Anita Sil, MD, PhD

Howard Hughes Medical Institute Early Career Investigator
Professor
Department of Microbiology and Immunology
+1 415 502-4810
Research Overview: 

We study the fungal pathogen Histoplasma capsulatum, which is a soil organism that can infect and colonize cells of the innate immune system after inhalation into mammals. Temperature is a major signal that triggers a developmental switch between the soil and host forms of the fungus.  Our research is driven by two key questions. First, how do cells sense temperature and make a developmental switch from the soil to the host program? We focus on temperature because it is a sufficient signal to recapitulate the morphologic switch between Histoplasma filaments (the soil form) and yeast (the host form) in culture. This question is critical to understanding the basic biology of Histoplasma as well as a number of closely related fungi such as Blastomyces ,Coccidioides , and Paracoccidioides , each of which is a ubiquitous pathogen of immunocompetent hosts in endemic areas. In fact, one of the fascinating evolutionary questions about these environmental fungi is how regulatory circuits have evolved to link morphology and virulence programs with growth at host is be an entry point to broader studies of host-fungal interactions, since it will define critical developmental changes that promote the expression of virulence traits, as well as delineate molecular landmarks that will allow us to stage the interactions of the fungus with host cells.

Second, how does H. capsulatum defy the innate immune response to take up residence, often permanent, in immunocompetent hosts? The past ten years have witnessed an exponential increase in our understanding of the innate immune response to microbes, and yet, in the case of fungi, our insight is rudimentary at best. Our studies explore the molecular communication at the host-pathogen interface between H. capsulatum and the macrophage. H. capsulatum displays extremely robust macrophage colonization, so it is currently the best fungal candidate to probe the Achilles' heel of these powerful innate immune cells and determine novel mechanisms of virulence that have evolved in eukaryotic pathogens.

Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Immunology
Research Summary: 
Regulation of cell shape and virulence by temperature in the fungal pathogen Histoplasma capsulatum
Mentorship Development: 

11/23/20   Building Community in the UCSF MSTP

Websites

Publications: 

Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.

Cell

Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano KA, Hayashi JM, Carlson-Stevermer J, Zengel JR, Richards CM, Fozouni P, Oki J, Rodriguez L, Joehnk B, Walcott K, Holden K, Sil A, Carette JE, Krogan NJ, Ott M, Puschnik AS

Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy.

Cell

Fozouni P, Son S, Díaz de León Derby M, Knott GJ, Gray CN, D'Ambrosio MV, Zhao C, Switz NA, Kumar GR, Stephens SI, Boehm D, Tsou CL, Shu J, Bhuiya A, Armstrong M, Harris AR, Chen PY, Osterloh JM, Meyer-Franke A, Joehnk B, Walcott K, Sil A, Langelier C, Pollard KS, Crawford ED, Puschnik AS, Phelps M, Kistler A, DeRisi JL, Doudna JA, Fletcher DA, Ott M

Recurrent Loss of abaA, a Master Regulator of Asexual Development in Filamentous Fungi, Correlates with Changes in Genomic and Morphological Traits.

Genome biology and evolution

Mead ME, Borowsky AT, Joehnk B, Steenwyk JL, Shen XX, Sil A, Rokas A

Molecular regulation of Histoplasma dimorphism.

Current opinion in microbiology

Sil A