# Francisco J. Quintana

Francisco J. Quintana (born April 30, 1974) is an Argentinean-American immunologist and neuroscientist, and Professor of Neurology at Harvard Medical School. His lab studies interactions between the immune system and nervous system. He is best known for his work on the regulation of inflammation by astrocytes, and by the study of the role of the Aryl Hydrocarbon Receptor in the regulation of the immune response by pollutants, the microbial flora and metabolism. Dr. Quintana's research has implications for our understanding of the pathology of multiple inflammatory disorders including multiple sclerosis, Type 1 diabetes and Inflammatory Bowel Disease, and also brain tumors and infectious diseases. His work has also led to the development of novel therapeutic interventions, and novel techniques for the investigation of regulatory mechanisms involved in the control of inflammation, including RABID-seq (Clark et al, Science 2021), FIND-seq (Clark et al, Nature 2023) and SPEAC-seq (Wheeler et al, Science 2023).

## Education and career

Dr. Quintana received his Diploma in Biology from the University of Buenos Aires. He received his PhD in Immunology from the Weizmann Institute of Science in 2004, where he was advised by Dr. Irun Cohen. Dr. Quintana joined Brigham and Women's Hospital and Harvard Medical School as a postdoctoral fellow in 2005 where he was advised by Dr. Howard L. Weiner. In 2018, Dr. Quintana was appointed Professor of Neurology with tenure. Dr. Quintana is also an Associate Member of the Broad Institute of MIT and Harvard. Dr. Quintana is the Indirawati Kuchroo and Charlotte Weiner Distinguished Professor of Neuroimmunology (2021). Dr. Quintana is the president of International Society of Neuroimmunology (2021–2023).

## Research

Quintana's research investigates signaling pathways that control the immune response and neurodegeneration, with the ultimate goal of identifying novel therapeutic targets and biomarkers for immune-mediated disorders. Dr. Quintana has published over 230 peer reviewed articles and book chapters. Dr. Quintana's work identified important roles for the transcription factor AHR in the control of inflammation driven adaptive and innate immune cells. His work also identified important mechanisms that control neurodegeneration and provided the basis for the development of four biotechnology companies.

## Awards

Dr. Quintana has received multiple awards including the Lady Anne Chain Prize for Academic and Scientific Achievements (2004), the Junior Investigator Award from the National MS Society for Outstanding Research (2008), the NIH Pathway to Independence Award (2009), the Nature Publications Award for Outstanding Research Achievements (2009), the Harry Weaver Research Scholar Award (2014), the Harvard Medical School Young Mentor Award (2016), the Milestone in MS Research Award (2017), the American Association of Immunologists-BD Biosciences Investigator Award (2019), ISI Most Highly Cited List since 2019, the Barancik Prize for Innovation in MS Research (2020) and the Raices Award from the Republic of Argentina. Dr. Quintana is the Indirawati Kuchroo and Charlotte Weiner Distinguished Professor of Neuroimmunology (2021).

## Highlighted Articles

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 LM, Rone JM, Polonio CM, Fernandez Lahore G, Giovannoni F, Ferrara K, Gutierrez-Vazquez C, Li N, Sokolovska A, Plasencia A, Faust Akl C, Nanda P, Heck ES, Li Z, Lee HG, Chao CC, Rejano-Gordillo CM, Fonseca-Castro PH, Illouz T, Linnerbauer M, Kenison JE, Barilla RM, Farrenkopf D, Stevens NA, Piester G, Chung EN, Dailey L, Kuchroo VK, Hava D, Wheeler MA, Clish C, Nowarski R, Balsa E, Lora JM, Quintana FJ. Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells. Nature. 2023 Aug;620(7975):881-889.
31. Lee HG, Rone JM, Li Z, Akl CF, Shin SW, Lee JH, Flausino LE, Pernin F, Chao CC, Kleemann KL, Srun L, Illouz T, Giovannoni F, Charabati M, Sanmarco LM, Kenison JE, Piester G, Zandee SEJ, Antel J, Rothhammer V, Wheeler MA, Prat A, Clark IC, Quintana FJ. Disease-associated astrocyte epigenetic memory promotes CNS pathology. bioRxiv. Nature, In press.