Research
Learning from patients to understand mechanisms of resistance and unlock more effective T cell therapy designs.
Our overarching goal is to lay the foundations for a clinically informed T cell design through machine learning algorithms, eventually enabling artificial intelligence (AI) systems to nominate specific genetic edits for improved clinical outcomes in a given disease. We leverage innovation in machine learning and clinical multi-omic T cell therapy datasets to build AI systems at scale to enable broad generalization.
We collaborate broadly with physicians and scientists in the Cancer Cell Therapy Program, Cellular Immune Tolerance Program, computer science labs, experimental T cell therapy labs, and teams beyond Stanford on the analysis of primary clinical and preclinical multi-omic datasets. This work serves as the basis for training T cell therapy AI models at scale, which in turn inform our preclinical T cell designs. We integrate insights from the literature with insights from the data and models to build and test advanced T cell designs in the lab leveraging preclinical models that recapitulate resistance mechanisms observed in patients.
Selected Publications
Good Z*, Spiegel JY*, Sahaf B, Malipatlolla MB, Ehlinger ZJ, Kurra S, Desai MH, Reynolds WD, Wong Lin A, Vandris P, Wu F, Prabhu S, Hamilton MP, Tamaresis JS, Hanson PJ, Patel S, Feldman SA, Frank MJ, Baird JH, Muffly L, Claire GK, Craig J, Kong KA, Wagh D, Coller J, Bendall SC, Tibshirani RJ, Plevritis SK, Miklos DB§, Mackall CL§. (2022). Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy. Nature Medicine, 28(9): 1860-1871. PMID: 36097223.
Good Z, Glanville G, Gee MH, Davis MM, Khatri P. (2019). Computational and systems immunology: a students’ perspective. Trends in Immunology, 40(8): 665-8. PMID: 31288986.
https://www.sciencedirect.com/science/article/pii/S1471490619301292
[CSI-Perspective-TrendsImm-2019.pdf]
Good Z, Borges L, Vivanco Gonzalez N, Sahaf B, Samusik N, Tibshirani R, Nolan GP§, Bendall SC§. (2019). Proliferative tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells. Nature Biotechnology, 37(3): 259-66. PMID: 30742126.
Good Z*, Sarno J*, Jager A, Samusik N, Aghaeepour N, Simonds EF, While L, Lacayo NJ, Fantl WJ, Fazio G, Gaipa G, Biondi A, Tibshirani R, Bendall SC, Nolan GP§, Davis KL§. (2018). Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nature Medicine, 24(4): 474-83. PMID: 29505032.
Other Publications
All Publications
· Hamilton MP*, Sugio T*, Noordenbos T*, Shi S, Bulterys PL, Long Liu C, Olsen MN, Good Z, Dahiya S, Frank MJ, Sahaf B, Mackall CL, Gratzinger D, Diehn M, Alizadeh AA§, Miklos DB§. (2024). Risk of second malignancies & T-cell lymphoma after chimeric antigen receptor T-cell therapy. New England Journal of Medicine, 390(22): 2047-2060. PMID: 38865660.
https://www.nejm.org/doi/full/10.1056/NEJMoa2401361
· Yamada-Hunter SA*, Theruvath J*, Radosevich MT, McIntosh BJ, Freitas KA, Leruste A, Dhingra S, Martinez-Velez N, Mount CW, Sotillo E, Xu P, Delaidelli A, Desai MH, Sahaf B, Good Z, Labanieh L, Heitzeneder S, Banuelos A, Khan O, Marjon KD, Huang J, Wasserman SL, Spiegel JY, Sorensen PH, Monje M, Majzner RG, Weissman IL, Cochran JR, Mackall CL. (2024). Selective phagocytosis of tumor cells while sparing T cells using engineered CD47 enhances antitumor immunity. Nature, 630(8016):457-465. PMID: 38750365.
https://www.nature.com/articles/s41586-024-07443-8
· Hamilton MP, Craig E, Gentille Sanchez C, Mina A, Tamaresis J, Kirmani N, Ehlinger Z, Syal S, Good Z, Sworder B, Schroers-Martin J, Lu Y, Muffly L, Negrin R, Arai S, Lowsky R, Meyer E, Rezvani A, Shizuru J, Weng W, Shiraz P, Sidana S, Bharadwaj S, Smith M, Dahiya S, Sahaf B, Kurtz D, Mackall C, Tibshirani R, Alizadeh A, Frank M, Miklos D. (2024). CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity. Blood Advances, 8(12):3314-3326. PMID: 38498731.
