Environmental, occupational, and cancer research


Alison Bauer inspecting sample

Research interests

Role of environmental and occupational exposures in respiratory disease, including chronic inflammation and carcinogenesis

  • Constituents of secondhand smoke (e.g., polycyclic aromatic hydrocarbons, PAHs)
  • Contaminants of particulate air pollution and soil (e.g., PAHs, vanadium pentoxide)
  • Mechanistic role(s) of bioactive lipids in toxicant-induced adverse lung effects

Role of the innate immune system in pulmonary neoplastic and non-neoplastic diseases

  • Toll-like receptors and additional innate immune markers in pulmonary neoplasia
  • Epiregulin involvement in the pathogenesis of NSCLC
  • TLR4 and heat shock protein 70 (Hsp70) in ozone induced lung injury and inflammation
Prevention of respiratory diseases through intervention and new therapeutics

Current projects, lab members, collaborators, and recent publications

Investigating the role of PAHs in respiratory diseases induced by secondhand smoke and other environmental exposures, such as air pollution

Secondhand smoke (SHS) and air pollution are associated with many diseases including respiratory diseases, such as childhood and adult asthma, chronic obstructive pulmonary disease (COPD), and lung cancer.[1,2] Some occupations in the U.S. still have high exposures to SHS, such as casino workers, and environmentally with apartment dwellers.[3-7]  In 2018, the World Health Organization (WHO) estimated 9 in 10 people globally breathe polluted, toxic air. The WHO was quoted stating that “Air pollution is the new tobacco”. Unfortunately, due to the latency of many chronic pulmonary diseases, individuals exposed to SHS and air pollution can observe effects years after exposure. Thus, the effects of these exposures are a real concern for human health at all ages.

Our research in collaboration with Dr. Brad Upham (Michigan State University) focuses on the most abundant PAHs in SHS and air pollution, the  two-four-ringed PAHs (such as fluoranthene)[8-10] and their role in pulmonary inflammation and cell-cell communication (see SHS PAHs and adverse lung effects; SHS PAHs and eicosanoid signaling; SHS PAHs and inflammatory mediators). Recent studies focus on investigation of downstream signaling events following several “omics” studies. We are particularly interested in understanding the role of bioactive lipids in mediating the effects of PAHs in diseases such as asthma and cancer. 

 

Current projects

 

References

 

  1. CDC (2008) Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses—United States, 2000-2004. Atlanta, GA. 1226–1228 p.
  2. CDC (2010) Vital Signs: Nonsmokers' Exposure to Secondhand Smoke —United States, 1999-2008. Atlanta, GA. 1141-1146 p.
  3. Achutan C et al., (2011) J Occup Environ Med 53: 346-351.
  4. Arjomandi M, Haight T, Redberg R, Gold WM (2009) J Occup Environ Med 51: 639-646.
  5. Beatty AL, Haight TJ, Redberg RF (2011) Environ Health 10: 81.
  6. Ebbert JO et al. (2007) Environ Health 6: 28.
  7. Pilkington PA, Gray S, Gilmore AB (2007) BMC Public Health 7: 257.
  8. Lee HL, Hsieh DP, Li LA (2010) Chemosphere 10.1016/j.chemosphere.2010.09.045.
  9. Moir D et al. (2008) Chem Res Toxicol 21: 494-502.
  10. Severson RF et al. (1976) Isolation, identification, and quantification of polynuclear aromatic hydrocarbons in tobacco smoke. In: Freudenthal RI, and Jones, P.W., editor. Carcinogenesis- A comprehensive survey Vol 1 Polynuclear aromatic hydrocarbons: Chemistry, metabolism, and carcinogenesis. New York, New York: Raven Press. pp. 253-270.

 

Role of the innate immune system in lung cancer

Current projects

  • Investigation of epiregulin involvement in the pathogenesis of NSCLC (see Epiregulin is required for lung tumor promotin in a murine carcinogenesis model) in collaboration with Drs. Backos and Nield (UCD).
  • Investigation of MUC5AC in lung carcinogenesis in collaboration with Dr. Evans (UCD SOM).
  • Understanding the predictive capacity and therapeutic utility of toll-like receptors in lung cancer based on these previous studies in our laboratory
    • In our paper on Toll-like receptor expression in human lung cancer, we provided evidence that in humans, the mRNA expression of TLRs1-10 associate with improved survival outcomes in NSCLC, specifically early-stage adenocarcinoma
    • Identification of differential innate immune cell signatures involved in mediating the responses in mice lacking TLR4 in a mouse lung cancer model (see Alexander et al. 2016)
    • Evidence that TLR4-deficient mice were significantly more sensitive to lung tumor promotion and pulmonary inflammation at both early and advanced stages of disease than the wild-type mice (see Bauer et al 2005, 2009)

Current lab members

Former lab members

  • Ross Osgood, PhD, Former graduate student in Toxicology; Currently a postdoctoral fellow at Harvard School of Public Health 
  • Carla Alexander, PhD, Former post-doctoral fellow; Currently at Nexgen Pathology, Trinidad 
  • Elizabeth Rondini, PhD, Former post-doctoral fellow; Research Scientist, Wayne State 
  • Katelyn Siegrist, Ph.D., Former post-doctoral fellow, Mylan Pharmaceuticals
  • PRA, Deedee Romo, Denver Health Clinical lab technician
  • Undergraduate students from University of Colorado Denver and Boulder
    • Ka-Na Xiong
    • Julie Xiong
    • Rana Brooks
    • Victoria Churchill-Hinton
    • Zachary Leins
    • Dylan Van
  • Undergraduates from School of Mines
    • Lindsey Nield

