David Gonzalez, Ph.D.
Associate Professor of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences
The last 100 years of microbiology research have clearly established that symbiotic and pathogenic microbes colonizing humans have the ability to impact health, disease, and drug action. A next step in studying the complex interaction between host and microbe is to "directly" define the molecular factors that govern biological function (i.e. proteins, metabolites, posttranslational modifications) and delineate their associated mechanisms of action. Towards this goal, the Gonzalez laboratory utilizes a systems scale to single target approach to study bacterial pathogenesis, host responses to infection, and the human microbiome. At its core, the laboratory develops and applies multiplexing quantitative proteomics tools to simultaneously track thousands of protein dynamics and associated post-translational modifications in an accurate and high throughput fashion. We then interface microbiology techniques to characterize important factors identified during these interactions. When appropriate, translational studies of therapeutic value are undertaken in tissue culture, murine models, and by the analysis of human biospecimens. This information is then used to design novel strategies for the detection or treatment of microbial-driven infectious diseases in humans.
Markmiller S, Soltanieh S, Server KL, Mak R, Jin W, Fang MY, Luo EC, Krach F, Yang D, Sen A, Fulzele A, Wozniak JM, Gonzalez DJ, Kankel MW, Gao FB, Bennett EJ, Lécuyer E, Yeo GW. Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules. Cell. 2018 Jan 25;172(3):590-604.
Lapek JD Jr, Mills RH, Wozniak JM, Campeau A, Fang RH, Wei X, van de Groep K, Perez-Lopez A, van Sorge NM, Raffatellu M, Knight R, Zhang L, Gonzalez DJ. Defining Host Responses during Systemic Bacterial Infection through Construction of a Murine Organ Proteome Atlas. Cell Syst. 2018 May 23;6(5):579-592.
Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD Jr, Zhang L, Wang WB, Hao S, Flythe MD, Gonzalez DJ, Cani PD, Conejo-Garcia JR, Xiong N, Kennett MJ, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell. 2018 Oct 18;175(3):679-694.
Wierzbicki IH, Campeau A, Dehaini D, Wei X, Ying M, Sands JS, Lamsa A, Pogliano J, Fang RH, LaRock CN, Zhang L, Gonzalez DJ. Group A Streptococcal S protein utilizes red blood cells as immune camouflage and is a critical determinant for adaptive immunity evasion. Cell Reports. 2019 Dec 3;29(10):2979-2989.
Wozniak JM, Mills RH, Olson J, Caldera JR, Poore GD, Carrillo-Terrazas M, Tsai CM, Vargas F, Knight R, Dorrestein PC, Liu G, Nizet V, Sakoulas G, Rose W, Gonzalez DJ. Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Molecular Signatures. Cell. 2020 Sep 3;182(5):1311-1327.