David R. Goodlett

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Academic Career Length

27Years (2000-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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7 August 2019 in Mass Spectrometry Reviews

Journal Article

Proteome analysis of tissues by mass spectrometry

4 March 2021 in Science Immunology

Journal Article

Deep-sea microbes as tools to refine the rules of innate immune pattern recognition

Anna E. Gauthier

Courtney E. Chandler

Valentina Poli

Francesca M. Gardner

Aranteiti Tekiau

Jonathan C. Kagan

The assumption of near-universal bacterial detection by pattern recognition receptors is a foundation of immunology. The limits of this pattern recognition concept, however, remain undefined. As a test of this hypothesis, we determined whether mammalian cells can recognize bacteria that they have never had the natural opportunity to encounter. These bacteria were cultivated from the deep Pacific Ocean, where the genus Moritella was identified as a common constituent of the culturable microbiota. Most deep-sea bacteria contained cell wall lipopolysaccharide (LPS) structures that were expected to be immunostimulatory, and some deep-sea bacteria activated inflammatory responses from mammalian LPS receptors. However, LPS receptors were unable to detect 80% of deep-sea bacteria examined, with LPS acyl chain length being identified as a potential determinant of immunosilence. The inability of immune receptors to detect most bacteria from a different ecosystem suggests that pattern recognition strategies may be defined locally, not globally.

16 May 2022 in Analytical Chemistry

Journal Article

Lipid A Structural Determination from a Single Colony

Hyojik Yang

Richard D. Smith

Courtney E. Chandler

J. Kristie Johnson

Shelley N. Jackson

Robert Ernst

31 August 2020 in Proceedings of the National Academy of Sciences

Journal Article

Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion inYersinia pestis

Courtney E. Chandler

Erin M. Harberts

Mark R. Pelletier

Iyarit Thaipisuttikul

Jace W. Jones

Robert Ernst

Significance: Immune evasion is a hallmark ofYersinia pestispathogenesis, including loss of pathogen-associated patterns recognized by Toll-like receptors. During its life cycle,Y. pestisalternates between mammalian hosts and arthropod transmission vectors and concurrently remodels its membrane, specifically modifying the structure of the lipid A portion of its lipopolysaccharide recognized by TLR4-MD2. Genomic analysis identified a single-nucleotide polymorphism that results in a premature stop in translation of the lipid A acyltransferasepagP, resulting in synthesis of a stealthy, hypoacylated lipid A structure absent in other Yersiniaceae. This provides evidence of lipid A as a crucial determinant inY. pestisinfectivity, pathogenesis, and host innate immune evasion and represents one of the earliest identified adaptations ofY. pestisfromYersinia pseudotuberculosis.

31 May 2022 in Cell Reports

Journal Article

Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids

Justin J. Zik

Sung Hwan Yoon

Ziqiang Guan

Gabriele Stankeviciute Skidmore

Ridhi R. Gudoor

Kathleen R. Ryan

Lipid A, the membrane-anchored portion of lipopolysaccharide (LPS), is an essential component of the outer membrane (OM) of nearly all Gram-negative bacteria. Here we identify regulatory and structural factors that together render lipid A nonessential in Caulobacter crescentus. Mutations in the ferric uptake regulator fur allow Caulobacter to survive in the absence of either LpxC, which catalyzes an early step of lipid A synthesis, or CtpA, a tyrosine phosphatase homolog we find is needed for wild-type lipid A structure and abundance. Alterations in Fur-regulated processes, rather than iron status per se, underlie the ability to survive when lipid A synthesis is blocked. Fitness of lipid A-deficient Caulobacter requires an anionic sphingolipid, ceramide phosphoglycerate (CPG), which also mediates sensitivity to the antibiotic colistin. Our results demonstrate that, in an altered regulatory landscape, anionic sphingolipids can support the integrity of a lipid A-deficient OM.

24 March 2023 in Cancer Immunology Research

Journal Article

The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides

Javier Antonio Alfaro

+18

Tumor antigens can emerge through multiple mechanisms, including translation of noncoding genomic regions. This noncanonical category of tumor antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry (MS) to enable the discovery of noncanonical MHC class I–associated peptides (ncMAP) from noncoding regions. Considering that the emergence of tumor antigens can also involve posttranslational modifications (PTM), we included an open search component in our pipeline. Leveraging the wealth of MS-based immunopeptidomics, we analyzed data from 26 MHC class I immunopeptidomic studies across 11 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant PTMs, using spectral matching and controlled their FDR to 1%. The noncanonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 55%. The data reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive therapeutic targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targets for T-cell therapies or vaccine development.

About Me

David R Goodlett is currently a Professor of Biochemistry and Microbiology at the University of Victoria, where he is also Director of the Genome BC Proteome Centre. He is a mentor for the Chemical Biology group at the University of Gdanskâ€™s International Centre for Cancer Vaccine Science. Previously, he was a Professor at the University of Maryland in Baltimore, MD (2013-2020). From 2012–2016, he was a Finland Distinguished Professor (FiDiPro) at the University of Turku in Finland. The research at the University of Turku was focused on the discovery of serum protein markers that predict children who will develop type 1 diabetes before the appearance of autoantibodies as well as cardiovascular disease in young Finns. From 2013 to 2016, he worked as the Isaac E. Emerson Professor of Pharmaceutical Sciences at the University of Maryland School of Pharmacy and from 2013–2015, he was the Director of the UMB School of Pharmacy MS Center. From 2004–2012, he was a Professor of Medicinal Chemistry at the University of Washington in Seattle, WA, and the Director of the School of the pharmacy mass spectrometry facility. He received his B.S. and M.S. degrees in Chemistry from Auburn University in 1982 and 1988, and his Ph.D. in Biochemistry from North Carolina State University in 1991. His research includes hypothesis-generating, discovery-based efforts in protein and lipid A structure-function relationships in infectious organisms, proteomics technology development and informatics.

David R. Goodlett

David R. Goodlett

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