Research Area
Dr. Quintana’s research is focused on Neuroimmunology to identify novel therapeutic targets for immune-mediated and neurodegenerative disorders. He has published over 230 peer reviewed articles and book chapters. Dr. Quintana’s work identified the transcription factor AHR as an important regulator of inflammation driven by adaptive and innate immune cells. He defined mechanisms by which cell-cell interactions, metabolism, the microbiome, and environmental chemicals control inflammation and neurodegeneration. His work guided the development of Tapinarof, the first FDA-approved AHR-targeting drug for psoriasis therapy. He has developed antigen microarrays for the monitoring of the immune response, novel approaches for the modulation of the immune response based on nucleic acids, nanoparticles, small molecules and engineered probiotics. In addition, he has developed novel approaches for the study of cell-cell interactions in vivo and in vitro, including RABID-seq, Find-seq and SPEAC-seq.
Team Description
The Quintana Lab is a multidisciplinary team of professionals from different fields of science who collaborate to solve complex problems in Neuroimmunology and with the common goals of identifying mechanisms of disease pathogenesis and developing novel therapeutic approaches. Our group includes about 20 scientists with expertise in immunology, neuroscience, medicine, bioengineering, computer science and molecular biology. These broad expertise allows us to use multidisciplinary approaches to address important questions in Neuroimmunology, usually involving the development of novel technologies (e.g. RABID-seq, SPEAC-seq) and experimental model (e.g. zebrafish models of tissue-specific inflammation). This multidisciplinary group of scientists works towards a common goal of improving human health and well-being through cutting-edge research and innovation.
Team Members
Team Show
Publications
1. Quintana, F.J., Gerber, D., Kent, S.C., Cohen, I.R. & Shai, Y. HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation. Journal of Clinical Investigation, 115(8), 2149-2158 (2005).
2. Quintana, F.J., Basso, A.S., Iglesias, A.H., Korn, T., Farez, M.F., Bettelli, E., Caccamo, M., Oukka, M. & Weiner, H.L. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature, 453(7191), 65-71 (2008).
3. *Farez, M.F., *Quintana F.J., Gandhi, R., Izquierdo, G., Lucas, M. & Weiner, H.L. TLR2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nature Immunology, 10(9), 958-964 (2009). Corresponding author.
4. Apetoh, L., Quintana, F. J., Pot, C., Joller, N., Xiao, S., Kumar, D., Burns, E. J., Sherr, D. H., Weiner, H. L. & Kuchroo, V. K. (2010). The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nature Immunology, 11(9), 854–861 (2010).
5. Gandhi R., Kumar D., Burns E.J., Nadeau M., Dake B., Laroni A., Kozoriz D., Weiner H.L. & Quintana F.J. Aryl hydrocarbon receptor activation induces human Tr1-like and Foxp3+ Treg cells. Nature Immunology, 11(9), 846-53 (2010).
6. Yeste, A., Nadeau, M., Burns, E.J., Weiner, H.L. & Quintana, F.J. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses EAE. Proc Natl Acad Sci U S A, 109(28), 11270-5 (2012).
7. *Quintana, F.J., *Jin, H., Burns, E.J., Nadeau, M., Yeste, A., Kumar, D., Rangachari, M., Zhu, C., Xiao, S., Seavitt, J., Georgopoulos, K. & Kuchroo, V.K. Aiolos promotes T(H)17 differentiation by directly silencing Il2 expression. Nature Immunology, 13(8), 770-777 (2012).
8. Mascanfroni, I.D., Yeste, A., Vieira, S.M., Burns, E.J., Patel, B., Sloma, I., Wu, Y., Mayo, L., Efroni, S., Kuchroo, V.K., Robson, S.C. & Quintana, F.J. IL-27 acts on dendritic cells to suppress the T-cell response and autoimmunity by inducing ENTPD1 (CD39) expression. Nature Immunology, 14(10), 1054-1063 (2013).
