涩里番

Speaker

Henry L. Hillman Professor of Molecular Biology, Princeton University

The Cristea laboratory investigates host–pathogen interactions and mechanisms of cellular defense during infection with human viruses. Towards this goal, Cristea has promoted the integration of virology with proteomics, bridging developments in mass spectrometry to discoveries in virology. Her laboratory has contributed to the emergence of the research field of nuclear viral DNA sensing in immune response, to uncovering functional organelle remodeling events during infections, to discovering antiviral factors for therapeutic intervention, and to characterizing a virus microenvironment. Cristea is the editor-in-chief of Molecular & Cellular Proteomics, a past president of US HUPO, a past chair of B/D-HPP of HUPO, and chair of the infectious disease team of HUPO B/D-HPP. She has taught the summer proteomics course at CSHL for over ten years. She was recognized with several awards, including the NIDA Avant-Garde Award (DP1), Mallinckrodt Scholar Award, Discovery Award in Proteomics from HUPO, Paul Allen Distinguished Investigator Award, and the George Khoury NIH Director’s WALS lectureship.

The ASBMB Breakthroughs webinar series offers a window into the cutting-edge biochemistry and molecular biology research driving discovery.

Viral infections spread within complex and dynamic cellular microenvironments that shape the outcome of infection. As such, intra-cellular communication cascades, as well as communication between infected cells and cells in the surrounding tissue, create a virus microenvironment. Here, we will describe some of our efforts to characterize communication events at the intra- and inter-cellular levels. At the intra-cellular level, we will consider organelle remodeling and alterations in organelle–organelle contacts that modulate cellular metabolism and immune responses during infections with several DNA and RNA viruses. We integrate super-resolution microscopy, cryotomography, proteomics and molecular assays to monitor mitochondrial remodeling and its effect on mitophagy and mitochondrial bioenergetics. At the interface between metabolic rewiring and immune signaling, we consider that several prevalent human viruses, including human cytomegalovirus (HCMV), induce a Warburg-like effect that results in increased lactate production. We discover virus-induced lactylation of intrinsically disordered regions of host immune factors that suppresses their functions and facilitates virus spread during infections with HCMV and herpes simplex virus 1 (HSV-1). Further investigating communication at the inter-cellular level, we establish an approach to characterize a virus microenvironment, distinguishing cell populations based on their proximity to an infection site. We show that a viral infection can prime uninfected, proximal cells for infections with several viruses. Overall, these findings demonstrate how infection reshapes the surrounding microenvironment through intra- and inter-cellular signaling to facilitate viral spread and how spatial proximity to an infection guides cell fate.