Gabriela Fragiadakis, PhD

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Gabriela Fragiadakis, PhD

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CFAR Bioinformatics Subcore Co-Director
Assistant Professor, School of Medicine
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Biography

I lead a computational immunology lab studying states of the human immune system across disease contexts using single-cell methods and data integration. We work with a variety of data types, including bulk- and single-cell sequencing and CyTOF. My research program is built from a foundation of collaborations as Director of the Data Science CoLab. Through CoLabs I have established partnerships to study systems-level immunity in viral infection, cancer, autoimmunity, and steady-state. From these projects I then pursue questions in immune phenotypes across contexts using high-dimensional analysis, data integration, and novel computational methods. In addition, I study immune-microbiome interactions at steady-state and in response to perturbation. In the lab we have a sub-team that builds and develops the UCSF Data Library project, a web-based platform to store, curate, share and analyze high-dimensional data.
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  1. Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP. SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants. Stem Cell Reports. 2023 Feb 08.
  2. Mennillo E, Kim YJ, Rusu I, Lee G, Dorman LC, Bernard-Vazquez F, Bain JL, Patel R, Andersen C, Rao A, Tamaki S, Tsui J, Shen A, Naser M, Eckalbar W, Cho SJ, Beck K, El-Nachef N, Lewin S, Selvig DR, Terdiman JP, Mahadevan U, Oh DY, Fragiadakis GK, Pisco A, Combes AJ, Kattah MG. Single-cell and spatial multi-omics identify innate and stromal modules targeted by anti-integrin therapy in ulcerative colitis. bioRxiv. 2023 Jan 22.
  3. Wastyk HC, Perelman D, Topf M, Fragiadakis GK, Robinson JL, Sonnenburg JL, Gardner CD, Sonnenburg ED. Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet. Gut Microbes. 2023 Jan-Dec; 15(1):2178794.
  4. Li X, Perelman D, Leong AK, Fragiadakis G, Gardner CD, Snyder MP. Distinct factors associated with short-term and long-term weight loss induced by low-fat or low-carbohydrate diet intervention. Cell Rep Med. 2022 12 20; 3(12):100870.
  5. Belonwu SA, Li Y, Bunis DG, Rao AA, Solsberg CW, Oskotsky T, Taubes AL, Grone B, Zalocusky KA, Fragiadakis GK, Huang Y, Sirota M. Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets Reveals APOE Genotype-Specific Changes Across Cell Types in Two Brain Regions. Front Aging Neurosci. 2022; 14:749991.
  6. Fragiadakis GK, Bjornson-Hooper ZB, Madhireddy D, Sachs K, Chen H, McIlwain DR, Spitzer MH, Bendall SC, Nolan GP. Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types. Front Immunol. 2022; 13:867016.
  7. Bjornson-Hooper ZB, Fragiadakis GK, Spitzer MH, Chen H, Madhireddy D, Hu K, Lundsten K, McIlwain DR, Nolan GP. A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates. Front Immunol. 2022; 13:867015.
  8. Combes AJ, Samad B, Tsui J, Chew NW, Yan P, Reeder GC, Kushnoor D, Shen A, Davidson B, Barczak AJ, Adkisson M, Edwards A, Naser M, Barry KC, Courau T, Hammoudi T, Argüello RJ, Rao AA, Olshen AB, Immunoprofiler Consortium, Cai C, Zhan J, Davis KC, Kelley RK, Chapman JS, Atreya CE, Patel A, Daud AI, Ha P, Diaz AA, Kratz JR, Collisson EA, Fragiadakis GK, Erle DJ, Boissonnas A, Asthana S, Chan V, Krummel MF. Discovering dominant tumor immune archetypes in a pan-cancer census. Cell. 2022 01 06; 185(1):184-203.e19.
  9. Belonwu SA, Li Y, Bunis D, Rao AA, Solsberg CW, Tang A, Fragiadakis GK, Dubal DB, Oskotsky T, Sirota M. Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions. Mol Neurobiol. 2022 Jan; 59(1):276-293.
