New Anti-Infective Therapies
Skaggs School of Pharmacy and Pharmaceutical Sciences
Professor, Division Chief and Vice Chair
Department of Pediatrics, School of Medicine
Dr. Nizet’s laboratory interests lie in understanding the fundamental mechanisms of bacterial pathogenesis and the innate immune system, with a special focus on invasive and antibiotic-resistant pathogens. Using a variety of molecular genetic approaches, the laboratory discovers and characterizes bacterial virulence factors involved in cytotoxicity, adherence, invasion, inflammation, molecular mimicry and resistance to immunologic clearance. In companion studies, we investigate the contribution of host factors such as antimicrobial peptides, leukocyte surface receptors, signal transduction pathways, and transcription factors in defense against invasive bacterial infection.
We have shown that the basic information gained through this platform can lead to novel treatment strategies for infectious diseases, involving targeted neutralization of bacterial virulence phenotypes and pharmacologic boosting of host innate immune cell function and drug repurposing. Additional studies examine innovative nano therapeutic and vaccine approaches to prevent infection by leading pathogens.
Education: B.A. in Biology (1984) Reed College; M.D. (1989) Stanford University, Pediatric Residency & Chief Residency (1993) Harvard University, Pediatric Infectious Diseases Fellowship (1997) University of Washington.
Awards and Honors: American Lung Associate Career Investigator Award (2004); American Heart Association Established Investigator Award (2004); American Society for Clinical Investigation (2006); E. Mead Johnson Award for Research in Pediatrics (2008); American Asthma Foundation Senior Investigator Award (2008); Fellow, American Academy of Microbiology (2012). UCSD Chancellor’s Award for Excellence in Postdoctoral Fellow Mentoring (2013), UCSD Chancellor's Associates Award for Excellence in Research in Science and Engineering (2017). UCSD Health Sciences Award for Excellence in Faculty Mentoring (2018).
Leadership Experience: Track Leader, Microbiology & Immunology, UCSD Biomedical Sciences Graduate Program (2005); Chief, Division of Host-Microbe Systems & Therapeutics UCSD (2007-). Vice Chair for Basic Research, Department of Pediatrics (2015-); Director, UCSD Collaborative to Halt Antibiotic-Resistant Microbes (CHARM, 2017 -).
- Pathogens and Host Defense (BIOM 253)
- From the Molecule to the Organism (BIOM 200)
- Discovered the genetic basis and mechanism of action of numerous virulence factors produced by the leading human bacterial pathogens, identifying new targets for therapy.
- Elucidated many key functions of the mammalian innate immune system, highlighting strategies for boosting phagocytic cell defenses against drug-resistant pathogens.
- Studied how existing pharmaceutical agents, including both antibiotics and other drug classes, can synergize with the innate immune system and thus may be repurposed to aid in infectious disease therapy.
van Sorge NM, et al. (2014). The classical Lancefield antigen of group A Streptococcus is a virulence determinant with implications for vaccine design. Cell Host Microbe 15:729-740
Corriden R, Hollands A, Olson J, Derieux J, Lopez JM, Gonzalez DJ, Nizet V. (2015) Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat Comm 6:8369.
LaRock CN, et al (2016) IL-1β is an innate immune sensor of microbialproteolysis. Sci munol 1:eaah3539.
Valderrama JA, et al (2017) Group A streptococcal M protein activates the NLRP3 inflammasome. Nat Microbiol 2:1425–1434.
Selected Recent Publications (from >410 peer-reviewed articles)
- 20 years’ experience in clinical infectious diseases and fundamental microbiology, immunology and anti-infective pharmacology research.
- Broad array laboratory approaches to understanding host-pathogen interactions and develop innovative and therapeutic approaches against antibiotic-resistant pathogens
- Numerous active laboratory collaborations with biotechnology and pharmaceutical company partners advancing therapeutic concepts.