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When you come to a fork in the road, take it.
(Yogi Berra)

I have always been intrigued by the way chemicals, the good and the bad kind, alter biology. While in high school I started exploring different fields that would allow me to pursue this idea of studying the way chemicals alter biology, bringing me to the fields of Pharmacology and Toxicology. In my native Germany at the time the way to pursue a career in either of these fields was to get a basic degree in Pharmacy or Medicine first, followed by an advanced degree in either Toxicology or Pharmacology. Since I was not really interested in Medicine, I started studying Pharmacy at the University of Bonn, in Germany.

Fork #1: Through a number of different circumstances, an opportunity to go to Seton Hall University in New Jersey on a tennis scholarship presented itself to me. So, after one semester at the University of Bonn, I packed my bags (and tennis rackets), moved to South Orange, NJ, and started as a Biology Major at Seton Hall. In the beginning, I made this move more as a “gap year” to become immersed in the English language, which I thought would be beneficial in my long-term career. However, I really enjoyed college and stayed. I ended up graduating in 3 years, looking to continue my education getting a PhD in either Pharmacology or Toxicology.

Fork #2: The application process for graduate programs was interesting, daunting, and exciting. For personal reasons, I limited my search for PhD programs in Pharmacology/Toxicology to the NY/NJ/PA region. Even though Rutgers has an amazing program (and they offered me to potentially play tennis with my remaining year of eligibility), I decided to join the program at New York University. I was particularly drawn to their inhalation facility, their down-to-earth faculty, and research focus with direct relevance to policy and regulation. Overall, like every graduate student, I had my ups and downs, but genuinely enjoyed my dissertation research and mentors. They provided me with the right amount of advice, guidance, and independence. Dr. Lung Chi Chen is a leader in inhalation toxicology and was my primary mentor. He understood how to help me reach my potential and encouraged me to develop collaborations to enrich my research. He and I collaborated with Dr. Elizer (Eli) Flescher, an immunologist and signal transduction expert, resulting in what in today’s terms would be called an “inter-disciplinary” collaboration to uncover air pollutant induced signal transduction pathways resulting in modified immune responses. Both Lung Chi and Eli knew that mentoring is not a “one size fits all” approach, and tailored their mentorship to my personality, skills, and needs. In other words, they were always there when I needed them, but they also provided me with the independence and freedom that fit my personality. They also understood that I am inherently motivated and competitive and that there was no need for them to encourage me to work harder. We were quite productive, published several papers on the signaling cascade activated by ozone in epithelial cells, ultimately generating new questions we did not know how to address (more on that later).

Fork #3: Towards the end of my PhD, I started thinking about my long-term career path. At that point, I really did not want to pursue a career in academia, which is one of the reasons why I turned down a postdoc at a prestigious lab at NHLBI/NIH. I wanted to continue basic research, but in an environment that would open up opportunities towards research positions in government or industry. At a meeting of the Society of Toxicology (SOT), I started exploring postdoctoral research opportunities in different settings. By pure chance, I was introduced to investigators from the U.S. EPA and was presented with an opportunity to conduct a postdoctoral research project in collaboration with the U.S. EPA, but through the University of North Carolina, and more specifically, the Center for Environmental Medicine and Lung Biology. This opportunity seemed perfect: it had one foot in academia and one foot in government research. My postdoctoral research offered me so many new and exciting research opportunities, that I felt like a kid in a candy store. As a postdoc, you have the skills and intellect to conduct independent research, but no pressure of reaching specific milestones, like defending your dissertation or the pressure of a tenure clock. During my postdoc at UNC, I was able to greatly advance my understanding of pollutant-induced signal transduction, focusing more on particulate air pollutants, like metals and diesel exhaust. Working with my colleagues at the EPA, like Drs. James Samet and Robert Devlin, I also gained a glimpse at how research data can inform policy and the process involved in modifying regulations. The ability to continue hypothesis-driven research that could also inform air pollution regulation was very intriguing to me.

Fork #4: My postdoc period solidified my desire to continue a career in academia, but also illustrated the need to demonstrate that I could obtain independent funding and develop my own research program. During my postdoc, I was introduced to investigators at UNC interested in respiratory viral infections. Linking air pollutant exposures with respiratory viral infections was a new research niche, combining my interest in respiratory toxicology and immunology. This was the basis for my own independently funded project for research on diesel exhaust and influenza infections through the Long-Range Research Initiative of the American Chemistry Council. Data obtained through this project provided the basis for my first NIESH R01 examining how diesel exhaust alters the susceptibility to and severity of influenza virus infections. Having independent funding also allowed me to recruit the first graduate student into my lab. Mentoring students and watching how they mature into independent researchers is still the best part of my job!