9. Yeste, A., Mascanfroni, I.D., Nadeau, M., Burns, E.J., Tukpah, A.M., Santiago, A., Wu, C., Patel, B., Kumar, D. & Quintana, F.J. IL-21 induces IL-22 production in CD4+ T cells. Nature Communications, 5, 3753 (2014).
10. Mayo L, Trauger S.A., Blain M., Nadeau M., Patel B., Alvarez J.I., Mascanfroni I.D., Yeste A., Kivisäkk P., Kallas K., Ellezam B., Bakshi R., Prat A., Antel J.P., Weiner H.L. & Quintana F.J. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nature Medicine, 20(10), 1147-1156 (2014).
11. Mascanfroni ID, Takenaka M.C., Yeste A., Patel B., Wu Y., Kenison J., Siddiqui S., Basso A.S., Otterbein L.E., Pardoll D.M., Pan F., Priel A., Clish C.B., Robson S.C. & Quintana F.J. Metabolic control of Tr1 cell differentiation by AHR and HIF1-α. Nature Medicine, 21(6), 638-646 (2015).
12. Farez, M.F., Mascanfroni, I.D., Méndez-Huergo, S., Yeste, A., Murugaiyan, G., Garo, L.P., Balbuena Aguirre, M.E., Patel, B., Ysrraelit, M.C., Zhu, C., Kuchroo, V.K., Rabinovich, G.A., *Quintana, F.J. & *Correale, J. Melatonin contributes to the seasonality of multiple sclerosis relapses. Cell, 162(6):1338-1352 (2015). Corresponding and lead author.
13. Yeste, A., Takenaka, M.C., Mascanfroni, I.D., Nadeau, M., Kenison, J.E., Patel, B., Tukpah, A.M., Babon, J.A., DeNicola, M., Kent, S.C., Pozo, D., & Quintana, F.J. (2016). Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Science signaling, 9(433), ra61 (2016).
14. Rothhammer, V., Mascanfroni, I.D., Bunse, L., Takenaka, M.C., Kenison, J.E., Mayo, L., Chao, C.C., Patel, B., Yan, R., Blain, M., Alvarez, J.I., Kébir, H., Anandasabapathy, N., Izquierdo, G., Jung, S., Obholzer, N., Pochet, N., Clish, C.B., Prinz, M., Prat, A., Antel, J. & Quintana, F.J. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nature medicine, 22(6), 586–597 (2016).
15. Rothhammer V., Borucki D.M., Tjon E.C., Takenaka M.C., Chao C.C., Ardura-Fabregat A., de Lima K.A., Gutiérrez-Vázquez C., Hewson P., Staszewski O., Blain M., Healy L., Neziraj T., Borio M., Wheeler M., Dragin L.L., Laplaud D.A., Antel J., Alvarez J.I., Prinz M. & Quintana F.J. Microglial control of astrocytes in response to microbial metabolites. Nature, 557, 724-728 (2018).
16. Takenaka M.C., Gabriely G., Rothhammer V., Mascanfroni I.D., Wheeler M.A., Chao C.C., Gutiérrez-Vázquez C., Kenison J., Tjon E.C., Barroso A., Vandeventer T., Alves de Lima K., Rothweiler S., Ghannam S., Zandee S., Healy L., Sherr D., Farez M. F., Pratt A., Antel J., Reardon D.A., Zhang H., Robson S.C., Getz G., Weiner H.L. & Quintana F.J.Control of tumor-associated macrophages and T-cells in glioblastoma via AHR and CD39. Nature Neuroscience, 22(5), 729-740 (2019).
17. Wheeler M.A., Jaronen M., Covacu R., Zandee S.E.J., Scalisi G., Rothhammer V., Tjon E.C., Chao C.C., Kenison J.E., Blain M., Rao V.T.S., Hewson P., Barroso A., Gutiérrez-Vázquez C., Prat A., Antel J.P., Hauser R. & Quintana F.J. Environmental control of astrocyte pathogenic activities in CNS inflammation. Cell, 176(3), 581-596 (2019).