  10. Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez-Fuertes M, Wang X, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Poller W, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine. 2021 Oct; 40:101099.
  11. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Le Voyer T, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ, UCSF COMET consortium . Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Sci Transl Med. 2021 09 22; 13(612):eabh2624.
  12. Wang VE, Blaser BW, Patel RK, Behbehani GK, Rao AA, Durbin-Johnson B, Jiang T, Logan AC, Settles M, Mannis GN, Olin R, Damon LE, Martin TG, Sayre PH, Gaensler KM, McMahon E, Flanders M, Weinberg V, Ye CJ, Carbone DP, Munster PN, Fragiadakis GK, McCormick F, Andreadis C. Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. Blood Cancer Discov. 2021 09; 2(5):434-449.
  13. Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 08 05; 184(16):4137-4153.e14.
  14. Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP. SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator. bioRxiv. 2021 Jun 02.
  15. Hendley AM, Rao AA, Leonhardt L, Ashe S, Smith JA, Giacometti S, Peng XL, Jiang H, Berrios DI, Pawlak M, Li LY, Lee J, Collisson EA, Anderson MS, Fragiadakis GK, Yeh JJ, Ye CJ, Kim GE, Weaver VM, Hebrok M. Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree. Elife. 2021 05 19; 10.
  16. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Voyer TL, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, UCSF COMET consortium , Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ. Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19. bioRxiv. 2021 Mar 10.
  17. Chan V, Gherardini PF, Krummel MF, Fragiadakis GK. A "data sharing trust" model for rapid, collaborative science. Cell. 2021 02 04; 184(3):566-570.
  18. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Chew NW, Cleary SJ, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Im KW, Serwas NK, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, UCSF COMET Consortium, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF. Global absence and targeting of protective immune states in severe COVID-19. Nature. 2021 03; 591(7848):124-130.
  19. Bunis DG, Andrews J, Fragiadakis GK, Burt TD, Sirota M. dittoSeq: Universal User-Friendly Single-Cell and Bulk RNA Sequencing Visualization Toolkit. Bioinformatics. 2020 Dec 12.
  20. Rahil Z, Leylek R, Schürch CM, Chen H, Bjornson-Hooper Z, Christensen SR, Gherardini PF, Bhate SS, Spitzer MH, Fragiadakis GK, Mukherjee N, Kim N, Jiang S, Yo J, Gaudilliere B, Affrime M, Bock B, Hensley SE, Idoyaga J, Aghaeepour N, Kim K, Nolan GP, McIlwain DR. Landscape of coordinated immune responses to H1N1 challenge in humans. J Clin Invest. 2020 11 02; 130(11):5800-5816.
  21. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF. Global Absence and Targeting of Protective Immune States in Severe COVID-19. bioRxiv. 2020 Oct 29.
  22. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, UCSF COMET Consortium, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF. Global Absence and Targeting of Protective Immune States in Severe COVID-19. Res Sq. 2020 Oct 28.
  23. Fragiadakis GK, Wastyk HC, Robinson JL, Sonnenburg ED, Sonnenburg JL, Gardner CD. Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight. Am J Clin Nutr. 2020 06 01; 111(6):1127-1136.
  24. Ko ME, Williams CM, Fread KI, Goggin SM, Rustagi RS, Fragiadakis GK, Nolan GP, Zunder ER. FLOW-MAP: a graph-based, force-directed layout algorithm for trajectory mapping in single-cell time course datasets. Nat Protoc. 2020 02; 15(2):398-420.
  25. Bongen E, Lucian H, Khatri A, Fragiadakis GK, Bjornson ZB, Nolan GP, Utz PJ, Khatri P. Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection. Cell Rep. 2019 11 12; 29(7):1961-1973.e4.