· Alvarez-Breckenridge C, Anderson, KG, Correia AL, Demehri S, Dinh HQ, Dixon KO, Dunn GP, Evgin L, Goc J, Good Z, Hacohen N§, Han P, Hanč P, Hickey JW, Kersten K, Liu BC, Buqué A, Mao Y, Milner JJ, Pritykin Y, Pucci F, Scharping NE, Sudmeier L, Wang Y, Wieland A, Williams MW. (2023). Lessons for the next generation of scientists from the 2nd annual Arthur and Sandra Irving Cancer Immunology Symposium. Cancer Immunology Research, 11(12): 1571-1577. PMID: 37906619.
· Good Z*, Spiegel JY*, Sahaf B, Malipatlolla MB, Ehlinger ZJ, Kurra S, Desai MH, Reynolds WD, Wong Lin A, Vandris P, Wu F, Prabhu S, Hamilton MP, Tamaresis JS, Hanson PJ, Patel S, Feldman SA, Frank MJ, Baird JH, Muffly L, Claire GK, Craig J, Kong KA, Wagh D, Coller J, Bendall SC, Tibshirani RJ, Plevritis SK, Miklos DB§, Mackall CL§. (2022). Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy. Nature Medicine, 28(9): 1860-1871. PMID: 36097223.
https://www.nature.com/articles/s41591-022-01960-7
· Majzner RG*, Ramakrishna S*, Yeom KW, Patel S, Chinnasamy H, Schultz LM, Richards RM, Barsan V, Mancusi R, Geraghty AC, Good Z, Mochizuki A, Gillespie SM, Martin A, Toland S, Mahdi J, Reschke A, Chau I, Nie E, Chau AJ, Rotiroti MC, Mount CW, Baggott C, Mavroukakis S, Egeler E, Moon J, Erickson C, Green S, Kunicki M, Fujimoto M, Ehlinger Z, Reynolds W, Kurra S, Warren KE, Prabhu S, Vogel H, Rasmussen L, Cornell TT, Partap S, Fisher PG, Campen CJ, Filbin M, Grant G, Sahaf B, Davis KL, Feldman SA, Mackall CL§, Monje M§. (2022). GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature, 603(7903): 934-941. PMID: 35130560.
https://www.nature.com/articles/s41586-022-04489-4
· Zhang W, Li I, Reticker-Flynn NE, Good Z, Chang S, Samusik N, Saumyaa S, Li Y, Zhou X, Liang R, Kong CS, Le QT, Gentles AJ, Sunwoo JB, Nolan GP, Engleman EG, Plevritis SK. (2022). Identification of cell types in multiplexed in situ images by combining protein expression and spatial location using CELESTA reveals spatial biology. Nature Methods, 19(6): 759-769. PMID: 35654951.
https://www.nature.com/articles/s41592-022-01498-z
· Bucktrout SL, Banovich NE, Butterfield LH, Cimen-Bozkus C, Giles JR, Good Z, Goodman D, Jonsson V, Laraeu C, Marson A, Maurer DM, Munson PV, Stubbington M, Taylor S, Cutchin A. (2022). Advancing T cell-based cancer therapy with single cell technologies. Nature Medicine, 28(9): 1761-1764. PMID: 36127419.
https://www.nature.com/articles/s41591-022-01986-x
· Weber EW, Lynn RC, Parker KR, Lattin J, Anbunathan H, Sotillo E, Good Z, Malipatlolla M, Xu P, Vandris P, Majzner RG, Chen L-C, Wandless TJ, Chang HY, Satpathy AT, Mackall CL. (2021). Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science, 2;372(6537): eaba1786. PMID: 33795428.
