Major Areas of Research:
The Pulmonary, Critical Care and Sleep Medicine Division has an active research programs spanning clinical, translational and basic investigation. The entire division participates in its research mission, and its internationally known faculty of physician-investigators are leaders in their field. The success of the division’s research efforts can be seen in its outstanding mentoring of fellows to faculty positions, supporting junior faculty to independent research careers, and the international reputation of its senior investigators. The impact of the division’s research programs can be seen in its outstanding publication record and grant support. The division continues to grow its research portfolio with numerous grants continuing into next year and many submissions for future grants.
Control of Breathing - The control of breathing research group has been a major focus of the division for over 20 years. Currently 6 faculty members have active research programs in this area with independent, but overlapping areas of interest and strong collaboration as seen through their joint publication record. Dr. Kingman Strohl’s research is in sleep disordered breathing. He is currently investigating the genetic basis of differences in rat ventilatory patterns. He has just completed a comprehensive QTL analysis looking at two informative rat strains with varying respiratory patterns. With this information, he is now embarking on a high density mapping project of informative areas identified in the rat genome. Dr. Pingfu Feng’s expertise is in the development of sleep patterns with age, and small animal neural recording. His work seeks to explain the behavioral and biochemical basis of sleep/wake cycle ontogeny. His laboratory is unique in its ability to study continuous, long term, neural recordings in small animals in their natural state and environment. Dr. Ted Dick’s research is in pontine control of ventilation. His recent work involves the recording of multiple neurons from entire neural regions of the pons instead of single cells to identify their connections and cross-talk, and develop computer models of these interactions to understand the pontine diaphragmatic pacemaker. There is significant collaboration and complementation between Drs. Dick and Strohl with recent studies on the effect of CPAP on pontine regulation of breathing and cardiac function. Dr. Frank Jacono was a fellow in the Division’s Pulmonary and Critical Care Fellowship program. During the research component of his fellowship and while a junior faculty member, he worked on carotid body oxygen sensing with Nanduri Prabhakar, PhD, Vice Chair of Physiology and Biophysics and an international expert in carotid body oxygen sensing. His current projects revolve around understanding respiratory variability, its mechanism, and its prognostic meaning.
Immunology/Inflammation – Currently Richard Silver, MD, is actively working in pulmonary immunology and inflammation. Dr. Silver’s research program is based around the study of human immunity to M. tuberculosis. He has developed an antigen stimulation system using direct bronchoscopic instillation of PPD into the lung, followed by bronchoalveolar lavage cell recovery from the “immunized” area, as well as the contra-lateral “non-immunized” lung. The development of this novel approach is yielding important information about how protective immune responses are mobilized to the lung in response to inhaled pathogens. In addition, organ-specific responses are being studied as the preliminary evaluation of the efficacy of tuberculosis vaccines. As an extension of Dr. Silver’s interest in innate immunity he is also studying the granulomatous inflammation that develops during tuberculosis infections and sarcoidosis. Studying the response of individuals with sarcoidosis to inflammatory agents, and similar responses in mouse models, he is exploring the hypothesis that the host’s abnormal immune response to a number of different pathogens results in granulomatous inflammation.
Elliott Dasenbrook, MD, MHS, is an epidemiologist and clinical researcher whose research is focused on exploring inflammatory/infectious mechanisms that are important contributors to CF morbidity and mortality and designing novel intervention strategies that will improve outcomes for those affected by this disease. Currently, Dr. Dasenbrook is studying the role of methicillin-resistant staphylococcus aureus (MRSA) infections in individuals with cystic fibrosis. Dr. Dasenbrook has designed a clinical trial to test if a high intensity treatment protocol can eradicate persistent MRSA from the respiratory tract of children and adults with CF. In addition, using molecular techniques, he is exploring MRSA virulence factors that may be associated with persistent infections.
Rena Mehra, MD, MS, completed a Sleep, Neurobiology and Epidemiology research fellowship after her Pulmonary and Critical Care Fellowship, mentored by Drs. Redline and Strohl. During the fellowship she completed a Masters of Science in Clinical Investigation. Her current hypothesis explores specific pathways of oxidative stress as mediators linking sleep-disordered breathing and cardiovascular disease. The understanding of the inter-relationship of oxidative stress and sleep-disordered-breathing, and its impact on cardiac disease may allow identification of individuals at risk for any sleep-related co-morbidity, help target drug therapy in high-risk individuals, and identify intermediate outcomes to use in subsequent observational and interventional studies. Dr. Mehra is the recipient of an RO1 and R21.
Clinical Research: Clinical research within the division is focused on pulmonary artery hypertension (PAH), acute lung injury and hypoxemia. Our PAH program is under the direction of Robert Schilz, DO, PhD. Dr. Schilz has a national reputation in PAH and is involved in the design and implementation of many new PAH drug trials. Our intensive care unit is part of the NIH sponsored ARDS Network and we actively participate in all ARDS Network clinical trial development, design, implementation and patient accrual. Clinical research in hypoxemia is progressing as part of the NIH funded Long-term Oxygen Therapy Trial. Our division is part of a city wide consortium participating in the trial with Kingman Strohl, MD, participating in the trial.