Xing Laboratory

Research Overview

Chengguo (CX) Xing, Ph.D., is a professor and the Frank A. Duckworth Eminent Scholar Chair in the department of medicinal chemistry at the University of Florida College of Pharmacy. Xing received his B.S. degree from the Dalian University of Technology and obtained his Ph.D. degree from Arizona State University. He completed postdoctoral training at Harvard University. Xing started his independent research career as an assistant professor at the University of Minnesota in 2003, and he was promoted to associate professor in 2009 and professor in 2014. He joined the faculty at the University of Florida in August 2016.

Affiliations

• UF Cancer Center
• Society of Toxicology
• American Association for Cancer Research
• American Association of the Colleges of Pharmacy
• American Chemical Society

Research Summary

My research program attempts to understand tobacco carcinogenesis, build cancer risk stratification, and develop preventive interventions with the ultimate research goal of facilitating cancer prevention as a key pillar to support effective cancer management. Lung cancer has been our current disease model, because one of every 16 people in the US will develop lung cancer in their lifetime and over 140,000 US citizens lose their lives annually while tobacco exposure is the major risk factor for lung cancer and smokers are the high-risk populations. To achieve our ultimate research goal, we train, integrate and collaborate with research teams with expertise in organic chemistry, chemical biology, molecular biology, cellular biology, pharmacology, bioanalytical chemistry, and clinical science. There are three major and complementary directions.

Direction 1: Understanding tobacco carcinogen-induced lung carcinogenesis and developing physiologically more relevant carcinogenesis animal models

As the major risk factor for lung cancer, tobacco exposure leads to tobacco carcinogen-induced DNA damage, which has long been proposed as the root cause. Our work however suggest that DNA damage is necessary but not sufficient for carcinogenesis. Potentially there are other molecular and cellular signaling processes perturbed by tobacco exposure that contribute to lung carcinogenesis. We also hypothesize that psychosocial stress, whether tobacco exposure related or not, is another carcinogen or co-carcinogen in promoting lung carcinogenesis. These concepts have not been quantitatively analyzed. We have been developing bioanalytical methods and built new carcinogenesis animal models, which are expected to integrate these physiologically relevant factors to better mimic lung carcinogenesis in smokers and to quantitatively test our hypothesis.

Direction 2: Developing non-invasive cancer risk surrogates and building a multivariable cancer risk predictive model

Although tobacco use accounts for 85 – 90% lung cancer incidence, only 10 – 15% smokers will eventually develop lung cancer. One key challenge is whether it is possible to predict which smoker has a higher risk of lung cancer WAY BEFORE current diagnosis, which would significantly improve the feasibility of cancer prevention and transform lung cancer preventive management. Our long-term goal is to develop a non-invasive peripheral risk surrogate matrix to fill in this critical gap. We are currently developing carcinogen-specific urinary DNA adductomics, plasma protein adductomics, and carcinogenesis-selective metabolomics as practical and non-invasive peripheral surrogates in predicting lung cancer risk. With respect to the experimental models, we are integrating the lung tumorigenesis animal models and various human clinical samples to explore the feasibility of this paradigm-shift strategy.

Direction 3: Kava in lung cancer chemoprevention

Upon identifying individuals of higher risk of lung cancer, effective and feasible interventions would be needed to prevent lung cancer development. We have been evaluating various natural and unnatural entities to search for effective lung cancer chemopreventive agent. Kava has been rigorously investigated in our group over the past 15 years – we are known more as “The kava group” than our real name. Stimulated by promising epidemiological observations, we hypothesized that kava has the potential to reduce cancer risk via multiple mechanisms. Using several well-characterized lab animal models, we have demonstrated the chemopreventive potential of kava against lung, prostate, and colon tumorigenesis. Particularly for tobacco carcinogen-induced lung tumorigenesis, kava and its active ingredient demonstrate outstanding in vivo efficacy with a solid safety profile. The mechanistic investigation also led to the discovery of several non-invasive biomarkers that greatly improve the feasibility of its clinical evaluation with one pilot trial accomplished. Stimulated by the exciting results from the pilot clinical trials, we are working to implement more rigorous clinical trials.

