Elke Mühlberger

Check out the Mühlberger lab webpage!

I have a long-standing research interest in studying highly pathogenic hemorrhagic fever viruses, including Ebola and Marburg viruses which belong to the filovirus family. Filoviruses cause a severe disease in humans with high case fatality rates. Due to the high pathogenicity of these viruses, they are classified as biosafety level 4 (BSL-4) pathogens. My lab studies different aspects of the filovirus infection cycle. One focus of our work is to dissect the mechanisms of filovirus genome replication and transcription with the goal to identify determinants of virulence. This includes work on Lloviu virus, a new member of the filovirus family, whose pathogenicity in humans is not known. Tools we use for this work include minigenome systems and recombinant viruses.

Another focus of our research is centered around the host response to filovirus infection. To mimic the events in infected patients, we mainly use human primary cells for our infection studies. This includes macrophages and monocyte-derived dendritic cells isolated from blood, as well as human immune and liver cells generated from induced pluripotent stem cells (iPSC). The iPSC-derived infection platforms are developed in collaboration with tissue engineers at BU’s Center for Regenerative Medicine (CReM). We use these platforms to analyze the host response to filovirus infection, including inflammatory signatures, cell damage and antiviral defense mechanisms. The information we obtain from these studies will help us to determine virulence factors and identify targets for antiviral therapeutics.

Based on our experience in studying emerging viral diseases, the Mühlberger lab recently joined the efforts to control the COVID-19 pandemic by providing virology service to members of the research community who do not have access to high containment space. We are currently performing SARS-CoV-2 infection studies in the NEIDL high containment facility for more than 20 investigators with highly diverse research interests, including antiviral drug screening, tissue engineering, molecular imaging, droplet stability, omics studies, and host response mechanisms.

Selected Publications

1. Hekman, R. M., Hume, A. J., Goel R. K., Abo, K. M., Huang, J., Blum, B. C., Werder, R. B., Suder, E. L., Paul, I., Phanse, S., Youssef, A., Alysandratos, K. D., Padhorny, D., Ojha, S., Patten, J. J., Villacorta-Martin, C., Bolzan, D., Perea-Resa, C., Bullitt, E., Hinds, A., Tilston-Lunel, A., Varelas, X., Braunschweig, U., Kwan, J. H., McComb, M., Basu, A., Saeed, M., Perissi, V., Burks, E. J., Wolozin, B. L., Layne, M. D., Blencowe, B. J., Wuchty, S., Lyons, S. M., Kozakov, D., Cifuentes, D., Connor, J. H., Davey, R., Blower, M., Kotton, D. N.^#, Wilson, A. A.^#, Mühlberger, E.^#, Andrew Emili, A.^#. 2020. Systems Level Survey of Actionable Cytopathogenic Host Responses of Human Lung Alveolar Type 2 Cells to SARS-CoV-2 Infection. Molecular Cell, S1097-2765(20)30828-5. PMID: 33259812.
2. Huang, J., Hume, A.J., Abo, K.M., Werder, R.B., Villacorta-Martin, C., Alysandratos, K.D., Beermann, M.L., Simone-Roach, C., Olejnik, J., Suder, E.L., Bullitt, E., Hinds, A., Sharma, A., Bosmann, M., Wang, R., Hawkins, F., Burks, E.J., Saeed, M., Wilson, A.A., Mühlberger, E., Kotton, D.N. SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response.  Cell Stem Cell. 2020 Sep 18:S1934-5909(20)30459-8. PMID: 32979316.
3. Deflubé LR, Cressey TN, Hume AJ, Olejnik J, Haddock E, Feldmann F, Ebihara H, Fearns R, Mühlberger E. Ebolavirus polymerase uses an unconventional genome replication mechanism. Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8535-8543 PMID: 30962389.