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Michael Fessler to Establish Host Defense Group at NIEHS

By Eddy Ball
September 2006

Michael Fessler, M.D.
Michael Fessler, M.D. (Photo courtesy of Steve McCaw)

While most people think all of their organs are pretty special, to Dr. Michael Fessler, the lung is the pivotal organ in the human body's interaction with the environment. In his new position at NIEHS, the physician-researcher with board certification in internal, pulmonary and critical care medicine will serve as Clinical Investigator and head of the new Host Defense Group in the Laboratory of Respiratory Biology.

Combining his education and background as a clinician with his passion for research, Fessler will use a disease-oriented translational approach to develop possible clinical applications out of his group's work on the mechanism of infection, inflammation and induction of the lung's preprogrammed immune system response to the environment.

As Fessler describes his translational approach, "The overall strategy will be to use cell and animal models of human lung diseases (e.g., acute lung injury, emphysema) to discover new aspects of disease induction and to test out novel disease interventions." He is hopeful "that marrying 'discovery science' approaches, such as proteomics, to more traditional techniques will provide innovative bench-to-bedside insights, and accelerate their validation."

While the group will perform animal-based and cell-based studies, its efforts will also include clinical research using human samples, such as lung tissue and fluid from the lung. "Exposed as it is, the lung is a centrally important organ for environmental research," Fessler explains. "In its physiologic role of providing continuous gas exchange for the body, the lung is also a first line of defense against infection in which the inflammatory process has to be precisely controlled."

Fessler is convinced that lung-focused research can provide insight into acute respiratory distress syndrome, asthma, and interstitial lung disease, and also into inflammatory responses throughout the body. Combining his research work with the Host Defense Group, anticipated involvement with the work of the new NIEHS Clinical Research Unit and an adjunct clinical appointment at Duke, Fessler intends to keep his team ever-sensitive to the end purpose of its research -to improve patient outcomes.

Medical scientists often use the words "cascade" and "downstream" to describe the mechanisms of metabolic processes, especially harmful ones. The waterfall or flood metaphor is useful because it suggests the domino effect of a succession of biochemical stimulants and responses in the body. In a flood, the ultimate damage, the destruction of buildings for example, may actually result from something the water moved -earth, a rock or a tree -rather than directly from the water itself. Similarly, an environmental exposure will trigger a succession of responses that harm the body "downstream" from the initial environmental exposure. By tracing the pathway, the triggers and responses leading to the end result of inflammation, medical science may be able to short-circuit or ameliorate harm to the body.

Much of Fessler's recent research has focused in this way on the infection/inflammation cascade in lung tissue and how to impact it. Among his body of original scientific manuscripts and numerous presentations, two studies stand out as especially representative of his current research interests and translational approach. The first (2004) explored the mechanism of lipid raft regulation of inflammation induced by lipopolysaccharide (LPS) or endotoxin, a major component of gram-negative bacteria. Study results suggested the possibility that manipulation of cellular cholesterol content may offer an effective approach to modification of the innate immune response. Growing out of this study, the second (2005) examined the specific impact of lovastatin, a drug prescribed widely to reduce cholesterol levels and cardiovascular risk, in modulating pulmonary inflammation and the lung's host defense response. By confirming lovastatin's effects on immune function in the lung, the research team pointed towards possible clinical applications for statins in conditions such as acute respiratory distress syndrome.

Fessler comes to NIEHS with an impressive background in medical science, a sizable body of research, and experience with pulmonary and critical care medicine in clinical settings. After finishing his undergraduate work at Princeton University, the New Jersey native completed his medical training at Harvard and residency at Massachusetts General. From Boston, he moved west in 1999 for a Fellowship in Pulmonary Sciences and Critical Care Medicine at the University of Colorado Health Sciences Center. Teaching appointments followed at the University's School of Medicine, and in 2002, Fessler accepted an appointment at the National Jewish Medical and Research Center. He served as an Instructor and, later, Assistant Professor of Medicine at the Center prior to joining the Respiratory Biology Branch in August.

Fessler and his family have settled into their new home in Cary, where he and his wife spend much of their free time with their three-and-a-half-year-old son. When he can get away from his research, Fessler enjoys cycling. "Unfortunately, tenure-track academic positions are not very conducive to avid cycling," he laments.

His new home is located in a neighborhood with many younger children and convenient to NIEHS and cycling routes. Living in Cary also puts the Fesslers over two thousand miles closer to family back east in the Washington, DC/Baltimore area.

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