Robert Cramer, Assistant Professor

Assistant Professor Fungal Pathogenesis Department of Veterinary Molecular Biology Montana State University PO Box 173610 Bozeman, MT 59717 Office: 406-994-7467 Lab: 406-994-7468 rcramer@montana.edu

Research Interests

PATHOGENESIS MECHANISMS OF THE OPPORTUNISTIC HUMAN FUNGAL PATHOGEN ASPERGILLUS FUMIGATUS

Current Research

Our laboratory is focused on elucidating the pathogenesis mechanisms of the opportunistic human fungal pathogen Aspergillus fumigatus (Af). Af causes invasive pulmonary aspergillosis (IPA) in immunocompromised patients and hypersensitivity type diseases such as Allergic Bronchopulmonary Aspergillosis in immunocompetent individuals. Patients that acquire IPA have often undergone solid organ or bone marrow transplants for various cancers. Patients that acquire invasive Aspergillus infections face a grim prognosis with mortality rates approaching 90% depending on the patient population. Given the degree of similarity between human and fungi, current treatment options for patients are limited. Thus, we urgently need to better understand how Aspergillus fumigatus is able to colonize, infect, and cause disease in immunocompromised and immunocompetent patients. To gain this understanding, we utilize molecular biology, functional genomics, bioinformatics, immunology, and animal models to identify genes and biochemical pathways that allow the fungus to cause disease in immunocompromised and immunocompetent mammals. Currently, we are focusing on three attributes of the fungus that we hypothesize allows it to cause invasive and chronic disease: tolerance to low oxygen conditions (hypoxia) found in vivo during infection, production of a unique carbohydrate (trehalose) that may protect the fungus from environmental stresses found in vivo, and production of low molecular weight toxins which may exacerbate disease pathophysiology. The field of medical mycology is a rapidly expanding field that allows students to explore and learn basic and advanced concepts in infectious disease, molecular biology, immunology, and genomics research.

In addition, our laboratory has recently begun research on the emerging honeybee pathogen, Nosema ceranae. Nosema species are microsporidians, a group of organisms closely related to the fungi. Nosema species are often obligate pathogens that rely on their host for energy production and growth. We are currently studying several aspects of Nosema diseases in honeybees including: development of an in vitro infection model for spore propagation and host-pathogen interaction studies, identification of fumagillin alternative compounds for the prevention of Nosema diseases, and development of a quantitative real-time PCR assay for the identification of Nosema infections in beekeeping operations.

Education

• NIH/NIAID, Molecular Mycology and Pathogenesis Training Program 2004 – 2007, Post-Doctoral Fellowship, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
• Doctor of Philosophy, Plant Pathology 2001-2004. Department of Bioagricultural Sciences and Pest Management, Colorado State University, Fort Collins, CO.
• Master of Sciences, Plant Breeding/Genetics 1999-2001. Department of Soil and Crop Sciences, Colorado State University, Fort Collins, CO.
• Bachelor of Arts, Biology 1995-1999, Lawrence University Appleton, Wisconsin

Professional Experience

• 2007-Current  Assistant Professor Fungal Pathogenesis, Montana State University, Department of Veterinary Molecular Biology.
• 2004 – 2007 NIH/NIAID, Molecular Mycology and Pathogenesis Training Program, Post-Doctoral Fellowship, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
• 2001 – 2004 Graduate Research Assistant Colorado State University, Department of Bioagricultural Sciences and Pest Management.
• 2000-2001 Litzenberger Fellowship, Colorado State University, Department of Soil and Crop Sciences.

Honors and Awards

• NIH/NIAID, Duke University Molecular Mycology and Pathogenesis Training Program Post-Doctoral Fellowship June 2004 - 2007
• Ralph Baker Research Excellence Award, Department of Bioagricultural Sciences and Pest Management, Colorado State University, December 2003.
• Competitive Travel Grant, 22nd International Fungal Genetics Conference, Asilomar, California, March 2003
• Monty and Jeanice Harrison Outstanding Student of Plant Pathology Scholarship

          Department of Bioagricultural Sciences and Pest Management, Colorado State University, December 2002

• The Eddie Echandi Award, American Phytopathological Society, APS Foundation May 2002
• Colorado State University Research Excellence Grant, Graduate School, Colorado State University, May 2002
• R. Ralph Baker Research Excellence Award, Department of Bioagricultural Sciences and Pest Management, Colorado State University, October 2001
• Colorado Institute of Biotechnology travel award for International Fungal Genetics Conference at Asilomar, California March 2001
• Albert K Dobrenz Award for presentation of graduate student paper judged to be outstanding at the Western Society of Crop Science Annual Meeting, June 2000
• Litzenberger Graduate Fellowship for MS Thesis research at Colorado State University,  Department of Soil and Crop Sciences, January 2000.

