Cory Hogaboam, Ph.D.
Professor
Department of Pathology

hogaboam@umich.edu

Our research laboratory addresses two major themes related to chronic pulmonary disease. The first theme relates to cellular and molecular immune mechanisms that regulate the pulmonary growth and persistence of fungus in a number of experimental murine models. Specifically, we examine Aspergillus fumigatus , an ubiquitous fungal pathogen that initiates a broad spectrum of diseases ranging from lethal invasive growth to allergy and asthma. Our data to date has revealed that key immune cells such as myeloid cell progenitors, macrophages, and dendritic cells bridge the pulmonary innate and adaptive immune responses to this fungal pathogen. The second theme is more translational as we explore a grouping of clinical diseases referred to as idiopathic interstitial pneumonias (IIPs). IIPs are characterized by a lethal fibrotic response due to an exuberant fibroproliferative response by collagen producing cells in the lung. Using human tissues and isolated human cell populations, we are using large-scale genomic, proteomic and novel animal model approaches to explore the etiopathogenesis of these diseases, and, more importantly, identify novel therapeutic targets in IIPs.

Representative Publications

Buckland K.F., O'Connor E.C., Coleman E.M., Lira S.A., Lukacs N.W., Hogaboam C.M. Remission of chronic fungal asthma in the absence of CCR8. J. Allergy Clin. Immunol., 119(4):997-1004, 2007.

Meneghin, A., Hogaboam, C.M. Infectious disease, the innate immune response, and fibrosis. J. Clin. Invest., 117(3): 503-508, 2007.

Pierce E.M., Carpenter K.J., Jakubzick C., Kunkel S.L., Flaherty K.R., Martinez F.J., Hogaboam C.M.   Therapeutic targeting of CCL21 or CCR7 abrogates pulmonary fibrosis induced by the adoptive transfer of human pulmonary fibroblasts into immunodeficient mice.  Am. J. Pathol., 170:1152-1164, 2007.

Moore B.B., Hogaboam C.M. Murine models of pulmonary fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. Feb; 294(2):L152-60, 2008.

Trujillo G., O'Connor E., Kunkel S.L., Hogaboam C.M. CCR4 deficiency protects mice from bleomycin-induced pulmonary fibrosis via the novel regulation of alternative activation of macrophages . Am. J. Pathol., 172(5):1209-21, 2008.

Meneghin A., Choi E.S., Evanoff H.L., Kunkel S.L., Martinez F.J., Flaherty K.R., Toews G.B., Hogaboam C.M.  TLR9 is expressed in idiopathic interstitial pneumonia and its activation promotes in vitro myofibroblast differentiation.  Histochem. Cell Biol., Jul 17 Epub ahead of print, 2008.

Buckland K.F., O'Connor E., Murray L.A., Hogaboam C.M. Toll like receptor-2 modulates both innate and adaptive immune responses during chronic fungal asthma in mice. Inflamm. Res., in press, 2008.

Meneghin A., Choi E.S., Evanoff H.L., Kunkel S.L., Martinez F.J., Flaherty K.R., Toews G.B., Hogaboam C.M. TLR9 is expressed in idiopathic interstitial pneumonia and its activation promotes in vitro myofibroblast differentiation. Histochem. Cell Biol., 130(5): 979-992, 2008.

Buckland K.F., O’Connor E., Murray L.A., Hogaboam C.M. Toll like receptor-2 modulates both innate and adaptive immune responses during chronic fungal asthma in mice. Inflamm. Res., 57(8): 379-387, 2008.

Murray L.A., Knight D., McAlonan L., Argentieri R., Joshi A., Shaheen F., Jordan J., San Mateo L.R., Cunningham M., Alexopolou L., Flavell R.A., Sarisky R. T., Hogaboam C.M. Deleterious role of TLR3 during hyperoxia-induced acute lung injury. Am. J. Respir. Crit. Care Med., 178: 1227-1237, 2008.

Ramaprakash H., Ito T., Standiford T.J., Kunkel S.L., Hogaboam C.M. TLR9 modulates immune responses to Aspergillus fumigatus conidia in immunodeficient and allergic mice. Infect. Immun., 77(1): 108-119, 2008.

Joshi A.D., Schaller M., Lukacs N.W., Kunkel S.L., Hogaboam C.M. Toll like receptor 3 modulates immunopathology during Th2-driven immune responses in the lung. Eur. J. Immunol., 38(12): 3436-3449, 2008.

Joshi A.D., Fong D.J., Oak S.R., Trujillo G., Flaherty K.R., Martinez F.J., Hogaboam C.M. IL-17 mediated immunopathogenesis in experimental hypersensitivity pneumonitis. Am. J. Respir. Crit. Care Med., 179: 705-716, 2009.

Hartigan A.J., Westwick J., Jarai G., Hogaboam C.M. CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergilliosis. J. Immunol., in press, 2009.

Ramaprakash H., Hogaboam C.M. Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and independent manner. Int. Archives Allergy Immunol., in press, 2009.

Hartigan A.J., Westwick J., Jarai G., Hogaboam C.M. CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergilliosis. J. Immunol., 183: 5171-5179, 2009.

Ramaprakash H., Hogaboam C.M. Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and independent manner. Int. Arch. Allergy Immunol., 152(2):98-112, 2009.