In summary, our research program aligns at the interface of organic chemistry and biology, focusing on lung cancer early diagnosis and prevention, integrating medicinal chemistry, pharmacognosy, pharmacology, molecular/cellular biology, and clinical science. We have established successful collaborations with researchers from diverse backgrounds. Our research has been highly translational with commercial potentials, demonstrated by two start-up companies based on our research results. One clinical trial completed and two clinical trials are expected to be initiated in 2020. Hopefully more will come in the future with our team effort. Without neglecting other responsibilities, maintaining a strong, vibrant and well-funded research program that provides exceptional training for graduate students and post-docs is our top priority.

Representative publications

1. Wang, Y.; Narayanapillai, S. C.; Strayer, L.; Upadhyaya, P.; Kingston, R.; Lu, J.; Salloum, R.; Hecht, S.; Hatsukami, D.; Fujioka, N.; Xing, C. The Impact of One-week Dietary Supplement Kava on Biomarkers of Tobacco Exposure and Nitrosamine-based Carcinogenesis among Active Smokers. Cancer Prevention Research. 2020, revision under review.
2. Wang, Y.; Narayanapillai, S. C.; Hu, Q.; Fujioka, N.; Xing, C. Biomonitoring of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB) from Albumin Adducts as a Surrogate Biomarker for Assessment of Human Exposure to Tobacco-Specific Nitrosamines. Toxic. Lett. 2019, 311: 11-16.
3. Wang, Y.; Narayanapillai, S. C.; Hu, Q.; Fujioka, N; Xing, C. Contribution of Tobacco Use and 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to Three Methyl DNA Adducts in Urines. Res. Toxicol.2018, 31(9): 836-838.
4. Bian, T.; Vijendra, K. C.; Wang, Y.; Meacham, A.; Hati, S.; Cogle, C. R.; Sun, H.; Xing, C. Exploring the structure activity relationship and mechanism of a chromene scaffold (CXL series) for its selective anti-proliferative activity towards multidrug resistant cancer cells. J. Med. Chem. 2018, 61(15):6892-6903.
5. Puppala, M.; Narayanapillai, S. C.; Leitzman, P.L.; Upadhyaya, P.; OˈSullivan, M. G.; Hecht, S. S.; Lu, L.; Xing, C.* Pilot in vivo structure-activity relationship of dihydromethysticin (DHM) in blocking tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced DNA damage and lung tumorigenesis in A/J mice. J. Med. Chem. 2017, 60(18):7935-7940.
6. Narayanapillai, S.C.; Lin, S-H.; Leitzman, P.; Upadhyaya, P.; Baglole, C. J.; Xing, C. Dihydromethysticin (DHM) blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced O⁶-methylguanine independent of aryl hydrocarbon receptor (AhR) in C57BL/6 female mice. Res. Toxicol., 2016, 29(11): 1828-1834.
7. Narayanapillai, S.C.; von Weymarn, L.B.; Carmella, S.G.; Leitzman, L.; Upadhyaya, P.; Hecht, S.S.; Murphy, S.E.; Xing, C.* Dietary Dihydromethysticin (DHM) Increases Glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-Butanol (NNAL) in A/J Mice, Potentially Enhancing its Detoxification. Drug Metab. Dispos. 2016, 44(3):422-427.
8. Narayanapillai1, S.; Leitzman, P.; O’Sullivan, M. G.; Xing, C.* Flavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Res. Toxic. 2014, 27(10), 1871-1876.
9. Narayanapillai1, S.; Balbo, S.; Leitzman, P.; Grill, A.; Upadhyaya, P.; Shaik, A.; Zhou, B.; O’Sullivan, M. G.; Lu, J.; Peterson, L.; Hecht, S. S.*; Xing, C.* Dihydromethysticin (DHM) from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice. Carcinogenesis 2014, 35(10), 2365-2372.
10. Leitzman, P.; Naayanapillai, S. C.; Balbo, S.; Zhou, B.; Shaik, A.; O’Sullivan, M. G.; Upadhyaya, P.; Hecht, S. S.; Lu, J.; Xing, C.* Kava Completely Blocks 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced Lung Tumorigenesis via Reducing DNA Damage in A/J Mice. Cancer Prevention Res. 2014, 1(7): 86-96.