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.
Research Information
Research Interests
The Luna Lab's long-term vision is to decode the multifaceted roles of RNA-binding proteins (RBPs) in orchestrating gene expression across diverse biological contexts. We investigate how RBPs influence viral infections and cellular stress responses at cellular and subcellular levels. Using positive-sense RNA viruses as models, we explore how RBPs orchestrate viral replication and modulate innate immune responses.
Our interdisciplinary approach spans genomics, transcriptomics, proteomics, and molecular virology to dissect the intricate dynamics of RBP:RNA interaction networks at a systems level. We develop and apply cutting-edge technologies to identify and functionally characterize RBP:RNA interactions in disease-relevant cellular models, providing insights into viral replication mechanisms, host responses, and the molecular underpinnings of pathogenesis.
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
Current research projects include:
1) Mapping Subcellular RBP:RNA Interactions: We're developing innovative tools to capture and analyze RBP:RNA interactions with unprecedented subcellular resolution. By biochemically preserving spatial information in living cells, we aim to uncover how these interactions are organized within specific cellular structures such as stress granules, P-bodies, and viral replication organelles. This project provides crucial insights into how RBPs operate in distinct cellular locations and how their spatial distribution affects RNA metabolism and viral infections.
2) RBP Dynamics in Viral Infections: Building on our work with hepatitis C virus (HCV) and SARS-CoV-2, we study how cellular RBPs balance viral genome replication, translation, and virion assembly. We use viral reverse genetics, CRISPR screening, and advanced RNA profiling to map the dynamic interactions between viral genomes and host RBPs throughout the infection cycle. Our goal is to unravel the regulatory logic of RBPs during infection, informing the development of novel antivirals and RNA-based therapies.
3) RBP Networks in Innate Immunity: We combine experimental data with state-of-the-art bioinformatics to model RBP activities during innate immune responses. By analyzing how RBP:RNA interactions change across various cellular domains during infection, we aim to predict key regulatory nodes and vulnerabilities in host-pathogen interactions. This work bridges our experimental efforts with a systems-level understanding of RNA regulation.
Please visit the Luna lab site for more information.
Publications
- Yi S, Singh SS, Rozen-Gagnon K, Luna JM. Mapping RNA-protein interactions with subcellular resolution using colocalization CLIP. RNA. 2024 Jun 17;30(7):920-937. doi: 10.1261/rna.079890.123. PMID: 38658162
- 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) PMID: 34648371 *co-first author
- 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) PMID: 34170927
- 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) PMID: 33794184
- 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) PMID: 33357464 *co-first author
- 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) PMID: 33382968 *co-first author
- 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) PMID: 29084265
- 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) PMID: 28735896
- 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) PMID: 28706073
- 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) PMID: 26962949 *contributed equally
- 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) PMID: 25768906