Victor DeFilippis is an associate professor at the Vaccine and Gene Therapy Institute. After receiving his bachelor's degree from the University of Montana he received a Master's degree in Biology from Wayne State University. He completed his Ph.D. examining virus evolution at the University of California, Irvine. He conducted his postdoctoral work at the Vaccine and Gene Therapy Institute of OHSU.

Research in Dr. DeFilippis’ laboratory focuses on the molecular biology of innate immune signaling and its multiple links with adaptive immune responses such as the generation of antibody and T cell responses. This includes investigating mechanistic questions that yield insight into the basic biology of related phenomena as well as translational projects that apply these principles to problems such as identifying novel antiviral therapies, enhancing vaccine potency, and potentiating cancer immunotherapies. The primary area of research involves the cGAS-STING innate signaling pathway. This is an evolutionarily conserved intracellular apparatus that reacts to the atypical presence of cytosolic DNA. The detection of DNA in the cytosol leads to an array of inducible responses that include secretion of cytokines (especially type I interferons), apoptosis, and autophagy. Ultimately these processes lead to establishment of inflammatory tissue states that both block microbial growth and drive adaptive immune responses. As such, its dysfunction can lead to serious disease but it can also be harnessed pharmacologically to devise novel tools and clinical interventions for a wide array of conditions.     

The laboratory employs many techniques of cellular and molecular biology including forward and reverse genetics approaches (ectopic expression methods, CRISPR/Cas genome editing) as well as larger scale methods such as functional genomics, transcriptomics, and high throughput chemical screens. Many transgenic mouse and nonhuman primate models are also employed in the context of vaccine function and cancer.

Specific foci of inquiry include the following:

1) Discovery and characterization of novel compounds that stimulate cGAS-STING induction

The host innate immune response can be highly effective in both preventing replication of phylogenetically diverse viral pathogens but also in enhancing the initiation and establishment of adaptive immune responses. This is particularly true of the response induced by cGAS-STING activation. In light of this we employ high throughput screening strategies to identify new small molecules capable of triggering cGAS-STING associated phenotypes. We then dissect their mechanisms of action using molecular biological methods and characterize their in vivo utility as vaccine adjuvants and ability to enhance cancer therapies.

2) Development of novel vaccines against emerging viruses

Mosquito transmitted viruses such as Chikungunya and Zika represent globally impactful infections that can arise with remarkable swiftness. As such, adaptable vaccine platforms are needed to address the inevitability and unknown nature of their emergence. To address this the laboratory utilizes in vitro synthesized virus like particles as a replication incompetent viral mimic and pairs this with novel adjuvant combinations to identify safe and efficacious ways to elicit protective immunity. These platforms also represent powerful tools to investigate the mechanistic bases of vaccine function.