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Dr. David Gonzalez
Mass Spectrometry Based Drug Discovery
David Gonzalez, Ph.D.
Skaggs School of Pharmacy and Pharmaceutical Sciences
Department of Pharmacology, School of Medicine
Research Summary: Antivirulence Strategies
The Gonzalez laboratory aims to study the chemical biology that governs the host-pathogen interaction. In particular, we will focus on combating antibiotic resistant bacterial pathogens commonly referred to as super bugs. We aim to identify and characterize key virulence factors and important host immune responses in order to develop strategies for pharmacological development. Discovery of novel sustainable therapeutic agents have not kept pace with the threat that bacterial pathogens pose to mankind. One contributing factor to this innovation gap is the lack of information describing system‐wide bacterial and host chemical responses to environmental perturbations. A better understanding of mechanisms that regulate the balance and communication between host and pathogen cells can lead to the discovery of previously unrecognized therapeutic targets. Our approach will incorporate new technologies in the field of high-end mass spectrometry to accurately detect and quantify proteomic and metabolomic dynamics that occur during the interaction between a bacterial pathogen and different environmental challenges (e.g. host immune cells or competing bacteria). Factors identified during these interactions will be characterized in both unbiased high‐throughput and targeted, hypothesis‐driven fashions, and when the opportunity arises, translational studies of therapeutic value will be undertaken in tissue culture and murine infection models.
B.A. in Chemistry (2006) California State University, San Marcos; Ph.D. (2011) University of California, San Diego; Postdoctoral Fellow in Molecular Pathogenesis (2011-2014) University of California, San Diego.
Awards and Honors:
UC President’s Postdoctoral Award (2014), IRACDA UCSD Fellowship (2013), A.P. Giannini Medical Fellow (2011), AGEP Fellow (2006), Competitive-edge Predoctoral Award (2006), UCSD STARS Program (2005).
Yale Bouchet Honor Society Inductee for excellent research and commitment to diversity and equality (2010).
Key Contributions to Pharmaceutical Sciences
- Development of mass spectrometry tools to study specialized molecules of bacterial pathogenesis.
- Elucidated mechanisms used by multidrug resistant Staphylococcus aureus to clear host microbiome.
Selected Recent Publications (from 20 peer-reviewed articles)
- Lee et al. (2008). Discovery of a widely distributed toxin biosynthetic gene cluster. Proc Natl Acad Sci USA. 105:5879-84.
- Gonzalez et al. (2010). Clostridiolysin S: A post-translationally modified biotoxin from Clostridium botulinum. J Biol Chem. 285:27798-805.
- Gonzalez et al. (2012). Novel phenol soluble modulin derivatives in community-associated methicillin-resistant Staphylococcus aureus identified through imaging mass spectrometry. J Biol Chem 287:13889-98.
- Kersten et al (2013). Glycogenomics as a mass spectrometry guided genome mining method for microbial glycosylated molecules. Proc Natl Acad Sci USA 110:E4407-16.
- Yamanaka K et al (2014). Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proc Natl Acad Sci USA 111:1957-62.
- Gonzalez et al. (2014) N-Terminal ArgD Peptides from the Classical Staphylococcus aureus Agr System Have Cytotoxic and Proinflammatory Activities. Chem Biol 21:1457-62.
Potential Collaborative Programs with the Pharmaceutical Industry
Multiplexed quantitative proteomics, metabolomics, and posttranslational modification characterization.
Targeting virulence mechanisms as therapeutic targets in leading bacterial pathogens.