Smith M., Gangireddy S., Narala V., Hogaboam C.M., Standiford T.J., Christensen P.J., Kondapi A.K, Reddy R.C. Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury. Am. J. Physiol. - Lung Cell. Mol. Physiol., Epub ahead of print Jan. 8, 2010.

Zavitz C.C.J., Bauer C.M.T., Gaschler G.J., Fraser K.M., Strieter R.M., Hogaboam C.M., Stampfli M.R. MIP-2 dependent inflammatory immunopathology drives illness in bacterial superinfection of influenza virus. J. Immunol., Epub ahead of print Jan. 11, 2010.

Fong D.J., Hogaboam C.M., Matsuno Y., Akira S., Uematsu S., Joshi A.D. TLR6 drives IL-17A expression during experimental hypersensitivity pneumonitis. Immunology, Epub ahead of print Jan. 11th, 2010.

Rosada R.S., Moreira A.P., Frantz F.G., Puri R.K., Rahman A., Standiford T.J., Zarate-Blades C.R., Silva C.L., Hogaboam C.M. Therapeutic efficacy of Cintredekin Besudotox (IL13-PE38QQR) in murine lung fibrosis is unaffected by immunity to Pseudomonas aeruginosa Exotoxin A. PLoS One, Jan 15; 5(1):e8721, 2010.

Cavassani K.A., Wen H., Moreira A.P., Schaller M.A., Carson IV W., Ishii M., Lindell D.M., Lukacs N.W., Keshamouni V.G., Hogaboam C.M., Kunkel S.L. The post sepsis-induced expansion and enhanced function of regulatory T cells creates an environment to potentiate tumor growth. Blood, Epub ahead of print Feb. 3, 2010.

Murray L.A., Rosada R., Moreira A.P., Joshi A., Kramer M.S., Hesson D.P., Argentieri R.L., Mathai S., Gulati M., Herzog E.L., Hogaboam C.M. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One, 5(3): e9683, March 2010.

Moreira A.P., Fong D., Rosada R., Murray L.A., Hesson D., Hogaboam C.M. Differential role of short pentraxins in the activation of macrophages during fungal spore-induced asthma. J. Allergy Clin. Immunol., in press, 2010.

Hartigan A.J., Kallal L.E., Hogaboam C.M. CCR7 impairs hematopoiesis following hematopoietic stem cell transplantation increasing susceptibility to invasive aspergillosis. Blood, in press, 2010.

Trujillo G., Meneghin A., Flaherty K.R., Scholl L.M., Myers J.L., Kazerooni E.A., Gross B.H., Oak S.R., Coelho A.L., Evanoff H.L., Day E., Toews G.B., Joshi A.D., Schaller M.A., Waters B., Jarai G., Westwick J., Kunkel S.L., Martinez F.J., Hogaboam C.M.  TLR9 differentiates rapidly from slowly progressive forms of idiopathic pulmonary fibrosis. Science Transl. Med., 2(57): p. 57ra82, 2010. PMCID: PMC3235647.

Buckland K.F., Ramaprakash H., Murray L.A., Carpenter K.J., Choi E.S., Kunkel S.L., Lukacs N.W., Xing Z., Aoki N., Hartl D., Hogaboam C.M.  Triggering receptor expressed on myeloid cells-1 (TREM-1) modulates immune responses to Aspergillus fumigatus during fungal asthma in mice.  Immunol. Invest. May 19, 2011. PMID: 21592044.

Ramaprakash H., Shibata T., Duffy K.E., Ismailoglu U.B., Bredernitz R., Moreira A.P., Coelho A.L., Das A.M., Fursov N., Chupp G.L., Hogaboam C.M.  Targeting ST2L potentiates CpG-mediated therapeutic effects in a chronic fungal asthma model.  Am. J. Pathol., 179(1): 104-115.  May 14, Epub ahead of print, 2011. PMCID: PMC3123853.

Oak S.R., Murray L.M., Herath A., Sleeman M., Anderson I., Joshi A.D., Coelho A.L., Flaherty K.R., Toews G.B., Knight D.A., Martinez F.J., Hogaboam C.M.  A microRNA processing defect in rapidly progressing idiopathic pulmonary fibrosis.  PLOS One, 6(6): e21253. June 21, Epub ahead of print, 2011. PMCID: PMC3119674.

Moreira A.P., Cavassani K.A., Ismailoglu U.B., Hullinger R., Dunleavy M., Knight D.A., Kunkel S.L., Uematsu S., Akira S., Hogaboam C.M. The protective role of TLR6 during experimental fungal asthma in mice is mediated by IL-23 and IL-17A. J. Clin. Invest., Nov 1: 121(11): 4420-32, 2011. PMCID: PMC3204826.

Matsuno, Y., Coelho A.L., Jarai G., Westwick J., Hogaboam C.M.  Notch signaling mediates TGF-beta1-induced EMT through the induction of Snai1.  Int. J. Biochem. Cell Biol., Epub ahead of print Feb 7, 2012.  PMID: 22330899.

Hogaboam C.M., Murray L., Martinez F.J.  Epigenetic mechanisms through which TLR9 drives IPF.  Proc. Am. Thorac. Soc. 9(3): 772-176, 2012.  PMID: 22802293.