Christopher Byron Brooke
390A Burrill Hall
601 South Goodwin Avenue
Urbana, IL 61801
Office: (217) 265-0991
Lab: (217) 244-4917
Mail to: B103 CLSL, MC-110
601 South Goodwin Avenue
Urbana, IL 61801
Host-Pathogen Interactions, Molecular Evolution, Molecular Immunology, Regulation of Gene Expression, Virology
Disease Research Interests
B.A. (Biology), Washington University, 2003
Ph.D (Microbiology & Immunology), University of North Carolina, 2010
Postdoctoral (Viral Immunology), Laboratory of Viral Diseases, NIAID, 2010-2015
Mechanisms of influenza virus adaptation
Influenza virus remains a major global health concern, despite the decades-long existence of a licensed vaccine. This ongoing threat is a direct function of the virus’ remarkable adaptability, which enables it to transmit within and between widely divergent host species while deftly evading herd immunity. Unfortunately, we still know very little about the specific mechanisms that facilitate influenza virus host adaptation, transmissibility, and immune escape. Defining these mechanisms is critical for understanding influenza pathogenesis, as well as for improving vaccines, therapeutics, and pandemic surveillance.
My laboratory is primarily focused on understanding how heterogeneity and collective interactions within influenza virus populations influence broader patterns of viral evolution and infection outcome. Influenza virus populations are enormously heterogeneous, and most viral particles carry a functionally incomplete set of gene segments and thus cannot replicate independently. Rather than serving as dead-end products, widespread co-infection in vivo allows these incomplete particles to replicate and exchange gene segments through complementation. Collective interactions between heterogeneous particles can have profound effects on the behavior of the population as a whole, and the outcome of infection. We and our collaborators are currently employing a wide range of approaches spanning molecular virology, cell biology, evolutionary biology, single cell microfluidics, bioinformatics, and mathematical modeling to better understand this crucial, under-explored area of virus biology.
We are also interested in understanding the genetics of influenza virus immune escape and transmission, with the overall goal of improving strategies for universal vaccination. The specific factors that govern the continual antigenic evolution of influenza virus within the human population remain poorly understood. We have developed improved methods for ultra-deep viral population sequencing that allow us to dissect the process of antigenic evolution within and transmit between hosts like never before.
Specific areas of study within the lab include:
Defining how patterns of viral heterogeneity and collective interactions within viral populations influence their evolutionary and pathogenic potential.
Defining the epistatic interactions between viral gene segments and determining how they influence viral evolution.
Using single-particle/single-cell analysis to examine how the interplay between viral and host heterogeneity shapes infection outcome.
Employing ultra-deep population sequencing methods to understand how influenza populations maintain fitness while evading host immunity.
Martin BE and Brooke CB. 2019. Flu shows the power of diversity. Cell. DOI: 10.1016/j.cell.2018.12.017.
Alnaji FG, Holmes JR, Rendon G, Vera JC, Fields CJ, Martin BE, and Brooke CB. 2018. Illumina-based sequencing framework for accurate detection and mapping of influenza virus defective interfering particle-associated RNAs. BioRxiv. Available from: https://doi.org/10.1101/440651.
Koelle K, Ferrell A, Brooke CB, and Ke R. 2018. Within-host infectious disease models accommodating cellular coinfection, with an application to influenza. BioRxiv. Available from: https://doi.org/10.1101/359067.
Gallagher ME, Brooke CB, Ke R, and Koelle K. 2018. Causes and Consequences of Spatial Within-Host Viral Spread. Viruses. DOI: 10.3390/v10110627.
Sun J and Brooke CB. 2018. Influenza A virus superinfection potential is regulated by viral genomic heterogeneity. mBio. DOI: 10.1128/mBio.01761-18.
Diefenbacher M, Sun J, and Brooke CB. 2018. The parts are greater than the whole: the role of semi-infectious particles in influenza A virus biology. Curr. Opin. in Virol. DOI: 0.1016/j.coviro.2018.07.002.
Kosik I, Ince WL, Gentles L, Oler AJ, Kosikova M, Angel M, Magadan J, Xie H, Yewdell JW*, and Brooke CB*. 2018. Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. PLOS Pathogens. DOI: 10.1371/journal.ppat.1006796. *Authors contributed equally • Selected by editors as a feature research article
Brooke CB. 2017. Population diversity and collective interactions during influenza virus infection. J. Virol. PMID: 28855247.
Brooke CB*, Ince WL*, Bennink JR, and Yewdell JW. 2014. Influenza A virus nucleoprotein selectively decreases neuraminidase gene segment packaging while enhancing fitness and transmissibility. PNAS. 111(47): 16854-16859. *Authors contributed equally
Brooke CB, Ince WL, Wrammert J, Ahmed R, Wilson PC, Bennink JR, and Yewdell JW. 2012. Most influenza A virions fail to express at least one essential viral protein. J. Virol. 87(6): 3155-62.
• Selected as Issue Highlight
• F1000 Prime Recommendation (A. Garcia-Sastre and A. Baum. f1000.com/prime/717983224)
• Commentary by Carl Zimmer (Influenza: Our Incompetent Enemy. National Geographic