Chronic Disease Etiology and Prevention
Chronic diseases, especially cancer, cardiovascular disease, and respiratory diseases, are the leading causes of morbidity and mortality worldwide—are among the most common, costly, and preventable of all health problems. For lung cancer and respiratory disease, tobacco smoking and exposure to toxic chemicals are important risk factors. Recently, ambient air pollution has been implicated in increasing the incidence and mortality from lung cancer and from cardio-pulmonary diseases.
Research in this area is focused on discovering novel molecular mechanisms that drive the pathophysiology of major chronic diseases to develop prevention and therapeutic strategies to improve public health. The research done by graduate students, postdoctoral fellows, and faculty has led directly to an enhanced understanding of the molecular, cellular, biochemical, pathobiological, and physiological changes that represent early stages and progression of many chronic diseases.
Research Highlight
E-cigarette Exposure Impairs Immune Responses in Mouse Model
COPD is a major public health problem for both the developed and the developing worlds. Characterized by chronic bronchitis and emphysema, COPD is the third leading cause of death in the U.S. COPD affects 24 million Americans and 210 million worldwide. Bacterial and viral acute respiratory infections cause exacerbations leading to a severe decline in lung function in patients with COPD. Current treatments are largely symptomatic and supportive, but do not reverse the underlying biological defect in the lung.
Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated.
Our researchers have found that e-cigarettes compromise the immune system in the lungs and generate some of the same potentially dangerous chemicals found in traditional nicotine cigarettes.
Presently, research determines that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, an inhalation chamber for E-cig exposure was developed. Since COPD patients are susceptible to bacterial and viral infections, the effects of E-cigs were also tested on immune response.
Associated Faculty
Shyam Biswal, PhD
Biswal's research focuses on therapeutic resistance of cancer due to a gain-of-function mutation in transcription factor Nrf2. Using patient-derived xenografts in humanized immunocompetent mice and GEM models, his lab aims to understand the mechanisms of oncogenic cooperation and metabolic adaptation in cancer cells. He's also investigating the systemic and pulmonary effects of air pollution as well as the health effects of recent tobacco products, such as electronic cigarettes and water pipes.
Joseph Bressler, PhD*
Bressler's laboratory studies how environmental pollutants affect neurodevelopment with specific interests in autism and fetal alcohol syndrome.
Jessie Buckley, PhD*
Dr. Buckley's research is grounded in the developmental origins of health and disease framework and focuses on determining effects of early life exposure to endocrine disrupting chemicals. She is actively engaged in evaluating the environmental obesogen hypothesis, which posits that chemical exposures during critical developmental windows can result in permanent changes that predispose individuals toward obesity.
John Groopman, PhD*
Groopman has devoted his research efforts to developing biomarkers for use in human studies of environmental toxicant exposures and applying these biomarkers to public health interventions. His research involves the development and application of molecular biomarkers of exposure, dose, and effect from environmental carcinogens. The environmental carcinogens studied include agents that are naturally occurring in the diet as well as those produced as a result of mobile and stationary sources of air pollution.
Mark Kohr, PhD*
Kohr's research seeks to define the underlying redox-sensitive signaling pathways and the mechanistic consequences of redox-based post-translational protein modifications in healthy and diseased myocardium. S-nitrosylation, which results from the addition of a nitric oxide moiety to a cysteine thiol−one example of a redox-based modification that has been implicated as a critical regulator of many processes that govern normal cellular physiology, including protein function and stability, protein-protein interaction, and protein localization.
Brian Schwartz, MD*
A large part of Schwartz's research applies the methods of occupational, environmental, and molecular epidemiology to studying the health effects of chemicals. Health effects of interest include those in the central nervous (e.g., cognitive function, brain structure), peripheral nervous, cardiovascular, and renal systems.
Fenna Sillé, PhD*
The focus of Dr. Sillé's research is understanding the effects of environmental exposures on the development and function of our immune system. Her major research directions are:
1. Understanding the long-term effects of early-life arsenic exposures on immunity and (infectious) disease risk. - Currently studying the interaction between arsenic and tuberculosis,
2. Establishing an integrated platform for immunotoxicity testing of early-life chemical exposures,
3. Investigating the effects early-life exposures on immunological memory and vaccine efficacy.
Zhibin Wang, PhD*
Wang's long-term research goal is to determine how epigenetic codes, including patterns of DNA methylation and combinatorial patterns of simultaneously occuring histone modifications, are established and how this establishment goes awry upon environmental stimuli, thereby contributing to human diseases (such as cancers and autoimmune diseases).
Marsha Wills-Karp, PhD
Wills-Karp's research activities focus on defining the environmental and genetic determinants of allergic airway diseases such as asthma. She has recently turned her attention to how the gut microbiome alters susceptibility to allergen and PM-induced asthma.
*Denotes faculty who are accepting PhD students.