Michael Fessler, M.D.

Senior Investigator

Immunity, Inflammation, and Disease Laboratory / Clinical Investigation of Host Defense


Acting Clinical Director


David P Rall Building
111 Tw Alexander Dr
Research Triangle Park, NC 27709



Research Topics

The Host Defense Group investigates molecular and cellular mechanisms of the innate immune response to environmental 'pathogen-associated molecular patterns' (PAMPs), using the macrophage and the murine lung as in vitro and in vivo model systems. Within this platform, our focus is in defining novel areas of crosstalk between the innate immune response and cholesterol trafficking. Our central hypothesis is that cholesterol/membrane trafficking and innate immunity signaling are intrinsically coupled processes, and that perturbations in each therefore regulate the other. Our group in particular has a special interest in defining emerging roles for cholesterol trafficking in regulation of inflammatory and host defense events in the lung. Given the high prevalences of dyslipidemia and inflammatory lung disease in modern society and the translational nature of our program, these studies have potential for impacting both public health and the clinical care of individual patients.

Our laboratory's major directive is that the manipulation/perturbation of cell cholesterol will yield novel: 1) mechanisms underlying the induction and regulation of the innate immune response; 2) determinants of inflammatory phenotype in human subjects; and 3) sites for intervening in innate immunity and the diseases in which it plays a role.


Dr. Fessler is Chief of the Immunity, Inflammation, and Disease Laboratory. Fessler received his A.B. in philosophy from Princeton University in 1992, and his M.D. from Harvard Medical School in 1996. He subsequently completed an internal medicine residency at Massachusetts General Hospital, and a pulmonary-critical care medicine fellowship at University of Colorado Health Sciences Center. During his research fellowship, Dr. Fessler trained in the innate immunity laboratory of Dr. G. Scott Worthen at National Jewish Health, and then joined the National Jewish faculty from 2002-2006. In 2006, Dr. Fessler started as a Tenure Track Investigator in the IRP of the NIEHS, in which role he heads the Clinical Investigation in Host Defense Group. Dr. Fessler has received several awards, including the NIEHS Early Career Award, NIEHS Intramural Research Award, and the American Thoracic Society Carol Basbaum Award, and serves on the editorial board of PLoS One and as a Faculty Member of F1000.

Selected Publications

  1. Rai P, Janardhan KS, Meacham J, Madenspacher JH, Lin WC, Karmaus PWF, Martinez J, Li QZ, Yan M, Zeng J, Grinstaff MW, Shirihai OS, Taylor GA, Fessler MB. IRGM1 links mitochondrial quality control to autoimmunity. Nat Immunol. 2021;22(3):312-321.
  2. Lin WC, Gowdy KM, Madenspacher JH, Zemans RL, Yamamoto K, Lyons-Cohen M, Nakano H, Janardhan K, Williams CJ, Cook DN, Mizgerd JP, Fessler MB. Epithelial membrane protein 2 governs transepithelial migration of neutrophils into the airspace. J Clin Invest. 2020;130(1):157-170.
  3. Madenspacher JH, Azzam KM, Gowdy KM, Malcolm KC, Nick JA, Dixon D, Aloor JJ, Draper DW, Guardiola JJ, Shatz M, Menendez D, Lowe J, Lu J, Bushel P, Li L, Merrick BA, Resnick MA, Fessler MB. p53 Integrates host defense and cell fate during bacterial pneumonia. J Exp Med. 2013;210(5):891-904.
  4. Smoak KA, Aloor JJ, Madenspacher J, Merrick BA, Collins JB, Zhu X, Cavigiolio G, Oda MN, Parks JS, Fessler MB. Myeloid differentiation primary response protein 88 couples reverse cholesterol transport to inflammation. Cell Metab. 2010;11(6):493-502.
  5. Madenspacher JH, Morrell ED, Gowdy KM, McDonald JG, Thompson BM, Muse G, Martinez J, Thomas S, Mikacenic C, Nick JA, Abraham E, Garantziotis S, Stapleton RD, Meacham JM, Thomassen MJ, Janssen WJ, Cook DN, Wurfel MM, Fessler MB. Cholesterol 25-hydroxylase promotes efferocytosis and resolution of lung inflammation. JCI Insight. 2020;5(11).

Related Scientific Focus Areas

This page was last updated on Monday, July 1, 2024