Patrick Hogan (biologist)

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Patrick G. Hogan is a cellular and molecular biologist who studies how cellular signaling leads to gene expression. He obtained his bachelor’s degree from Harvard University and a PhD in neurobiology from Harvard Medical School. In 2010, he moved to the La Jolla Institute for Immunology in San Diego as a Professor in the Division of Signaling and Gene Expression.[1] He is a Founder and Member of the Scientific Advisory Board, CalciMedica Inc, La Jolla, CA.[2]

Research[edit]

Hogan's research interests have been focused on the signaling and gene expression pathways that result from calcium entry into cells. He molecularly cloned the transcription factor NFAT, which is dephosphorylated by the calcium-regulated phosphatase calcineurin,[3] and solved its structure in collaboration with the laboratory of Stephen Harrison at Harvard Medical School.[4][5] He investigated the protein-protein interactions between calcineurin and NFAT.[6][7] Subsequently, he identified ORAI1 as the pore subunit of the store-operated Ca2+ channel in human cells,[8] and investigated the regulation of ORAI1 by STIM1,[9][10] a single-pass transmembrane protein located in the membrane of the endoplasmic reticulum (ER) that senses the concentration of calcium in the ER stores and then opens the ORAI1 calcium channel in the plasma membrane.[11] He has made major contributions to our understanding of the mechanisms and regulation of cellular calcium signaling, particularly modulation of the STIM-ORAI pathway in the context of ER-plasma membrane junctions, which he has investigated using whole-genome screens, super-resolution microscopy and single-molecule tracking.[12][13][14]

T cells that enter a tumor initially attempt to destroy the cancer cells but then enter a state in which they are poorly responsive and fail to attack the tumor cells effectively. This state also occurs during chronic viral infections and has been termed “T cell exhaustion.”[15] Hogan's research showed that T cell exhaustion is driven by the transcription factor NFAT in the absence of its transcriptional partners Fos and Jun.[16] With Fos and Jun, NFAT promotes effective T cell activation and tumor killing, but in their absence, NFAT induces the secondary transcription factors NR4A and TOX, which then cooperate with NFAT to induce the exhausted or hyporesponsive state.[17][18] He also showed that BATF transcription factors play an important role in preventing the exhaustion of T cells with Chimeric Antigen Receptors (CAR),[19] and that disruption of the NFAT:AP-1 interaction can be achieved with small molecules and may be a promising therapeutic approach.[20]

References[edit]

