Identifying Mitophagy Receptors as Targets in
PI: Michael Ragusa, PhD
Assistant Professor of Chemistry
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and challenging cancers to treat in the United States. The growth of PDAC tumors is dependent on a cellular degradation process, termed autophagy. We are combining biochemical and cellular approaches to uncover the role of autophagy in PDAC.
Understanding Early-life Influenza Antibody Repertoire Imprinting Through Infection or Vaccination
PI: Jiwon Lee, PhD
Ralph and Marjorie Crump Assistant Professor of Engineering
Influenza is a rapidly evolving virus that poses persistent global health threat. Due to the ubiquitous nature of influenza, almost all children are exposed to influenza virus by the age of 6. From this early exposure to influenza via infection or vaccination, the first influenza antibody repertoire is established, and it is reshaped continuously through repeated exposures to a multitude of different influenza virus strains during one’s lifetime. Recent studies based on epidemiology, modeling, and traditional serology metrics have suggested that the initial antibody repertoire generated from the first exposure is ‘imprinted’ in the immune system. The constraints imposed by the imprinted antibody repertoire exert a major influence on the nature of the antibody response elicited upon subsequent challenges, potentially impeding the effectiveness of novel vaccines. For this project, we will track the longitudinal continuity of anti-influenza antibody repertoires as a function of initial exposure route and test the hypothesis that the first exposure through infection results in stronger imprinting of initial influenza antibody repertoire than the first exposure through vaccination.
Electrogenic Modulation of Signal Decoding in Presynaptic Terminals
PI: Michael Hoppa, DPhil
Assistant Professor of Biological Sciences
The generation and transmission of electrical signals is fundamental to initiating the release of neurotransmitters in the nervous system. This proposal will take advantage of a number of novel optical approaches to determine the molecular mechanisms that regulate electrical signalling in nerve terminals and define their impact on neurotransmission. Compromised neurotransmission is a known or suspected defect in several neurological diseases, thus a better understanding electrical signaling in nerve terminals could suggest new therapeutic approaches.
Impact of Pre-existing T Cell Memory on Oncolytic Virus Therapy
PI: Pamela Rosato, PhD
Assistant Professor of Microbiology and Immunology
Oncolytic viruses (OV) are a promising class of cancer therapeutics that work by preferentially infecting and killing tumor cells. Many OVs are viruses to which individuals have pre-existing T cell immunity, through vaccination or natural infection (e.g. HSV-1, measles, and vaccinia virus), yet the impact of this immunity on therapeutic efficacy and patient outcome is unclear. Recent findings have revealed that virus-specific memory T cells populate tumors, often to high frequency. Because of their location within the tumor, it is likely these memory T cells will encounter viral antigen during OV therapy. In light of this, we are interested in understanding the impact of oncolytic virus-specific T cells on OV therapy to then be able to refine and redesign oncolytic viruses for improved efficacy.