Fork #5: I was able to expand my interest in combining exposure to toxicants and their effects on respiratory viral infections to cigarette smoke, including secondhand smoke exposures, which is still one of the main inhalational threats to children. New collaborations with Dr. Terry Noah, a pediatric pulmonologist, allowed me to expand my research approaches to include human clinical studies. Developing safe and non-invasive mechanisms to study influenza virus infections presented a novel research tool to study how inhaled toxicants modify respiratory viral infections in humans in vivo. This research resulted in several NIH-funded grants, numerous publications, and the observations that pollutants, such as cigarette smoke, diesel exhaust, and woodsmoke significantly affect viral replication and antiviral host defense responses in humans.

Fork #6: Presenting my research to different groups allowed me to meet new investigators all over the country. One of those visits, to Vanderbilt University, resulted in a new research truly cross-disciplinary research collaboration to address research gaps from my dissertation research. Dr. Ned Porter at Vanderbilt University is a lipid chemist with specific interests in oxidized cholesterol species (oxysterols) and their ability to form lipid-protein adducts. Because of my prior research in ozone, he and I started a collaboration examining whether a) ozone could generate these oxysterols, b) they could form lipid-protein adducts, and c) this results in modified biological function. As mentioned above, work from my dissertation left unanswered how ozone would initiate the signaling cascades in epithelial cells. Because ozone is highly reactive, it was always assumed that it forms some type of ozone reaction product, which in turn would cause the biological effects. Now, over 15 years later, I was presented with an opportunity to address this knowledge gap and examine how ozone-derived oxysterols modify cellular proteins, resulting in altered cellular function. This ongoing research project has expanded to other lipid oxidation products and continues to be an exciting collaboration between the lipid chemistry group at Vanderbilt and inhalation toxicologists at UNC.

Fork #7: In 2009, the Obama administration signed into law the Family Smoking Prevention and Tobacco Control Act. This provided the FDA with the jurisdiction to regulate tobacco products. At that point E-cigarettes and Vaping were pretty new and not covered under the new law. The increasing popularity of e-cigarettes in the U.S. showed the need for additional oversight and regulation of these new and emerging tobacco products. However, there was very little research on the potential health effects of e-cigarettes. As part of the FDA-funded UNC Tobacco Center of Regulatory Sciences (TCORS), we were charged with identifying potential health effects and toxicities caused by these products or their components. Research we conducted in my lab on e-cigarette toxicities, specific flavorings, and potential biomarkers of human health effects were needed to inform regulations on these products. While this research uncovered important new pathways through which e-cigarette compounds, such as flavoring chemicals or aerosolized humectants can affect epithelial cells and respiratory immune cells, our research also contributed to research-based recommendations to the FDA.

Fork #8: The research on e-cigarettes also hit me personally. Both my kids are teenagers and provided first-hand accounts of how much e-cigarettes affected our high schoolers. At the same time, my colleagues in Pediatrics, who take care of teenagers, did not even recognize the more advanced models of e-cigarettes and had no idea how to ask questions about vaping behavior so it could be recorded in their medical records. Our research was informing policy, but our research needed to reach relevant stakeholders, like health care providers and teenagers, a lot faster to have an impact. Through the Community Engagement Core (CEC), I was introduced to Dr. Kathleen Gray and Ms. Dana Haine, who have helped me and my team translate our research directly to relevant stakeholders. Taking my research from the lab and translating it to teenagers was a challenging task. Presenting laboratory-based research and scientific observations to my scientific peers is what I had been trained to do since my graduate training. Communicating primary research to the community required a whole new set of skills but has a much more immediate impact, something I try to instill in all of my trainees.

Through all of this, I rose through the ranks, became a fully tenured Professor in the Departments of Pediatrics, Microbiology & Immunology and Environmental Sciences and Engineering, Director of the Center for Environmental Medicine, Asthma, and Lung Biology, Director for the Curriculum in Toxicology and Environmental Medicine Training program, and I still love what I do! My absolute favorite part of this job is the PhD hooding ceremony at UNC (probably the only way I will ever set foot on the basketball court of the UNC Dean Dome), representing the conclusion of another successful journey of a trainee getting his/her PhD in Toxicology and Environmental Medicine from UNC. I am looking forward to the next fork in my road and I am excited to take it!

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