Allen Harmsen, Professor

Veterinary Molecular Biology P.O. Box 173610 Montana State University Bozeman, MT 59717 (406) 994-7626 aharmsen@montana.edu

Research Interests

Research in the Harmsen Lab encompasses the areas of Pulmonary Immunology and Immunopathology. The lung is extremely susceptible to infection because of the constant deposition of potential pathogens in the airways that results from breathing contaminated air. Thus, the lung must respond to these pathogens quickly and intensely to avoid infection. Although these host immune and inflammatory responses usually are successful in preventing infection, these processes can also be damaging to the host. This is especially a problem for the lung because the delicate lace-like structure of lung tissue is easily damaged. In addition, misguided immune responses to inhaled noninfectious antigens, such as allergens, can directly cause serious diseases such as asthma and bronchitis. The major goal of our research is to better understand how the lung immune responses can resist infections and yet limit "collateral" host damage caused by the immune response. In the process of studying these mechanisms of resistance and tissue damage, our lab utilizes animal models of disease.  These include mouse models of influenza, Pneumocystis murina pneumonia,  Coxiella burnetii, and  Streptococcus as well as bovine models of viral and bacterial pneumonia.

Education

• Postdoc Vermont Lung Center University of Vermont 1980-81
• Ph.D. Immunobiology Iowa State University 1980
• B.S. Biology University of Wisconsin 1974

Professional Experience

• 2006-present Professor, Veterinary Molecular Biology, Montana State University, Bozeman, MT
• 2001-2005 Head, Veterinary Molecular Biology, Montana State University, Bozeman, MT
• 1998-present Visiting Scientist, Harvard School of Public Health, Boston, MA
• 1995-present Adjunct Professor, Department of Pediatrics, Microbiology and Immunology University of Rochester School of Medicine and Dentistry, Rochester, NY
• 1998-2001 Full Member, Trudeau Institute, Inc., Saranac Lake, NY
• 1991-1997 Associate Member, Trudeau Institute, Inc., Saranac Lake, NY
• 1987-1991 Assistant Member, Trudeau Institute, Inc., Saranac Lake, NY
• 1985-1987 Associate Scientist, Cell Toxicology, Lovelace Inhalation Toxicology Research Institute, Albuquerque, NM
• 1981-1985 Assistant Professor of Biology, Biology Department, New Mexico Institute of Mining and Technology, Socorro, NM
• 2003-present  Affiliate Professor, Department of Immunology, University of Washington School of Medicine, 
• 2004-present     Member, AAI Veterinary Immunology Committee
• 2008-present   Chartered Member NIH-AOIC Study Section

Extramural Grant Activity

• P20 RR020185-01 NIH COBRE (Harmsen- PI) 10/1/04 - 7/31/09 Center for Immunotherapies to Zoonotic Diseases.  The goal of this COBRE is to develop a Center of Research at Montana State University that will make significant scientific contributions to the knowledge of the pathogenesis of zoonotic diseases.

• RO1 (HL55002) 4/1/90-3/31/10 NIH/NHLBI Reconstitution of Immunity to Pneumocystis in SCID Mice.                    Major goal is to determine mechanisms of resistance to P. carinii in mice and to supply P. carinii organisms and infected mice to other projects in the program

• R01 (HL55002) (Harmsen – PI) 4/1/99-3/31/10  NIH/NHLBI Reconstitution of Immunity to Pneumocystis in SCID Mice

  The major goal is to determine mechanisms of resistance to P. carinii in mice.

  Role:  PI

• R01 (HL094233) (Harmsen-PI) 4/01/09-3/31/14 NIH/NHLBI  CD4 T cell-mediated lung damage in Pneumocystis pneumonia

  The major goal of this project is to identify cytokines, cells, cell interactions, and cell functions that are responsible for CD4 T cell-mediated lung damage in Pneumocystis pneumonia.

  Role: PI

• P20 RR16455 (Harmsen-PI) 7/1/04-6/30/14 INBRE-BRIN “Montana Network of Biomedical Research Resources" Director of Infectious Disease:  Allen G. Harmsen, Ph.D.                                                                                       The major goal of this project is to provide assistance and guidance in the development of the biomedical research capabilities and professional growth of project leaders across the state and to work with these leaders as a collaborator. Role:PI 

• P20 RR020185 (Quinn-PI) 9/29/04-7/31/14  NIH  (COBRE) "Center for Immunotherapies to Zoonotic Diseases"        The goal of this project is to develop a Center of Research at Montana State University that will make significant scientific contributions to the knowledge of pathogenesis of zoonotic diseases.                                                       Role: Mentor

