Molecular Mycology and Immunity Unit
Eric Van Dang, Ph.D. (He/Him/His)
Major Areas of Research
- Innate immune detection of fungal pathogens
- Fungal crosstalk with mammalian hosts
- Mechanisms of fungal persistence/colonization at barrier tissues
- Cellular mechanisms of antifungal immune response in vivo
The Molecular Mycology and Immunity Section (MMIS) studies the molecular and cellular interactions between fungi and their hosts. Mammalian barrier tissues (gut, skin, lungs) are colonized by a plethora of microbial species that play important roles in shaping host immunity and physiology. While most research has thus far focused on bacteria, fungi are increasingly recognized as important components of our commensal flora. In addition to commensals, there are a number of fungal pathogens that cause a high human disease burden, leading to 300 million infections and up to 1.5 million deaths per year globally. These infections are difficult to treat, due to a lack of effective drugs and the increased emergence of drug-resistant pathogens.
Our laboratory operates at the intersection of microbiology and immunology to understand the factors that dictate the outcome of fungal exposure at barrier tissues. We take an interdisciplinary approach leveraging fungal/mouse genetics, molecular biology, biochemistry, CRISPR, cellular immunology, and imaging approaches to address three major research topics:
- Mechanisms and impact of host colonization by fungi: A major interest in our group is understanding how fungi colonize and impact host barrier tissues. We utilize yeast forward genetic screens to identify molecules that drive fungal evasion of the host immune system. We also aim to identify fungal secondary metabolites that act on host receptors/signaling pathways in order to understand how fungal colonization impacts mammalian tissue physiology.
- Mechanisms and regulation of innate immune detection of fungi: Mammalian immune systems utilize germline-encoded pattern recognition receptors (PRRs) to
- detect invading microbes. Specific detection of fungal pathogens is largely mediated by extracellular sugar-sensing receptors of the C-type lectin receptor (CLR) family. While there has been major progress in identifying the ligands and downstream signaling pathways of these receptors, there is still much to learn about how CLR activation is regulated. We seek to understand the molecular pathways that activate/inhibit CLR signaling, and how these pathways are controlled by environmental cues sensed by myeloid cells in tissues. We are also focused on understanding mechanisms of cell-autonomous innate immunity to fungal pathogens, such as how intracellular fungi are detected and cleared by cytosolic surveillance pathways.
- Myeloid cell responses to fungal infection in vivo: We seek to understand the cellular mechanisms underlying protective versus aberrant immunity to fungal infection. One major interest is understanding how alternatively activated macrophages induced by type 2 cytokine signaling influence fungal immunity and infection outcomes. We are also interested in how dendritic cells interact with fungi to shape discrete T cell differentiation states. Lastly, we seek to dissect the roles of other recruited myeloid cells (monocytes, eosinophils, neutrophils, basophils) during fungal infection.
Ph.D., 2018, University of California, San Francisco
B.A., 2010, Johns Hopkins University
Dr. Dang received his undergraduate degree in Public Health Studies from Johns Hopkins University in 2010, where he studied T cell differentiation in the lab of Dr. Drew Pardoll. After college, he spent a year in London working in Dr. Anne O’Garra’s lab at the National Institute for Medical Research in Mill Hill. After a brief stint in medical school, he performed his graduate thesis work at the University of California, San Francisco in the laboratory of Dr. Jason Cyster. There he studied the role of oxysterols and cholesterol metabolism in regulating macrophage inflammatory responses. After receiving his Ph.D. in 2018, Dr. Dang joined the laboratory of Dr. Hiten Madhani at UCSF for his postdoctoral work. There he used forward genetic approaches to study mechanisms of immune system manipulation by the fungal pathogen Cryptococcus neoformans. Dr. Dang was hired as a tenure-track investigator in the NIAID Laboratory of Host Immunity and Microbiome in 2022. His group focuses on understanding the crosstalk between fungal pathogens/commensals and mammalian hosts.
Dang E.V., Lei S, Radkov A, Volk R.F., Zaro B.W., Madhani H.D. Secreted fungal virulence effector triggers allergic inflammation via TLR4. Nature. 2022 (In Press).
Dang EV, McDonald JG, Russell DW, Cyster JG. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation. Cell. 2017 Nov 16;171(5):1057-1071.e11.
Lu E, Dang EV, McDonald JG, Cyster JG. Distinct oxysterol requirements for positioning naïve and activated dendritic cells in the spleen. Sci Immunol. 2017 Apr 7;2(10):eaal5237.
Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG. Inflammation. 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science. 2014 Aug 8;345(6197):679-84.
Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011 Sep 2;146(5):772-84.