18. Chao C.C., Gutiérrez-Vázquez C., Rothhammer V., Mayo L., Wheeler M.A., Tjon E.C., Zandee S.E.J., Blain M., Alves de Lima K., Takenaka M.C., Pacheco J.A., Hewson P., Liu L., Sanmarco L.M., Borucki D.M., Lipof G.Z., Trauger S.A., Clish C., Antel J., Prat A. & Quintana F.J. Metabolic control of astrocyte pathogenic activity via cPLA2-MAVS. Cell, 179(7), 1483-1498 (2019).
19. Wheeler, M. A., Clark, I.C., Tjon, E. C., Li, Z., Zandee, S.E.J., Couturier, C.P., Watson, B.R., Scalisi, G., Alkwai, S., Rothhammer, V., Rotem, A., Heyman, J.A., Thaploo, S., Sanmarco, L.M., Ragoussis, J., Weitz, D. A., Petrecca, K., Moffitt, J.R., Becher, B., Antel, J.P., Prat, A. & Quintana, F.J. (2020). MAFG-driven astrocytes promote CNS inflammation. Nature, 578(7796), 593–599 (2020).
20. Kenison, J.E., Jhaveri, A., Li, Z., Khadse, N., Tjon, E., Tezza, S., Nowakowska, D., Plasencia, A., Stanton, V.P., Jr., Sherr, D.H., & Quintana, F.J. Tolerogenic nanoparticles suppress central nervous system inflammation. Proc Natl Acad Sci U S A, 117(50), 32017-32028 (2020).
21. Giovannoni F., Bosch I., Polonio M.C., Torti M.F., Wheeler M.A., Li Z., Romorini L., Rodriguez Varela M.S., Rothhammer V., Barroso A., Tjon E. C., Sanmarco L. M., Takenaka M.C, Modaresi S., Gutiérrez-Vázquez C., Ghabdan Zanluqui N., Barreto dos Santos N., Demarchi Munhoz C., Wang Z., Damonte E.B., Sherr D., Gehrke L., Schatzmann Peron J.P., Garcia C.G. & Quintana F.J. AHR is a Zika virus host factor and a candidate target for antiviral therapy. Nature Neuroscience, 23(8), 939-951 (2020).
22. Wheeler M.A., Clark I.C., Tjon E.C., Li Z., Zandee S.E.J., Couturier C.P., Watson B.R., Scalisi G., Alkwai S., Rothhammer V., Rotem A., Heyman J.A., Thaploo S., Sanmarco L.M., Ragoussis J., Weitz D., Petrecca K., Moffitt J.R., Becher B., Antel J.P., Prat A. & Quintana F.J. Genomic control of astrocytes in multiple sclerosis. Nature, 578, 593-599 (2020).
23. Scott, B. M., Gutiérrez-Vázquez, C., Sanmarco, L. M., da Silva Pereira, J. A., Li, Z., Plasencia, A., Hewson, P., Cox, L. M., O'Brien, M., Chen, S. K., Moraes-Vieira, P. M., Chang, B. S. W., Peisajovich, S. G., & Quintana, F. J. (2021). Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease. Nature Medicine, 27(7), 1212–1222 (2021).
24. Sanmarco, L. M., Wheeler, M. A., Gutiérrez-Vázquez, C., Polonio, C. M., Linnerbauer, M., Pinho-Ribeiro, F. A., Li, Z., Giovannoni, F., Batterman, K. V., Scalisi, G., Zandee, S., Heck, E. S., Alsuwailm, M., Rosene, D. L., Becher, B., Chiu, I. M., Prat, A. & Quintana, F.J. Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature, 590(7846), 473–479 (2021).
