung cancer cases&lt;/p&gt;

  PublisherDOI

Recent grants

• NIH Grant R01CA084529

  NIH · $1.6M · 2013

• NIH Grant R01CA074913

  NIH · $566k · 2001

• NIH Grant RC2HL101405

  NIH · $1.2M · 2012

• Genetic and epigenetic risk markers for lung cancer in former smokers

  NIH · $58.0M · 2009–2027

• Evaluating New Nicotine Standards for Cigarettes

  NIH · $126.0M · 2011–2025

Frequent coauthors

• Stephen S. Hecht

  192 shared

• Loı̈c Le Marchand

  Cancer Center of Hawaii

  148 shared

• Steven G. Carmella

  107 shared

• Dorothy K. Hatsukami

  96 shared

• Sungshim L. Park

  Cancer Center of Hawaii

  90 shared

• Daniel O. Stram

  80 shared

• Lynne R. Wilkens

  72 shared

• Linda B. von Weymarn

  54 shared

Awards & honors

• Dr. James E. Rubin Medical Memorial Award
• Graduating Medical Student Research Award
• Veneziale-Steer Award
• Dr. Marvin and Hadassah Bacaner Research Awards
• Schmidt Steer Award