PROJECT SUMMARY
COVID-19 remains an ongoing global health crisis, in part due to emerging variants. Fundamental questions
remain about the mechanisms by which SARS-CoV-2 infection drives inflammation in the lower lung, in part
due to the lack of in vitro infection models. Better understanding of variant biology and the immune pathways
involved in early SARS-CoV-2 infection could offer insights for the development of novel therapeutic strategies.
The antiviral cytokines type I interferons and their downstream effects have been implicated in COVID-19.
SARS-CoV-2 may inhibit or promote interferon effects in some cell types in the lung, and this may differ
between viral variants. My preliminary work shows that organoids and lung slice cultures can be used to study
these early events in SARS-CoV-2 infection and identifies macrophages as a cell type that activates the
interferon pathway in infected cultures. Thus, I propose using quantitative PCR, single-cell RNA sequencing,
and flow cytometry to study viral variants and to deeply profile the changes to viral and host gene and protein
expression during infection. I will study highly relevant cell types that can interact with each other in a similar
fashion to the in vivo lung. I will study the interferon stimulated gene response and identify the cell types in
which it is being modulated or would be good targets for therapeutic intervention. This knowledge will be critical
to our efforts to combat the COVID-19 pandemic.
I am currently a fellow in Dr. Catherine Blish’s lab in the Division of Infectious Diseases at Stanford University
and I am in the process of being promoted to a full time Instructor position. Stanford University offers an
outstanding scientific environment, where all the resources necessary to the success of this project are made
available to me. My long-term goal is to become an independent physician-scientist, with a research focus in
respiratory viral pathogenesis. I aim to establish a research program focused on modeling established and
emerging infections in primary lung tissue with a goal of developing new treatments.
To achieve this goal, I have designed a tailored career development plan that comprises both formal and
informal training. This training will enhance my expertise in lung biology, immunology, and sequencing
analysis. Informal training in these topics will be provided by my mentor, Dr. Catherine Blish, and by the rest of
my advisory committee, Dr. Calvin Kuo, Dr. Mark Krasnow, Dr. Susan Holmes, and Dr. Ben Pinsky. With their
guidance, I will complete the proposed project, submit research manuscripts, obtain further funding, and obtain
an independent research position.