25. Clark, I. C., Gutiérrez-Vázquez, C., Wheeler, M.A., Li, Z., Rothhammer, V., Linnerbauer, M., Sanmarco, L.M., Guo, L., Blain, M., Zandee, S., Chao, C.C., Batterman, K.V., Schwabenland, M., Lotfy, P., Tejeda-Velarde, A., Hewson, P., Manganeli Polonio, C., Shultis, M.W., Salem, Y., Tjon, E.C., Fonseca-Castro, P.H., Borucki, D.M., Alves de Lima, K., Plasencia, A., Abate, A.R., Rosene, D.L., Hodgetts, K.J., Prinz, M., Antel, J.P., Prat, A. & Quintana, F.J. Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science, 372(6540), (2021).
26. Sanmarco L.M., Chao C.C., Wang Y.C., Kenison J.E., Li Z., Rone J.M., Rejano-Gordillo C.M., Polonio C.M., Gutierrez-Vazquez C., Piester G., Plasencia A., Li L., Giovannoni F., Lee H.G., Faust Akl C., Wheeler M.A., Mascanfroni I., Jaronen M., Alsuwailm M., Hewson P., Yeste A., Andersen B.M., Franks D.G., Huang C.J., Ekwudo M., Tjon E.C., Rothhammer V., Takenaka M., de Lima K.A., Linnerbauer M., Guo L., Covacu R., Queva H., Fonseca-Castro P.H., Bladi M.A., Cox L.M., Hodgetts K.J., Hahn M.E., Mildner A., Korzenik J., Hauser R., Snapper S.B. & Quintana, F. J. (2022). Identification of environmental factors that promote intestinal inflammation. Nature, 611(7937), 801–809 (2022).
27. Clark I.C., Mudvari P., Thaploo S., Smith S., Abu-Laban M., Hamouda M., Theberge M., Shah S., Ko S.H., Pérez L., Bunis D.G., Lee J.S., Kilam D., Zakaria S., Choi S., Darko S., Henry A.R., Wheeler M.A., Hoh R., Butrus S., Deeks S.G., Quintana F.J., Douek D.C., Abate A.R. & Boritz E.A. (2023). HIV silencing and cell survival signatures in infected T cell reservoirs. Nature, 614(7947), 318–325 (2023).
28. Clark I.C., Wheeler M.A., Lee H.G., Li Z., Sanmarco L.M., Thaploo S., Polonio C.M., Shin S.W., Scalisi G., Henry A.R., Rone J.M., Giovannoni F., Charabati M., Akl C.F., Aleman D.M., Zandee S.E.J., Prat A., Douek D.C., Boritz E.A., Quintana F.J., Abate A.R. (2023). Identification of astrocyte regulators by nucleic acid cytometry. Nature, 614(7947), 326–333 (2023).
29. Wheeler M.A., Clark I.C., Lee H.G., Li Z., Linnerbauer M., Rone J.M., Blain M., Akl C.F., Piester G., Giovannoni F., Charabati M., Lee J.H., Kye Y.C., Choi J., Sanmarco L.M., Srun L., Chung E.N., Flausino L.E., Andersen B.M., Rothhammer V., Yano H., Illouz T., Zandee S.E.J., Daniel C., Artis D., Prinz M., Abate A.R., Kuchroo V.K., Antel J.P., Prat A., Quintana F.J. Droplet-based forward genetic screening of astrocyte-microglia cross-talk. Science, 379(6636), 1023–1030 (2023).
30. *Sanmarco, L.M., Rone, J.M., Polonio, C.M., Gutierrez-Vazquez, C., Li, N., Sokolovska, A., Plasencia, A., Ferrara, K., Giovannoni, F., Faust Akl, C., Nanda, P., Heck, E.S., Li, Z., Lee, H.G., Chao, C.C., Rejano-Gordillo, C.M., Fonseca-Castro, P.H., Linnerbauer, M., Kenison, J.E., Barilla, R.M., Wheeler, M.A., Piester, G., Dailey, L., Kuchroo, V.K., Hava, D., Clish, C., Nowarski, R., Lora, J.M., Quintana, F. J. Quintana, F.J. (2023). Engineered probiotics limit CNS autoimmunity by modulating dendritic cell metabolism. Nature, in press.