National 

  • Dr. Brad Upham, Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 
  • Dr. Donald Backos, Department of Pharmaceutical Sciences and Director of the Computational Chemistry and Biology Core, University of Colorado Denver, Aurora, CO 
  • Dr.Nichole Reisdorph, Department of Pharmaceutical Sciences and Director of Mass Spectrometry Core, University of Colorado Denver, Aurora, CO 
  • Dr. Seyed Javad Moghaddam, Department of Pulmonary Medicine, M.D. Anderson Cancer Center, Houston, TX 
  • Dr. Linda Sargent, Molecular Genetics Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia (retired) 
  • Drs.Steven Kleeberger and Hye Youn Cho, Laboratory of Respiratory Biology, Environmental Genetics Group, National Institute of Environmental Health Sciences, RTP, NC 
  • Dr. Christopher Evans, Department of Medicine-Pulmonary Sciences & Critical Care, UC Anschutz, Aurora, CO

 

International 

  • Dr. Heiko Käfferlein, Head for the Center for Toxicology, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute der Ruhr-Universität-Bochum (IPA) 
  • Dr. Sabine Plöttner, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute der Ruhr-Universität-Bochum (IPA) 
  • Dr. Pavel Babica, Masaryk University, Research Center for Toxic Compounds in the Environment, Brno, Czech Republic 
  • Dr. Iva Sovadinova​, Masaryk University, Research Center for Toxic Compounds in the Environment, Brno, Czech Republic  ​

Romo D, Velmurugan K, Upham BL, Dwyer-Nield LD, Bauer AK. Dysregulation of Gap Junction Function and Cytokine Production in Response to Non-Genotoxic Polycyclic Aromatic Hydrocarbons in an In Vitro Lung Cell Model. Cancers (Basel). 2019 Apr 23;11(4). doi: 10.3390/cancers11040572. PubMed PMID: 31018556; PubMed Central PMCID: PMC6521202. 

Siegrist KJ, Romo D, Upham BL, Armstrong M, Quinn K, Vanderlinden L, Osgood RS, Velmurugan K, Elie M, Manke J, Reinhold D, Reisdorph N, Saba L, Bauer AK. Early Mechanistic Events Induced by Low Molecular Weight Polycyclic Aromatic Hydrocarbons in Mouse Lung Epithelial Cells: A Role for Eicosanoid Signaling. Toxicol Sci. 2019 May 1;169(1):180-193. doi: 10.1093/toxsci/kfz030. PubMed PMID: 30690640; PubMed Central PMCID: PMC6484882. 

Shin N, Velmurugan K, Su C, Bauer AK, Tsai CSJ. Assessment of fine particles released during paper printing and shredding processes. Environ Sci Process Impacts. 2019 May 3;. doi: 10.1039/c9em00015a. [Epub ahead of print] PubMed PMID: 31049512. 

Bauer AK, Umer M, Richardson VL, Cumpian AM, Harder AQ, Khosravi N, Azzegagh Z, Hara NM, Ehre C, Mohebnasab M, Caetano MS, Merrick DT, van Bokhoven A, Wistuba II, Kadara H, Dickey BF, Velmurugan K, Mann PR, Lu X, Barón AE, Evans CM, Moghaddam SJ. Requirement for MUC5AC in KRAS-dependent lung carcinogenesis. JCI Insight. 2018 Aug 9;3(15). doi: 10.1172/jci.insight.120941. eCollection 2018 Aug 9. PubMed PMID: 30089720; PubMed Central PMCID: PMC6129115. 

Johnson M, Alsaleh N, Mendoza RP, Persaud I, Bauer AK, Saba L, Brown JM. Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms. PLoS One. 2018;13(3):e0193499. doi: 10.1371/journal.pone.0193499. eCollection 2018. PubMed PMID: 29566008; PubMed Central PMCID: PMC5863960. 

Bauer AK, Velmurugan K, Plöttner S, Siegrist KJ, Romo D, Welge P, Brüning T, Xiong KN, Käfferlein HU. Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co-carcinogenic properties in an in vitro murine lung epithelial cell model. Arch Toxicol. 2018 Mar;92(3):1311-1322. doi: 10.1007/s00204-017-2124-5. Epub 2017 Nov 23. PubMed PMID: 29170806; PubMed Central PMCID: PMC5866845. 

Bauer AK, Upham BL, Rondini EA, Tennis MA, Velmuragan K, Wiese D. Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease. Oncotarget. 2017 Nov 3;8(54):91860-91875. doi: 10.18632/oncotarget.19463. eCollection 2017 Nov 3. PubMed PMID: 29190881; PubMed Central PMCID: PMC5696147. 

Osgood RS, Upham BL, Bushel PR, Velmurugan K, Xiong KN, Bauer AK. Secondhand Smoke-Prevalent Polycyclic Aromatic Hydrocarbon Binary Mixture-Induced Specific Mitogenic and Pro-inflammatory Cell Signaling Events in Lung Epithelial Cells. Toxicol Sci. 2017 May 1;157(1):156-171. doi: 10.1093/toxsci/kfx027. PubMed PMID: 28329830; PubMed Central PMCID: PMC5808746. 

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