Development of an improved live-attenuated influenza vaccine
Our goal is to develop a new and more effective live-attenuated influenza vaccine (LAIV) by understanding the mechanism(s) underlying the current LAIV’s temperature sensitive (ts) phenotype and using that knowledge to improve LAIV. We hypothesize that a new, more effective LAIV can be developed by selecting an optimal combination of mutations that (i) confer even greater temperature sensitivity, resulting in viral replication only in the lower temperatures of the nasal cavity and extreme upper airway and (ii) selectively favor viral transcription over genome replication – resulting in abundant protein expression (and immunogenicity) but minimal production of infectious progeny virus. Our ultimate objective is to contribute to the development of a new universal influenza vaccine that leverages LAIV’s superior ability to elicit T cell responses and to protect against infection by mismatched influenza viruses.
Collaborative development of novel therapies for HIV infection
We are collaborating with Ben Miller and Clara Kielkopf, to develop and test new first-in-class therapies that apply emerging concepts in RNA biology to the treatment of HIV infection, including strategies to effect a functional cure in persons living with HIV. Thus, we are exploring novel approaches that target either RNA structures involved in HIV-1 replication (Dr. Miller) or host proteins involved in viral transcription and reactivation from latency (Dr. Kielkopf), using cell culture models for viral replication.