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Jessica Brown

Associate Professor of School of Biological Sciences

Pathogenesis, Fungal Genetics, Host-Pathogen Interaction



Molecular Biology Program


B.A. Pomona College

Ph.D. Massachusetts Institute of Technology



Humans constantly interact with microbes in the environment, yet these organisms rarely cause disease. Among the 3-10+ million species in the fungal kingdom, only a few hundred species are capable of causing human disease and only a few dozen routinely do so. The environmental systemic human fungal pathogens also do not spread person-to-person, suggesting that the patient is an evolutionary dead end for the fungus and therefore that selective pressure for pathogenicity is from the environment. The Brown lab is interested in three main questions relating to fungal pathogenesis:

How does a disseminating fungal pathogen establish and cause disease within a mammalian host?

The environmental pathogen Cryptococcus neoformans causes severe, disseminated disease in patients with compromised immune systems, particularly low CD4+ T cell levels. In the environment, C. neoformans is associated with pigeon guano, although it does not appear to colonize or cause disease in pigeons. We are interest in how C. neoformans adapts to the guano environment, spreads to and survives in mammalian lungs, then escapes from the lungs and disseminates to the brain. Along the way, C. neoformans cells change shape and size, adjust to dramatically different environmental conditions, and must evade host immune responses. We are interested in fungal factors involved in these processes and how fungi manipulate the host to these ends.

How can we improve treatment of systemic fungal infections?

Systemic fungal infections are notoriously difficult to treat and limited by a paucity of approved drugs. Historically strategies for developing new antifungal treatments focus either on identification of new antifungal compounds or repurposing of existing drugs by identifying antifungal activity. We take a third approach: identifying combination therapies by determining how existing antifungal drugs interact with drugs approved for other diseases, then elucidating the molecular processes underlying these interactions so they can be exploited to improve antifungal treatments. These new treatments are then relatively economic for patients, since they consist of off-patent drugs. In addition, patients with fungal infections often have complicated drug treatment regimes. Some of these cause unintentional interactions, so understanding the biology and networks underlying these interactions is necessary for preventing treatment complication.

How do fungi adapt to a changing global climate and do those adaptations increase pathogenicity?

Mammalian body temperature is thought to be a major block to fungal pathogenesis. However, we do not think that temperature alone is sufficient because animals with core body temperatures below 37°C are not hypersusceptible to fungal infections. Instead, we think that a combination of temperature resistance and other stress responsive pathways are important for pathogenesis. However, these pathways are also potentially linked to fungal adaptation to a changing climate. We are using an experimental evolution approach to identify stress pathways involved in fungal adaptation to extreme weather events and whether this increases infection potential.

We take a highly 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.


  1. Denham ST, Brammer B, Chung KY, Wambaugh MA, Bednarek JM, Guo L, CT Moreau, and Brown JCS. (2022). A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans. Cell Host & Microbe. PMCID: PMC9588642.
  2. Wambaugh MA, Denham ST, Ayala M, Brammer B, Stonhill MA, Brown JCS (2020). Synergistic and antagonistic drug interactions in the treatment of systemic fungal infections Elife 9: e54160. PMCID: PMC7200157.
  3. Denham ST, Wambaugh MA, and Brown JCS (2019). How environmental fungi cause a range of clinical outcomes in susceptible hosts. Journal of Molecular Biology 431(16): 2982-3009. PMCID: PMC6646061.
  4. Denham ST, Verma S, Reynolds RC, Worne CL, Daugherty JM, Lane TE, Brown JCS (2018). Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system. Infection and Immunity 86(3). PMCID: PMC5820953.
  5. Wambaugh MA*, Shakya VPS*, Lewis AJ, Mulvey MA, and Brown JCS (2017). High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance. PLoS Biology 15(6): e2001644. PMCID: PMC5478098. *These authors contributed equally to this work.
  6. Brown JCS, Nelson J, VanderSluis B, Deshpande R, Butts A, Kagan S, Polacheck I, Krysan DJ, Myers CL, and Madhani HD (2014). Unraveling the biology of a fungal meningitis pathogen using chemical genetics. Cell 159(5): 1168-87. PMCID: PMC4243055.
  7. Jarosz DF*, Brown JCS*, Walker GA, Datta MS, Ung WL, Lancaster AK, Rotem A, Chang A, Newby GA, Weitz DA, Bisson LF, Lindquist S (2014). Cross-kingdom chemical communication drives a heritable, mutually beneficial prion-based transformation of metabolism. Cell 158(5): 1083-93. PMCID: PMC4424051.*These authors contributed equally to this work.
  8. Jarosz DF*, Lancaster AK*, Brown JCS, and Lindquist S (2014). An evolutionarily conserved prion-like element converts wild fungi from metabolic specialists to generalists. Cell 158(5): 1072-82. PMCID: PMC4424049. *These authors contributed equally to this work.
  9. 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.
  10. Brown JC, Madhani HD (2012).  Approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling. PLoS Genet, 8(12), e1003168.
  11. Chun CD*, Brown JC*, Madhani HD (2011). A major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by Cryptococcus neoformans. Cell Host Microbe, 9(3), 243-51.
  12. Brown JC, Lindquist S (2009). A heritable switch in carbon source utilization driven by an unusual yeast prion. Genes Dev, 23(19), 2320-32.
Last Updated: 8/2/23