Our lab explores topics at the interface between molecular virology and the systems-level host response to RNA virus 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.
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.
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.
- Ricardo-Lax I*, Luna JM*, Thao TTN, Le Pen J, Yu Y, Hoffmann HH, Schneider WM, Razooky BS, Fernandez-Martinez J, Schmidt F, Weisblum Y, Trüeb BS, Berenguer Veiga I, Schmied K, Ebert N, Michailidis E, Peace A, Sánchez-Rivera FJ, Lowe SW, Rout MP, Hatziioannou T, Bieniasz PD, Poirier JT, MacDonald MR, Thiel V, Rice CM.
Replication and single-cycle delivery of SARS-CoV-2 replicons.
Science. 374(6571):1099-1106 (2021)
- Frank MO, Blachere NE, Parveen S, Hacisuleyman E, Fak J, Luna JM, Michailidis E, Wright S, Stark P, Campbell A, Foo A, Sakmar TP, Huffman V, Bergh M, Goldfarb A, Mansisidor A, Patriotis AL, Palmquist KH, Poulton N, Leicher R, Vargas CDM, Duba I, Hurley A, Colagreco J, Pagane N, Orange DE, Mora K, Rakeman JL, Fowler RC, Fernandes H, Lamendola-Essel MF, Didkovsky N, Silvera L, Masci J, Allen M, Rice CM, Darnell RB.
DRUL for school: Opening Pre-K with safe, simple, sensitive saliva testing for SARS-CoV-2.
PLoS One. 16(6):e0252949 (2021)
- Rozen-Gagnon K, Gu M, Luna JM, Luo JD, Yi S, Novack S, Jacobson E, Wang W, Paul MR, Scheel TKH, Carroll T, Rice CM.
Argonaute-CLIP delineates versatile, functional RNAi networks in Aedes aegypti, a major vector of human viruses.
Cell Host Microbe. 29(5):834-848.e13 (2021)
- Hoffmann HH*, Sánchez-Rivera FJ*, Schneider WM*, Luna JM*, Soto-Feliciano YM, Ashbrook AW, Le Pen J, Leal AA, Ricardo-Lax I, Michailidis E, Hao Y, Stenzel AF, Peace A, Zuber J, Allis CD, Lowe SW, MacDonald MR, Poirier JT, Rice CM.
Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.
Cell Host Microbe. 29(2):267-280.e5 (2021)
- Schneider WM*, Luna JM*, Hoffmann HH*, Sánchez-Rivera FJ*, Leal AA, Ashbrook AW, Le Pen J, Ricardo-Lax I, Michailidis E, Peace A, Stenzel AF, Lowe SW, MacDonald MR, Rice CM, Poirier JT.
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.
Cell. 184(1):120-132.e14 (2021)
- Yu Y, Scheel TKH, Luna JM, Chung H, Nishiuchi E, Scull MA, Echeverría N, Ricardo-Lax I, Kapoor A, Lipkin WI, Divers TJ, Antczak DF, Tennant BC, Rice CM.
miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.
PLoS Pathog. 13(10):e1006694 (2017)
- Luna JM, Barajas JM, Teng KY, Sun HL, Moore MJ, Rice CM, Darnell RB, Ghoshal K.
Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer.
Mol Cell. 67(3):400-410.e7. (2017)
- Billerbeck E, Wolfisberg R, Fahnøe U, Xiao JW, Quirk C, Luna JM, Cullen JM, Hartlage AS, Chiriboga L, Ghoshal K, Lipkin WI, Bukh J, Scheel TKH, Kapoor A, Rice CM.
Mouse models of acute and chronic hepacivirus infection.
Science. 357(6347):204-208 (2017)
- Scheel TK, Luna JM*, Liniger M*, Nishiuchi E, Rozen-Gagnon K, Shlomai A, Auray G, Gerber M, Fak J, Keller I, Bruggmann R, Darnell RB, Ruggli N, Rice CM.
A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration.
Cell Host Microbe. 19(3):409-23 (2016)
- Luna JM, Scheel TK, Danino T, Shaw KS, Mele A, Fak JJ, Nishiuchi E, Takacs CN, Catanese MT, de Jong YP, Jacobson IM, Rice CM, Darnell RB.
Hepatitis C virus RNA functionally sequesters miR-122.
Cell. 160(6):1099-110 (2015)