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HS is characterized by heterogenous molecular changes that are poorly understood, posing a significant challenge for drug development. Therapeutic options remain limited, and many patients experience disease relapse despite treatment. Therefore, precision medicine approaches are urgently needed to identify new therapies for HS. Here, we combine integrative transcriptomics, large-scale drug perturbational datasets, and translational immunology to identify sirolimus, pioglitazone, and fulvestrant as novel therapies for HS that can directly target and reverse the HS disease gene signature in immune cell types relevant to HS pathogenesis. Using a novel\n                  <jats:italic>ex vivo<\/jats:italic>\n                  HS skin model, sirolimus, pioglitazone, and fulvestrant inhibited T cell proliferation and activation, and suppressed the production of pro-inflammatory cytokines from HS skin. These results show that unbiased data-driven precision medicine approaches can identify novel therapies for HS and can serve more generally as a model approach for therapeutic discovery in other chronic inflammatory diseases.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Data-driven precision medicine approach identifies sirolimus, pioglitazone, and fulvestrant as novel therapies for hidradenitis suppurativa<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.23.706050","type":"posted-content","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:40:17Z","timestamp":1771994417000},"source":"Crossref","is-referenced-by-count":0,"title":["Computational discovery of precision therapeutics for hidradenitis suppurativa"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5144-2552","authenticated-orcid":false,"given":"Ernest Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"},{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States"},{"name":"Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Leboit","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley B.","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice S.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States"},{"name":"Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Vallania","sequence":"additional","affiliation":[{"name":"immunoLogic, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E.","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Klufas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Connecticut, Farmington, CT, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Surgery, UCSF, San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sirota","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States"},{"name":"Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026022713002384000_2026.02.23.706050v1.1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis suppurativa","volume":"6","year":"2020","journal-title":"Nat. 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