• P01 AT004986-01NIH/NCCAM (Jutila-PI) 10/1/08-10/30/13 NCCAM-NIH Title:CAMS as countermeasures against infectious and inflammatory disease; Animal core                                                                                                 The major goal of this project is to supply all project investigators with immunocompetent and transgenic mice to discern mechanisms of action using their CAMs.  In addition, this core provides for young investigators to test their CAMs in novel infectious disease models including influenza, rotavirus, Brucella melitensis, Coxiella burnetii, Mycobacterium avium subsp. paratuberculosis, methicillin-resistant Staphylococcus aureus as well as autoimmune diseases, including dextran sodium sulfate (DSS)-induced colitis and collagen II-induced arthritis                         Role:Core Co-Director

• 1-U54 AI065357-01 RMRCE (Belisle, PI) 5/1/09-4/30/10  NIH -RMRCE

  Developmental Project Grant:  Development of a therapy to attenuate lung damage in Coxiella infection.

  The goal of this project is to develop immunotherapies to lung pathogens utilizing protein cages to accelerate the immune response and reduce lung damage.                                                                                                                

  Role: Project leader

Service, Honors and Awards

Phi Kappa Phi, Graduate Honors Society, Iowa State University NRSA Postdoctoral Fellowship, University of Vermont Member, Scientific Advisory Board of Parker B. Francis Family Foundation Member of NIH-ARRE Study Section Member Executive Board, Trudeau Institute Member, National Academy of Sciences, Committee on Biological Markers of Environmental Exposure to Toxic Substances

