Brown, Jessica C. S., PhD
- Microbial Pathogenesis
- Genetics, Microbial
- Antimicrobial Drug Discovery
- Infectious disease mechanisms (host-pathogen interaction)
- Departments: Pathology - Assistant Professor
- Divisions: Microbiology and Immunology
Academic Office Information
Emma Eccles Jones Medical Research Building
15 N Medical Dr E, Room: 5200B
Salt Lake City, UT
My lab’s goal is to explain why the complex network of interactions between a host and an opportunistic pathogen only sometimes results in a stable infection. I primarily use the fungus Cryptococcus neoformans as a model system. C. neoformans causes ~1 million infections and 600,000 deaths annually, most of which occur in patients with a compromised immune system. Despite near universal environmental exposure to C. neoformans, the vast majority of people do not exhibit any adverse health consequences. When C. neoformans does cause disease, it is extremely difficult to treat, commonly causing meningoencephalitis and requiring a year or more on toxic anti-fungal medications.
We investigate the infection process from the perspective of both the fungus and the host, including how C. neoformans interacts with and evades destruction by the host immune system. We are also identifying the genes which allow the fungus to be virulent and discovering their molecular mechanisms of action. Many of these genes are poorly conserved in traditional model organisms, so their characterization opens broad new opportunities to understand immunity and to design targeted, less toxic anti-fungal drugs.
Some of our research questions will include:
1) How does C. neoformans escape from its initial site of infection in the lungs and spread to the brain? What fungal and host genes are involved and how do the gene products interact?
2) How are the cell surface polysaccharides of C. neoformans involved in immune system evasion? How is the mix of these polysaccharides regulated? Are these pathways pathogen-specific, and can pathway members serve as drug targets?
We take a interdisciplinary approach spanning genetics, cell biology, microscopy, genomics, whole genome sequencing, gene expression analysis, and molecular biology in microbial culture, cell culture, and mouse infection model systems. The ultimate goal is to apply our biological knowledge to additional pathogenic fungi and facilitate new anti-fungal therapy development.
|Postdoctoral Fellowship||University of California, San Francisco
|Doctoral Training||Massachusetts Institute of Technology
- Wambaugh MA, Brown JCS (). High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method. J Vis Exp, 135, e57241.
- Denham ST, Verma S, Reynolds RC, Worne CL, Daugherty JM, Lane TE, Brown JCS (). Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system. Infect Immun, 86(3), e00662-17.
- Wambaugh MA, Shakya VPS, Lewis AJ, Mulvey MA, Brown JCS (). High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance. PLoS Biol, 15(6), e2001644.
- Chiaro TR, Soto R, Stephens WZ, Kubinak JL, Petersen C, Gogokhia L, Bell R, Delgado JC, Cox J, Voth W, Brown J, Stillman DJ, OConnell RM, Tebo AE, and Round JL (). A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med, 9(380), eaaf9044.
- Jarosz DF, Brown JC, Walker GA, Datta MS, Ung WL, Lancaster AK, Rotem A, Chang A, Newby GA, Weitz DA, Bisson LF, Lindquist S (). Cross-kingdom chemical communication drives a heritable, mutually beneficial prion-based transformation of metabolism. Cell, 158(5), 1083-93.
- Jarosz DF, Lancaster AK, Brown JC, Lindquist S (). An evolutionarily conserved prion-like element converts wild fungi from metabolic specialists to generalists. Cell, 158(5), 1072-82.
- Brown JC, Nelson J, VanderSluis B, Deshpande R, Butts A, Kagan S, Polacheck I, Krysan DJ, Myers CL, Madhani HD (2014 Nov 20). Unraveling the biology of a fungal meningitis pathogen using chemical genetics. Cell, 159(5), 1168-87.
- Butts A, Koselny K, Chabrier-Rosello Y, Semighini CP, Brown JC, Wang X, Annadurai S, DiDone L, Tabroff J, Childers WE Jr, Abou-Gharbia M, Wellington M, Cardenas ME, Madhani HD, Heitman J, Krysan DJ (2014). Estrogen receptor antagonists are anti-cryptococcal agents that directly bind EF hand proteins and synergize with fluconazole in vivo. mBio, 5(1), e00765-13.
- Brown JC, Madhani HD (2012). Approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling. PLoS Genet, 8(12), e1003168.
- Chun CD, Brown JC, Madhani HD (2011 Mar 17). A major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by Cryptococcus neoformans. Cell Host Microbe, 9(3), 243-51.
- Brown JC, Lindquist S (2009 Oct 1). A heritable switch in carbon source utilization driven by an unusual yeast prion. Genes Dev, 23(19), 2320-32.
- Edwards S, Li CM, Levy DL, Brown J, Snow PM, Campbell JL (2003 Apr). Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion. Mol Cell Biol, 23(8), 2733-48.
- Grossmann KF, Brown JC, Moses RE (1999 May 14). Cisplatin DNA cross-links do not inhibit S-phase and cause only a G2/M arrest in Saccharomyces cerevisiae. Mutat Res, 434(1), 29-39.
- Denham ST, Brown JCS (). Mechanisms of pulmonary escape and dissemination by Cryptococcus neoformans. [Review]. J Fungi (Basel), 4(1), 25.
- Enioutina EY, Teng L, Fateeva TV, Brown JCS, Job KM, Bortnikova VV, Krepkova LV, Gubarev MI, Sherwin CMT (). Phytotherapy as an alternative to conventional antimicrobials: Combating microbial resistance. [Review]. Expert Rev Clin Pharmacol, 10(11), 1203-14.
- Denham, ST, MA Wambaugh, and JCS Brown (). How environmental fungi cause a range of outcomes in susceptible hosts. [Review]. J Mol Biol.