Selected Publications

1. Willger, S.D., Puttikamonkul, S., Kim, K.H., Burritt, J.B., Grahl, N., Metzler, L.J., Barbuch, R., Bard, M., Lawrence, C.B., Cramer, R.A. 2008. A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathogens, 4, e1000200
2. Grahl, N. and Cramer, R.A. 2009. Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi? Medical Mycology, May 22nd, 1-16.
3. Willger, S.D., Grahl, N., and Cramer, R.A. 2008. Aspergillus fumigatus metabolism: Clues to mechanisms of in vivo fungal growth. Medical Mycology, Feb. 27th, EPub Ahead of Print.
4. Pinchai, N., Perfect, B.Z., Juvvadi, P.R., Fortwendel, J.R., Cramer, R.A., Asfaw, Y.G., Heitman, J., Perfect, J.R., Steinbach, W.J. 2009. The Aspergillus fumigatus Calcipressin CbpA is involved in hyphal growth and calcium homeostasis. Eukaryotic Cell, 8:511-519.
5. Cramer, R.A., Perfect, B.Z., Pinchai, N., Park, S., Perlin, D.S., Asfaw, Y., Heitman, J., Perfect, J.R., and Steinbach, W.J. 2008. The calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of Aspergillus fumigatus. Eukaryotic Cell, 7:1085-1097.
6. Perrin, R.M., Fedorova, N.D., Bok, J.W., Cramer, R.A., Wortman, J.R., Kim, H.S., Nierman, W.C., and Keller, N.P. 2007. Transcriptional regulation of chemical diversity in Aspergillus fumigatus. PLoS Pathogens, 3:1-10.
7. Steinbach, W.J., Cramer, R.A., Perfect, B.Z., Henn, C., Nielsen, K., Heitman, J., Perfect J.R. 2007. Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy, 51:2979-81.
8. Steinbach, W.J., Reedy, J., Cramer, R.A., Perfect, J.R., and Heitman, J. 2007. Harnessing calcineurin as an anti-infective target in pathogenic fungi. Nature Reviews, 5:418-30.
9. Cho, Y., Cramer, R.A., Kim, K.H., Mitchell, T.K., Figuli, P., Pryor, B., and Lawrence, C.B. 2007. A pathogenicity factor MAP kinase has dual functions in controlling hydrolytic enzyme coding genes in Alternaria brassicicola. 2007. Fungal Genetics and Biology, 44: 543-553.
10. Kim, K.H., Cho, Y., La Rota, C., Cramer, R.A., and Lawrence, C.B. Functional analysis of the Non-ribosomal peptide synthetase ABNPS2 reveals a role in conidial cell wall construction. 2007. Molecular Plant Pathology, 8:23-29.
11. Cramer, R.A., Stajich, J.E., Yamanaka, Y., Dietrich, F.S., Steinbach, W.J., and Perfect, J.R. 2006. Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus. Gene, 383:24-32.
12. Cramer, R.A., Gamcsik, M.P., Bookings, R., Najvar, L.K., Kirkpatrick, W.R., Balibar, C, Graybill, J.R., Patterson, T.F., Perfect, J.P., Abraham, S., and Steinbach, W.J. 2006. Disruption of a non-ribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryotic Cell, 5:972-80. Featured in Faculty of 1000 Biology http://www.f1000biology.com/article/id/1032648/
13. Steinbach, W.J.*, Cramer, R.A.*, Perfect. B.Z., Asfaw, Y.G., Sauer, T.C., Najvar, L.K., Kirkpatrick, W.J., Patterson, T.F., Benjamin, D.K., Heitman, J., and Perfect, J.R. 2006. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryotic Cell, 5:1091-1103. *Authors Contributed Equally to this manuscript. Featured in ASM Microbe Journal September 2006.

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