Assistant Professor of Pathology
B.A. Pomona College
Ph.D. Massachusetts Institute of Technology
Jessica Brown's Lab Page
Jessica Brown's PubMed Literature Search
Molecular Biology Program
Pathogenesis, fungal genetics, host-pathogen interaction
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.
I 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. I am 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 more targeted, less toxic anti-fungal drugs.
Some of my initial research questions will include:
- 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?
- 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?
My lab takes 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.
- Jarosz DF*, Brown JC*, Walker GA, Datta MS, Ung LW, Lancaster AK, Chang A, Weitz DA, Bisson LF, Lindquist S (2014). Cross-kingdom chemical communication drives a mutually beneficial prion-based transformation of metabolism. Cell (in press).
- Jarosz DF*, Lancaster AK*, Brown JC, Lindquist S (2014). An evolutionarily conserved epigenetic element converts wild fungi from metabolic specialists to generalists. Cell (in press).
- Brown JC, Nelson J, VanderSluis B, Deshpande R, Butts A, Kagan S, Polacheck I, Krysan DJ, Myers CL, Madhani HD. Unraveling the biology of a fungal meningitis pathogen using chemical genetics. Cell. 2014 Nov 20;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). 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). A heritable switch in carbon source utilization driven by an unusual yeast prion. Genes Dev, 23(19), 2320-32.