Selected Publications

• Wiley, J.A., R. Geha, and A.G. Harmsen. 1997. Exogenous CD40 ligand induces a pulmonary inflammatory response. J. Immunol. 158:2932-2938.
• Garvy, B.A., F. Gigliotti, and A.G. Harmsen. 1997. Neutralization of IFN-? exacerbates Pneumocystis-driven interstitial pneumonitis following bone marrow transplantation in mice. J. Clin. Invest. 99:1637-1644.
• Gigliotti, F., B.A. Garvy, C.G. Haidaris and A.G. Harmsen. 1998. Recognition of Pneumocystis carinii antigens by local antibody secreting cells following resolution of P. carinii in mice. J. Infect. Dis. 178:235-242.
• Gigliotti, F., J.A. Wiley and A.G. Harmsen. 1998. Immunization with Pneumocystis carinii gpA is immunogenic but not protective in a mouse model of P. carinii pneumonia. Infect. Immun. 66:3179-3182.
• Simpson- Haidaris, P.J., M.A. Courtney, T.W. Wright, R. Goss, A.G. Harmsen and F. Gigliotti. 1998. Induction of the acute phase reactant fibrinogen in the lung epithelium during Pneumocystis carinii pneumonia. Infect. Immun. 66:4431-4439.
• Cerwenka, A., T. Morgan, A.G. Harmsen and R. Dutton. 1999. Migration kinetics and final destination of Tc1 and Tc2 CD8 effector cells predicts protection against pulmonary virus infection. J. Exp. Med. 189:423-434.
• Wiley, J.A. and A.G. Harmsen. 1999. Bone marrow-derived cells are required for the induction of a pulmonary inflammatory response mediated by CD40-ligation. Am. J. Pathol. 154:919-926.
• Wright, T.W., C.J. Johnston, A.G. Harmsen and J.N. Finkelstein. 1999. Chemokine mRNA profiles in the lungs of mice infected with Pneumocystis. Infec. Immun. 67:3452-3460.
• Wright, T.W., F. Gigliotti, J.N. Finkelstein, J.T. McBride, C. An and A. G. Harmsen. 1999. Immune-mediated Inflammation Directly Impairs Pulmonary Function Contributing to the Pathogenesis of Pneumocystis Pneumonia. J. Clin. Invest. 104:1307-1317.
• Stehle, S.E., R.A. Rogers, A.G. Harmsen, and R.A. Ezekowitz. 2000. A soluble manose receptor immunoadhesin enhances phagocytosis of Pneumocystis carinii by human polymorphonuclear leukocytes in vitro. Scand. J. Immunol. 52:131-137.
• Fraser, I.P., K. Takahashi, H. Koziel, B. Fardin, A.G. Harmsen and R.A.B. Ezekowitz. 2000. Pneumocystis carinii enhances soluble mannose receptor production by macrophages. Microbes and Infect. 2:1305-1310.
• Wiley, J.A., A. Cerwenka, J.R. Harkema, R.W Dutton, and A.G. Harmsen. 2001. Production of IFN gamma by influenza HA-specific CD8 effector T cells influences the development of pulmonary immunopathology. Am. J. Pathol. 158:119-130.
• Wright, T.W., R.H. Notter, A. Wang, A.G. Harmsen, and F. Gigliotti. 2001. Pulmonary inflammation disrupts surfactant function during Pneumocystis carinii Pneumonia. Infect. Immun. 69:758-764.
• Hogan, R.J., E.J. Usherwood, W. Zhong, A.D. Roberts, R.W. Dutton, A.G. Harmsen, and D.L. Woodland, 2001. Activated antigen-specific CD8+ T cells persist in the lungs following recovery from respiratory virus infections. J. Immunol. 166:1813-1822.
• Herzyk, D.J., E.R. Gore, R. Polsky, K.L. Nadwodny, C.C. Maier, S. Liu, T.K. Hart, A.G. Harmsen and P.J. Bugelski. 2001. Immunomodulatory effects of anti-CD4 antibody in host resistance against infections and tumors in human CD4 transgenic mice. Infect. Immun. 69:1032-1043.
• Wiley, J.A., R.J. Hogan, D.L. Woodland, and A.G. Harmsen. 2001. Antigen-specific CD8 T cells persist in the upper respiratory tract following influenza virus infection. J. Immunol. 167:3293-3299.
• Partida-Sanchez, S., D. Cockayne, S. Monard, E.L. Jacobson, B. Garvy, K. Kusser, M. Howard, A.G. Harmsen, T.D. Randall, and F.E. Lund. 2001. Neutrophils require CD38 for chemotaxis, capacitative Ca2+ entry and bacterial clearance. Nature Medicine 7:1209-16.
• Harmsen. A.G., K. Kusser, L. Hartson, M. Tighe, M.J. Sunshine, Jonathon D. Sedgwick, Y. Choi, D.R. Littman and T. Randall. 2002. Organogenesis of Nasal Associated Lymphoid Tissue (NALT) occurs through mechanisms that bypass the requirement for lymphotoxin-a and retinoic acid receptor-related orphan receptor-gamma, (ROR gamma). J. Immunol. 168:986-990.
• Gigliotti, F., C.G. Haidaris, T.W. Wright, and A.G. Harmsen. Passive intranasal monoclonal antibody prophylaxis against murine Pneumocystis carinii pneumonia. Infect. Immun. 2002 Mar;70(3):1069-74.
• Woodland D, Ely K, Crowe S, Tighe M, Brennan J, Harmsen A, Cauley L. 2002. Antiviral memory T-cell responses in the lung. Microbes Infect. 10:1091.
• Roman E, Miller E, Harmsen A, Wiley J, von Andrian U, Huston G, Swain S. 2002. Primary CD4 T cell response generates heterogeneous CD4 effector cells differing in phentotype, migration and function. J. Exp. Med. 196 (7): 957-968.
• Qureshi, M.H., A.G. Harmsen, B.A. Garvey. 2003. IL-10 Modulates Host Responses and Lung Damage Induced by Pneumocystis carinii Infection. J. Immunol. 170:1002-9.
• An, C.L., F. Gigliotti, A.G. Harmsen. 2003. Exposure of immunocompetent adult mice to Pneumocystis muris by co-housing: growth of P. muris and host immune response. Infect. Immun. 71:2065-70.
• Chen W., J.A. Harp, A.G. Harmsen . 2003. Cryptosporidium parvum infection in gene-targeted B cell-deficient mice. J. Parasitol. 89:391-3·
• Gigliotti, F., T. Wright, A. G. Harmsen. 2003. Characterization of transmission of Pneumocystis carinii through immunocompetent BALB/c mice. Infect. Immun. 71:3852-6.
• Steve D. Swain, Sena J. Lee, Michel C. Nussenzweig, A. G. Harmsen. 2003. Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility to Pneumocystis carinii Infection In Vivo. Infection and Immunity. 71:6213-21.
• Steele, C., L. Marrero, S. Swain, A.G. Harmsen, M. Zheng, G. D. Brown, S. Gordon, J. E. Shellito, J. K. Kolls. 2003. Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor. J. Exp Med. 1:198 (11): 1677-88.
• Swain, S.D., T.W. Wright, P.M. Degel, F. Gigliotti, A.G. Harmsen. 2004. Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice. Infect. Immun. 72:5722-5732.
• Silflow, R.M., P.M. Degel, and A.G. Harmsen. 2005. Bronchoalveolar immune defense in cattle exposed to primary and secondary challenge with bovine viral diarrhea virus. Vet. Immunol. Immunopathol.
• Meissner, N.N., S. Swain, M. Tighe, A. Harmsen and A.G. Harmsen. 2005. Role of type I interferons in pulmonary complications of Pneumocystis murina infection. J. Immunol. In Press.

