Robert Cramer, Assistant Professor
Assistant Professor Fungal Pathogenesis
Immunology & Infectious Diseases
Montana State University
PO Box 173610 Bozeman, MT 59717
PATHOGENESIS MECHANISMS OF THE HUMAN FUNGAL PATHOGEN ASPERGILLUS FUMIGATUS
Our laboratory is focused on elucidating pathogenesis mechanisms of the human fungal pathogen Aspergillus fumigatus (Af). Af is a filamentous fungus, or mold, and 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 high mortality rates ranging from 30%-90% depending on the patient population and available treatment options. Given the degree of genetic similarity between humans 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. As modern medical advances continue to increase the number of patients susceptible to invasive fungal infections, increasing successful outcomes will depend on new insights into fungal pathogenesis mechanisms provided by basic and translational research.
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 and regulation of ergosterol biosynthesis, the fungal cholesterol equivalent and current antifungal drug target. 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.
Finally, our laboratory has recently begun research on the emerging honeybee fungal like 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: identification of fumagillin alternative compounds for the prevention of Nosema diseases, understanding the infection structure, the polar tube, of N. ceranae and how it interacts with cells of the honeybee, and exploring potential virus-fungal relationships in honeybee health.
- NIH/NIAID, Molecular Mycology and Pathogenesis Training Program, Post-Doctoral Fellowship, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC.
- Doctor of Philosophy, Molecular Mycology, Department of Bioagricultural Sciences and Pest Management, Colorado State University, Fort Collins, CO.
- Master of Sciences, Plant Breeding and Mycology Department of Soil and Crop Sciences, Colorado State University, Fort Collins, CO.
- Bachelor of Arts, Biology, Lawrence University Appleton, Wisconsin
- 2007-Current Assistant Professor Fungal Pathogenesis, Montana State University, Department of Immunology & Infectious Diseases.
- 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.
Extramural Grant Activity
- R01 AI 81838-01 NIH/NIAID 08/15/2009 - 08/14/2013 "Hypoxia Adaptation and Fungal Virulence in Aspergillus fumigatus"
- 2P20RR020185-06 NCRR-COBRE 08/01/2009 - 07/31/2011 "Role of Alcohol Fermentation in Aspergillus fumigatus pathogenesis"
Selected Publications (of 32)
- Grahl, N., Puttikamonkul, S., Macdonald, J.M., Gamcsik, M.P., Ngo, L.Y., Hohl, T.M., and Cramer, R.A. 2011. In vivo hypoxia and a fungal alcohol dehydrogenase influence the pathogenesis of invasive pulmonary aspergillosis. PLoS Pathogens, 7 (7), PMID: 21811407
- Blatzer, M*., Barker, B.M.*, Willger, S.D., Beckmann, N., Blosser, S.J., Cornish, E.J., Mazurie, A., Grahl, N., Haas, H.*, Cramer, R.A.* 2011. SREBP coordinates iron and ergosterol biosynthesis homeostasis to mediate triazole and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genetics, In Press.
- Blosser, S.J. and Cramer, R.A. 2011. SREBP Dependent Triazole Susceptibility in Aspergillus fumigatus is Mediated Through Direct Transcriptional Regulation of erg11Alcyp51A. Antimicrobial Agents and Chemotherapy, In Press.
- Feng, X., Krishnan, K. Richie, D.L., Aimanianda, V., Hartl, L., Grahl, N., Powers-Fletcher, M.V., Zhang, M., Fuller, K.K., Nierman, W.C., Lu, L.J., Latge, J.P., Woollett, L., Newman, S.L., Cramer, R.A., Rhodes, J.C., and Askew, D.S. 2011. HacA independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in the fungal pathogen Aspergillus fumigatus. PLoS Pathogens, Oct;7(10):e1002330.
- Cramer, R.A., Rivera, A., and Hohl, T. 2011. Immune responses against Aspergillus fumigatus: What have we learned? Current Opinion in Infectious Disease, 24:315-22. PMID: 21666456
- Li, H., Barker, B., Grahl, N., Puttikamonkul, S., Bell, J.D., Craven, K.D., and Cramer, R.A. 2011. The small GTPase RacA mediates intracellular reactive oxygen species production, polarized growth, and virulence in the human fungal pathogen Aspergillus fumigatus. Eukaryotic Cell, 10:174-86. PMCID: PMC3067399
- Puttikamonkul, S., Willger, S.D., Grahl, N., Perfect, J.R., Movahed, N., Bothner, B., Park, S., Paderu, P., Perlin, D.S., and Cramer, R.A. 2010. Trehalose-6-Phosphate Phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus. Molecular Microbiology, 77:891-911. PMCID: PMC2954268
- Wezensky, S.J., and Cramer, R.A. 2010. Implications of hypoxia microenvironments during invasive pulmonary aspergillosis. Medical Mycology Apr 2011, Vol. 49, No. S1: S120-S124. PMCID: PMC2951492
- Kim, K.H, Willger, S.D., Park, S.W., Puttikamonkul, S., Grahl, N., Cho, Y., Mukhopadhyay, B., Cramer, R.A.* , Lawrence, C.B.* 2009. TmpL, a transmembrane protein is required for oxidative stress homeostasis and virulence in plant and animal fungal pathogens. PLoS Pathogens, 5(11) *Joint Corresponding Authors. PMCID: PMC2766074
- Grahl, N. and Cramer, R.A. 2009. Regulation of hypoxia adaptation: An overlooked virulence attribute of pathogenic fungi? Medical Mycology, 47:1-16 PMCID: PMC2898717.
- 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 steroloregulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathogens, Nov 4(11). PMCID: PMC2572145