Joseph M. Luna, PhD

Assistant Professor
Department of Biochemistry
School of Medicine
Member
Center for RNA Science and Therapeutics
School of Medicine

Research Information

Research Interests

Positive sense RNA virus genomes face a unique challenge in that a single RNA is capable of launching infection along with a multi-faceted innate immune response. A central focus of the Luna lab is to shed light on the dynamic processes by which RNA virus genomes interact with a constellation of translation factors and RNA binding proteins (RBPs) whose collective activity determines infection trajectories in a cell. We use reverse genetic strategies of hepaci-, flavi- and corona- RNA virus families as model systems to probe cellular responses to infectious RNA. By combining these tools with CRISPR based functional genomics, various transcriptome profiling strategies, and advanced imaging methods, we aim to determine the order of events by which specific RBPs regulate viral genomes and innate immune responses. A more thorough, systems level understanding of these processes will help illuminate how viruses and cells navigate the stress of infection. These insights will inform disease states linked to altered innate immune and RBP activities, such as certain neurodegenerative diseases and cancers.

In addition, we are committed to training and mentoring the next generation of scientists in biomedical research, particularly from under-represented groups. We further prioritize scientific outreach efforts at all levels to educate, inform and inspire.

Research Projects

The Luna lab explores the interface between molecular virology and the systems-level host response to viral infections, with a special emphasis on RNA driven processes. Incorporating classic virology approaches with innovative sequencing and imaging methods, our approach emphasizes the investigation of host-pathogen interactions in a diverse array of disease-relevant contexts, from COVID-19 to cancer. 

Current research projects include:
1. RNA dynamics during infection and stress. A common cellular feature of RNA virus infection is an abrupt host- or virus- driven halt in translation that results in stress granules (SGs)–transient accumulations of mRNA, initiation factors, and RNA-binding proteins (RBPs) that phase separate from surrounding cytoplasm. Current efforts aim to dissect role(s) for dynamic SG signaling during RNA virus infection, with broader links to RNA metabolism. 

2. Repurposing RNA driven innate immune responses. How cells define self versus non-self RNA is often dysfunctional in many disease states. As this homeostatic process can powerfully affect pathogenic outcomes, it may provide a new therapeutic foundation for a wide range of diseases. We aim to harness RNA driven innate immune responses for therapeutic applications in cancer and other diseases using rationally designed RNA based ligands. 

3. RNA virus reverse genetics. Based on recent work to establish a non-infectious reverse genetics system for SARS-CoV-2, we aim to explore specific RBP focused questions in the context of viral RNA replication in cells. These studies include the role(s) of viral RBPs in modulating host immune responses and the roles of host RBPs in sensing CoV induced translation shutoffs. We are also interested in extending reverse genetics strategies for additional viruses that impact human health. 

Publications

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Education

PhD
The Rockefeller University
2015
Post Doc
The Rockefeller University