• Wiley, JA, MP Tighe, and AG Harmsen. 2005. Upper Respiratory Tract Resistance to Influenenza Infection Is Not Prevented by the Absence of either NALT or Cervical Lymph Nodes. J. Immunol. 175: 3186-96.

• Meissner, NN, FE Lund, S Han, and AG Harmsen. 2005. CD8 T-cell mediated lung damage in response to the extracellular pathogen Pneumocystis is dependent on MHC I expression by radiation resistant cells.  J. Immunol. 175:8271-79.

• Crowe, SR, SC Miller, DM. Brown,  RW Dutton, AG Harmsen, FE Lund, TD Randal, SL Swain, DL Woodland. 2006. Uneven distribution of MHC Class II epitopes within the influenza virus. Vaccine. 24: 457-67.

• Swain, SD, NN Meissner, AG Harmsen. 2006. CD8 T cells modulate CD4 T cell and eosinophil-mediated pulmonary pathology in Pneumocytis pneumonia in B-cell-deficient mice. Am. J. Pathol. 168: 466-75.

• Flenniken, ML, DA Willits, AL Harmsen, LO Liepold, AG Harmsen, MJ Young, and T Douglas. 2006. Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture. Chem. Biol. 13:161-70.

• Bruckner, L, F Gigliotti, T Wright , A Harmsen, R H Notter, P Chess, Z Wang, and J Finkelstein. 2006. Pneumocystis carinii Infection Sensitizes the Lung to Radiation-Induced Injury after Syngeneic Marrow Transplantation: Role of CD4+ T-Cells. Am. J. Physiol.-Lung Cell. Mol. Physiol. 290:1087-96.

• Hall-Stoodley, L, G Watts, J Crowther, A Balagopal, J Torrelles, J Robinson-Cox, R Bargatze, A Harmsen, E Crouch and L Schlesinger. 2006. Mycobacterium tuberculosis binding to human Surfactant Poteins A and D, fibronectin and small airway epithelial cells under shear. Infect. Immun. 74:3587-96.

• Bonnett, CR, EJ Cornish, AG Harmsen, and JB Burritt. 2006. Early neutrophil recruitment and aggregation in the murine lung inhibit germination of Aspergillus fumigatus conidia. Infect. Immun. 74:6528-39.

• Moyron-Quiroz, JE, J Rangel-Moreno, L Hartson, MP Tighe, KD Klonowski, L Lefrancois, LS Caughly, AG Harmsen, FE Lund, and TD Randall. 2006. Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs. Immunity. 4:643-54.

• McNamee, LA and AG Harmsen. 2006. Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection. Infect. Immun. 74:6707-21.

• Rutkowski, MR and AG Harmsen. 2007. Trichomonas foetus: Pathogenesis of acute infection in normal, estradiol-treated, and stressed mice. Exp. Parasitol. 115: 143-59.

• Rutkowski, MR, LA McNamee and AG Harmsen. 2007. Neutrophils and INOS are critical for early resistance to the establishment of Tritrichomonas foetus infection. J. Parasitol. Jun;93(3):562-74.

• Kaiser, CR, ML Flenniken, AG Harmsen, AL Harmsen, M A Jutila, T Douglas, and M J Young. 2007. Biodistribution studies of protein cage nanoparticles demonstrate broad tissue distribution and rapid clearance in vivo. International J. Nanomedicine 2007;2(4):715-33

• Meissner, NN, M Rutkowski, A Harmsen, S Hann, AG Harmsen. 2007. Type I IFN-signaling and B cells maintain hematopoiesis during Pneumocystis infection of the lung. J. Immunol.178 (10) 6604-15

• Swain S, S Han, A Harmsen, K Shampeny, and AG Harmsen 2007. Pulmonary Hypertension Can Be A Sequela Of Prior Pneumocystis Pneumonia. Am J Pathol. 171:790-799.

• Wiley, J.A. and Harmsen AG 2008. Pneumocystis Infection Enhances Antibody-Mediated Resistance to a Subsequent Influenza Infection. J Immunol 180: 5613-24. NIHMS58413.

• Haynes, J.R., Dokken L., Wiley J.A., Cawthon A.G., Bigger J., Harmsen A.G., Richardson C. 2009 Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge. Vaccine27(4): 530-41.

• King, Q. O., B. Lei, and A. G. Harmsen. 2009. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection following Influenza Infection. J. Infect. Dis.  In Press.

• Pittet, Lynnelle A., Hall-Stoodley ,Luanne, Rutkowski Melanie R., Harmsen ,Allen G. 2009. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae. Am Journal of Respiratory Cell and Molecular Biology. In Press.

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