  1. ^ "Hogan Lab". La Jolla Institute for Immunology. Retrieved 2022-04-04.
  2. ^ Fiona (2021-04-08). "Company History | CalciMedica". Retrieved 2022-04-04.
  3. ^ McCaffrey, P. G.; Luo, C.; Kerppola, T. K.; Jain, J.; Badalian, T. M.; Ho, A. M.; Burgeon, E.; Lane, W. S.; Lambert, J. N.; Curran, T. (1993-10-29). "Isolation of the cyclosporin-sensitive T cell transcription factor NFATp". Science. 262 (5134): 750–754. Bibcode:1993Sci...262..750M. doi:10.1126/science.8235597. ISSN 0036-8075. PMID 8235597.
  4. ^ Chen, L.; Glover, J. N.; Hogan, P. G.; Rao, A.; Harrison, S. C. (1998-03-05). "Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA". Nature. 392 (6671): 42–48. Bibcode:1998Natur.392...42C. doi:10.1038/32100. ISSN 0028-0836. PMID 9510247. S2CID 4305535.
  5. ^ Hogan, Patrick G.; Chen, Lin; Nardone, Julie; Rao, Anjana (2003-09-15). "Transcriptional regulation by calcium, calcineurin, and NFAT". Genes & Development. 17 (18): 2205–2232. doi:10.1101/gad.1102703. ISSN 0890-9369. PMID 12975316.
  6. ^ Aramburu, J.; Yaffe, M. B.; López-Rodríguez, C.; Cantley, L. C.; Hogan, P. G.; Rao, A. (1999-09-24). "Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A". Science. 285 (5436): 2129–2133. doi:10.1126/science.285.5436.2129. ISSN 0036-8075. PMID 10497131.
  7. ^ Li, Huiming; Rao, Anjana; Hogan, Patrick G. (2011). "Interaction of calcineurin with substrates and targeting proteins". Trends in Cell Biology. 21 (2): 91–103. doi:10.1016/j.tcb.2010.09.011. ISSN 0962-8924. PMC 3244350. PMID 21115349.
  8. ^ Prakriya, Murali; Feske, Stefan; Gwack, Yousang; Srikanth, Sonal; Rao, Anjana; Hogan, Patrick G. (2006-09-14). "Orai1 is an essential pore subunit of the CRAC channel". Nature. 443 (7108): 230–233. Bibcode:2006Natur.443..230P. doi:10.1038/nature05122. ISSN 1476-4687. PMID 16921383. S2CID 4310221.
  9. ^ Zhou, Yubin; Meraner, Paul; Kwon, Hyoung T; Machnes, Danya; Oh-hora, Masatsugu; Zimmer, Jochen; Huang, Yun; Stura, Antonio; Rao, Anjana; Hogan, Patrick G (2010). "STIM1 gates the store-operated calcium channel ORAI1 in vitro". Nature Structural & Molecular Biology. 17 (1): 112–116. doi:10.1038/nsmb.1724. ISSN 1545-9993. PMC 2902271. PMID 20037597.
  10. ^ Zhou, Yubin; Srinivasan, Prasanna; Razavi, Shiva; Seymour, Sam; Meraner, Paul; Gudlur, Aparna; Stathopulos, Peter B; Ikura, Mitsuhiko; Rao, Anjana; Hogan, Patrick G (2013). "Initial activation of STIM1, the regulator of store-operated calcium entry". Nature Structural & Molecular Biology. 20 (8): 973–981. doi:10.1038/nsmb.2625. ISSN 1545-9993. PMC 3784406. PMID 23851458.
  11. ^ Hogan, Patrick G.; Lewis, Richard S.; Rao, Anjana (2010-04-23). "Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI". Annual Review of Immunology. 28: 491–533. doi:10.1146/annurev.immunol.021908.132550. ISSN 0732-0582. PMC 2861828. PMID 20307213.
  12. ^ Sharma, Sonia; Quintana, Ariel; Findlay, Gregory M; Mettlen, Marcel; Baust, Beate; Jain, Mohit; Nilsson, Roland; Rao, Anjana; Hogan, Patrick G (2013-07-11). "An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry". Nature. 499 (7457): 238–242. Bibcode:2013Natur.499..238S. doi:10.1038/nature12229. ISSN 0028-0836. PMC 3846693. PMID 23792561.
  13. ^ Quintana, Ariel; Rajanikanth, Vangipurapu; Farber-Katz, Suzette; Gudlur, Aparna; Zhang, Chen; Jing, Ji; Zhou, Yubin; Rao, Anjana; Hogan, Patrick G. (2015-12-22). "TMEM110 regulates the maintenance and remodeling of mammalian ER–plasma membrane junctions competent for STIM–ORAI signaling". Proceedings of the National Academy of Sciences of the United States of America. 112 (51): E7083–E7092. Bibcode:2015PNAS..112E7083Q. doi:10.1073/pnas.1521924112. ISSN 0027-8424. PMC 4697383. PMID 26644574.
  14. ^ Katz, Zachary B.; Zhang, Chen; Quintana, Ariel; Lillemeier, Björn F.; Hogan, Patrick G. (2019-07-25). "Septins organize endoplasmic reticulum-plasma membrane junctions for STIM1-ORAI1 calcium signalling". Scientific Reports. 9 (1): 10839. Bibcode:2019NatSR...910839K. doi:10.1038/s41598-019-46862-w. ISSN 2045-2322. PMC 6658532. PMID 31346209.
  15. ^ Blank, Christian U.; Haining, W. Nicholas; Held, Werner; Hogan, Patrick G.; Kallies, Axel; Lugli, Enrico; Lynn, Rachel C.; Philip, Mary; Rao, Anjana; Restifo, Nicholas P.; Schietinger, Andrea (2019). "Defining 'T cell exhaustion'". Nature Reviews. Immunology. 19 (11): 665–674. doi:10.1038/s41577-019-0221-9. ISSN 1474-1741. PMC 7286441. PMID 31570879.
  16. ^ Martinez, Gustavo J.; Pereira, Renata M.; Äijö, Tarmo; Kim, Edward Y.; Marangoni, Francesco; Pipkin, Matthew E.; Togher, Susan; Heissmeyer, Vigo; Zhang, Yi Chen; Crotty, Shane; Lamperti, Edward D. (2015-02-17). "The transcription factor NFAT promotes exhaustion of activated CD8+ T cells". Immunity. 42 (2): 265–278. doi:10.1016/j.immuni.2015.01.006. ISSN 1074-7613. PMC 4346317. PMID 25680272.
  17. ^ Mognol, Giuliana P.; Spreafico, Roberto; Wong, Victor; Scott-Browne, James P.; Togher, Susan; Hoffmann, Alexander; Hogan, Patrick G.; Rao, Anjana; Trifari, Sara (2017-03-28). "Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells". Proceedings of the National Academy of Sciences of the United States of America. 114 (13): E2776–E2785. doi:10.1073/pnas.1620498114. ISSN 1091-6490. PMC 5380094. PMID 28283662.
  18. ^ Seo, Hyungseok; Chen, Joyce; González-Avalos, Edahí; Samaniego-Castruita, Daniela; Das, Arundhoti; Wang, Yueqiang H.; López-Moyado, Isaac F.; Georges, Romain O.; Zhang, Wade; Onodera, Atsushi; Wu, Cheng-Jang (2019-06-18). "TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion". Proceedings of the National Academy of Sciences of the United States of America. 116 (25): 12410–12415. doi:10.1073/pnas.1905675116. ISSN 1091-6490. PMC 6589758. PMID 31152140.
  19. ^ Seo, Hyungseok; González-Avalos, Edahí; Zhang, Wade; Ramchandani, Payal; Yang, Chao; Lio, Chan-Wang J.; Rao, Anjana; Hogan, Patrick G. (2021). "BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells". Nature Immunology. 22 (8): 983–995. doi:10.1038/s41590-021-00964-8. ISSN 1529-2916. PMC 8319109. PMID 34282330.
  20. ^ Mognol, Giuliana P.; González-Avalos, Edahí; Ghosh, Srimoyee; Spreafico, Roberto; Gudlur, Aparna; Rao, Anjana; Damoiseaux, Robert; Hogan, Patrick G. (2019-05-14). "Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor". Proceedings of the National Academy of Sciences of the United States of America. 116 (20): 9959–9968. doi:10.1073/pnas.1820604116. ISSN 1091-6490. PMC 6525529. PMID 31019078.
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