https://www.science.org/doi/10.1126/science.aba1786
· Simonetta F, Alam IS, Lohmeyer JK, Sahaf B, Good Z, Chen W, Xiao Z, Hirai T, Scheller L, Engels P, Vermesh O, Robinson E, Haywood T, Sathirachindra A, Baker J, Malipotlalla MB, Schultz LM, Spiegel JY, Lee JT, Miklos DB, Mackall CL, Gambhir SS, Negrin RS. (2021). Molecular imaging of chimeric antigen receptor T cells by ICOS-immunoPET. Clinical Cancer Research, 27(4): 1058-68. PMID: 33087332.
· Good Z, Glanville G, Gee MH, Davis MM, Khatri P. (2019). Computational and systems immunology: a students’ perspective. Trends in Immunology, 40(8): 665-8. PMID: 31288986.
https://www.sciencedirect.com/science/article/pii/S1471490619301292
· Good Z, Borges L, Vivanco Gonzalez N, Sahaf B, Samusik N, Tibshirani R, Nolan GP§, Bendall SC§. (2019). Proliferative tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells. Nature Biotechnology, 37(3): 259-66. PMID: 30742126.
https://www.nature.com/articles/s41587-019-0033-2
· Lynn RC, Weber EW, Sotillo E, Gennert D, Xu P, Good Z, Anbunathan H, Lattin J, Jones R, Tieu V, Granja J, DeBourcy C, Xu P, Majzner R, Satpathy AT, Quake SR, Chang H, Mackall CL. (2019). c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature, 576(7786): 293-300. PMID: 31802004.
https://www.nature.com/articles/s41586-019-1805-z
· Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, Leipold M, Lin DTS, Kobor MS, Horvath S. (2019). Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell, 18(6): e13028. PMID: 31496122.
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028
· Good Z*, Sarno J*, Jager A, Samusik N, Aghaeepour N, Simonds EF, While L, Lacayo NJ, Fantl WJ, Fazio G, Gaipa G, Biondi A, Tibshirani R, Bendall SC, Nolan GP§, Davis KL§. (2018). Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nature Medicine, 24(4): 474-83. PMID: 29505032.
https://www.nature.com/articles/nm.4505
· Samusik N, Good Z, Spitzer MH, Davis KL, Nolan GP. (2016). Automated mapping of phenotype space with single-cell data. Nature Methods, 13(6): 493-6. PMID: 27183440.
https://www.nature.com/articles/nmeth.3863
· Enquist IB, Good Z, Jubb AM, Fuh G, Wang X, Junttila MR, Jackson EL, Leong KG. (2014). Lymph node-independent liver metastasis in a model of metastatic colorectal cancer. Nature Communications, 5: 3530. PMID: 24667486.
https://www.nature.com/articles/ncomms4530
· Franci C, Zhou J, Jiang Z, Modrasan Z, Good Z, Jackson EL, Kouros-Mehr H. (2013). Biomarkers of residual disease, disseminated tumor cells, and metastases in the MTV-PyMT breast cancer model. PLoS ONE, 8(3): e58183. PMID: 23520493.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058183
· Dauphinee SM, Voelcker V, Tebaykina Z, Wong F, Karsan A. (2011). Heterotrimeric Gi/Go proteins modulate endothelial TLR signaling independent of the MyD88-dependent pathway. American Journal of Physiology - Heart and Circulatory Physiology, 301(6): H2246-53. PMID: 21949112.
https://journals.physiology.org/doi/full/10.1152/ajpheart.01194.2010
· Strauss DM, Lute S, Tebaykina Z, Frey DD, Ho C, Blank GS, Brorson K, Chen Q, Yang B. (2009). Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO-cell derived biotherapeutics. Biotechnology & Bioengineering, 104(2): 371-80. PMID: 19575414.
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bit.22416
*Co-first author; § co-senior author.