Tamara L. Doering, M.D., Ph.D.

Professor
Molecular Microbiology

Molecular Microbiology and Microbial Pathogenesis Program
Molecular Cell Biology Program
Plant and Microbial Biosciences Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-747-5597

  • 314-362-2761

  • 314-362-1232

  • 10230 McDonnell Pediatric Research Building

  • doering@wustl.edu

  • doeringlab.com

  • biochemistry, biosynthetic pathways, cell biology, eukaryotic pathogen, gene regulation, genomic variants, glycobiology, host-pathogen interactions, microbial pathogenesis, pathogenic fungi, sterol transport, yeast

  • Biology and pathogenesis of the pathogenic fungus Cryptococcus neoformans

Research Abstract:

We aim to do rigorous science in a supportive and welcoming environment that prioritizes career development and opportunities for trainees. Our specific research interest is the fundamental biology and host interactions of the pathogenic fungus Cryptococcus neoformans. This yeast causes serious infections in immunocompromised individuals worldwide, killing almost 200,000 people each year, mainly in developing countries. Our goal is to elucidate unique aspects of cryptococcal biology that are of biological interest and may suggest targets for badly needed antifungal chemotherapy.

The main virulence factor of C. neoformans is its extensive polysaccharide capsule, a unique protective structure that is required for virulence and changes dramatically in response to environmental cues. The chemical structure of the cryptococcal capsule is known, but many questions remain about its synthesis, assembly, and regulation. The enzymes and pathways of capsule biosynthesis, and how we might inhibit them, are one major interest in the lab. In related studies, we are combining new technologies and approaches in computational biology with molecular experimentation to examine capsule regulation. We are also applying these methods to studies of naturally occurring genome variants that influence virulence and the mechanisms by which they do so.

Another area of focus is how this fungal pathogen interacts with host cells during infection, with the aim of understanding and potentially influencing these critical events. Image-based screening to explore this area has led us to study topics that range from host kinases and fungal mitochondria to lipid modification of proteins and sterol transport.

Overall, we use a range of approaches to study topics in cryptococcal biology that offer exciting and unique biology with potential for alleviating a severe disease. We hope our work will increase our basic science knowledge, deepen our understanding of fungal pathogenesis, and enhance the potential for development of new therapeutic agentss.

Selected Publications:

Recent publications from the Doering lab (* indicates graduate students):

Manning Y. Huang, Meenakshi B. Joshi, Michael J. Boucher, Sujin Lee, *Liza C. Loza, *Elizabeth A. Gaylord, Tamara L. Doering, Hiten D. Madhani (2022). Short homology-directed repair using optimized Cas9 in the pathogen Cryptococcus neoformans enables rapid gene deletion and tagging. Genetics, 220(1). doi: 10.1093/genetics/iyab180. [34791226]

*Julia C. V. Reuwsaat, Daniel P. Agustinho, *Heryk Motta, *Andrew L. Chang, Holly Brown, Marilene H. Vainstein, Livia Kmetzsch, Michael R. Brent, and Tamara L. Doering (2021). The transcription factor Pdr802 regulates Titan cell production and pathogenicity of Cryptococcus neoformans. mBio, 12 (2):e03457, doi: 10.1128/mBio.03457-20. [33688010]

*Liza Loza and Tamara L. Doering. Glycans of the pathogenic yeast Cryptococcus neoformans and related opportunities for therapeutic advances (2021). Chapter 1.20, pp 479-506, Comprehensive Glycoscience, 2nd Edition, ed. Joseph J. Barchi, Jr. Elsevier BV. ISBN 9780128222447

*Julia C. V. Reuwsaat, Tamara L. Doering, and Livia Kmetzsch (2021). Too much of a good thing: Overproduction of virulence factors impairs cryptococcal pathogenicity. Microbial Cell, 8 (5), 108-110, doi: 10.15698/mic2021.05.750. [33981763]

Tanya R. McKitrick, Margaret E. Ackerman, Robert Anthony, Clay S. Bennett, Michael Demitriou, Gregory A. Hudalla, Katharina Ribbeck, Stefan Ruhl, Christina M. Woo, Loretta Yang, Seth J. Zost, Ronald L. Schnaar, and Tamara L. Doering (2021). The Crossroads of Glycoscience, Infection, and Immunology. Frontiers in Microbiology. doi: 10.3389/fmicb.2021.731008 [34646251]

*Lucy X. Li, Camaron Hole, Matthew Williams, Javier Rangel-Moreno, Shabaana Khader, and Tamara L. Doering. Cryptococcus neoformans evades pulmonary immunity by modulating xylose precursor transport (2020). Infection and Immunity, https://doi.org/10.1128/IAI.00288-20. PMID: 32423915.

*R. Blake Billmyre, *Shelly A. Clancey, *Lucy X. Li, Tamara L. Doering, and Joseph Heitman (2020). Hypermutation in Cryptococcus reveals a novel pathway to 5-fluorocytosine (5FC) resistance. Nature Communications, 11(1), 127. [31913284] PMCID: PMC6949227.

*Elizabeth A. Gaylord, *Hau Lam Choy, and Tamara L. Doering (2020). Dangerous Liaisons: Interactions of Cryptococcus neoformans and host phagocytes. Pathogens, 9 (11), 891-905, doi: 10.3390/pathogens9110891. [33121050]

*Andrew L. Chang, *Yiming Kang, and Tamara L. Doering (2019). Cdk8 and Ssn801 regulate oxidative stress resistance and virulence in Cryptococcus neoformans resistance. mBio 10:e02818-18. https://doi.org/10.1128/mBio.02818-18.

Last Updated: 5/21/2022 2:40:53 PM

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