Publications
Featured Publications

High-plex immunofluorescence imaging and traditional histology of the same tissue section for discovering image-based biomarkers.
Lin JR, Chen YA, Campton D, Cooper J, Coy S, Yapp C, Tefft JB, McCarty E, Ligon KL, Rodig SJ, Reese S, George T, Santagata S, Sorger PK (2023).
Nature Cancer https://doi.org/10.1038/s43018-023-00576-1
Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer.
Lin, J.-R., Wang, S., Coy, S., Tyler, M., Yapp, C., Chen, Y.-A., Heiser, C.N., Lau, K.S., Santagata, S., Sorger, P.K. (2023).
Cell, 186(19), 363-381.e19. https://doi.org/10.1016/j.cell.2022.12.028

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution.
Nirmal, A.J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A.C., Jacobson, C.A., Pelletier, R.J., ... Lian, C.G., Murphy, G.F., Santagata, S., Sorger, P.K. (2022)
Cancer Discovery, 12(6), 1518–1541. https://doi.org/10.1158/2159-8290.CD-21-1357
Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer.
Mehta, A.K., Cheney, E.M., Hartl, C.A., Pantelidou, C., Oliwa, M., Castrillon, J.A., Lin, Lin, J.-R., ... Guerriero, J. (2021).
Nature Cancer, 2(1), 66–82. https://doi.org/10.1038/s43018-020-00148-7

Temporal and spatial topography of cell proliferation in cancer.
Gaglia, G., Kabraji, S., Angyropoulu, D., Dai, Y., Wang, S., Bergholz, J., Coy, S., Lin, J.-R., ... Santagata, P. (2022).
Nature Cell Biology, 24(3), 316-326 https://doi.org/10.1038/s41556-022-00860-9
Methods and software
UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues.
Yapp, C., Novikov, E., Jang, W.-D., Chen, Y.-A., Cicconet, M., Maliga, Z., Jacobson, C. A., Wei, D., Santagata, S., Pfister, H., & Sorger, P. K. (2022).
Nature Communications Biology https://doi.org/10.1038/s42003-022-04076-3
Stitching and registering highly multiplexed whole-slide images of tissues and tumors using ASHLAR.
Muhlich, J., Chen, Y.-A., Yapp, C., Russell, R., Santagata, S., & Sorger, P.K. (2022).
Bioinformatics, btac544 https://doi.org/10.1093/bioinformatics/btac544
Narrative online guides for the interpretation of digital-pathology images and tissue-atlas data.
Rumana, R., Chen, Y.-A., Hoffer, J., Muhlich, J.L., Lin, J.-R., Krueger, R., Pfister, H., Mitchell, R., Santagata, S., & Sorger, P. K. (2022).
Nature Biomedical Engineering, 6(5):515-526. https://pubmed.ncbi.nlm.nih.gov/34750536/
Scope2Screen: Focus+context techniques for pathology tumor assessment in multivariate image data.
Jessup, J., Krueger, R., Warchol, S., Hoffer. J., Muhlich, J.L., Ritch, C.C., Gaglia, G., Coy, S., Chen Y.-A., Lin J-.R., Santagata, S., Sorger, P.K., & Pfister, H. (2022).
IEEE Transactions on Visualization and Computer Graphics, 28(1), 259-269. https://pubmed.ncbi.nlm.nih.gov/34606456/
MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging.
Schapiro, D., Sokolov, A., Yapp, C., Muhlich, J.L., Hess, J., Lin, J-R., Chen, Y-A., Nariya, M.K., ... Sorger, P.K. (2021)
Nature Methods, 19, 311–315 https://doi.org/10.1038/s41592-021-01308-y
MITI minimum information guidelines for highly multiplexed tissue images.
Schapiro, D., Yapp, C., Sokolov, A., Reynolds, S.M., Chen, Y.-A., Sudar, D., Xie, Y., Muhlich, J., ... Sorger, P.K. (2022).
Nature Methods, 19, 262–267 https://doi.org/10.1038/s41592-022-01415-4
Micro-region transcriptomics of fixed human tissue using pick-seq.
Maliga, Z., Nirmal, A. J., Ericson, N. G., Boswell, S. A., U’Ren, L., Podyminogin, R., Chow, J., Chen, Y.-A., … Sorger, P. K. (2021).
Channel embedding for informative protein identification from highly multiplexed images.
Magid, S.M., Jang, W.-D., Schapiro, D., Wei, D., Tompkin, J., Sorger, P.K., & Pfister, H. (2020).
Medical Image Computing and Computer-Assisted Intervention (MICCAI), 12265, 3–13. https://doi.org/10.1007/978-3-030-59722-1_1
Multiplexed proteomics and imaging of resolving and lethal SARS-CoV-2 infection in the lung.
Kalocsay, M., Maliga, Z., Nirmal, A.J., Eisert, R.J., Bradshaw, G.A., Solomon, I. H., Chen, Y-A., Pelletier, R.J., ... Sorger, P.K. (2020).
Minerva: A light-weight, narrative image browser for multiplexed tissue images.
Hoffer, J., Rashid, R., Muhlich, J.L., Chen, Y.-A., Russell, D.P.W., Ruokonen, J., Krueger, R., Pfister, H., Santagata, S., & Sorger, P.K. (2020).
Journal of Open Source Software, 5(54), 2579 https://doi.org/10.21105/joss.02579

Facetto: Combining Unsupervised and Supervised Learning for Hierarchical Phenotype Analysis in Multi-Channel Image Data.
Krueger, R., Beyer, J., Jang, W.-D., Kim, N. W., Sokolov, A., Sorger, P. K., & Pfister, H. (2020).
IEEE Transactions on Visualization and Computer Graphics, 26(1), 227–237. https://doi.org/10.1109/TVCG.2019.2934547

Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging.
Du, Z., Lin, J.-R., Rashid, R., Maliga, Z., Wang, S., Aster, J. C., Izar, B., Sorger, P. K., & Santagata, S. (2019).
Nature Protocols, 14(10), 2900–2930. https://doi.org/10.1038/s41596-019-0206-y

Highly multiplexed immunofluorescence images and single-cell data of immune markers in tonsil and lung cancer.
Rashid, R., Gaglia, G., Chen, Y.-A., Lin, J.-R., Du, Z., Maliga, Z., Schapiro, D., Yapp, C., Muhlich, J., Sokolov, A., Sorger, P., & Santagata, S. (2019).
Scientific Data, 6(1), 323. https://doi.org/10.1038/s41597-019-0332-y
Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-cycif and conventional optical microscopes.
Lin, J.-R., Izar, B., Wang, S., Yapp, C., Mei S., Shah, P.M., Santagata, S., & Sorger, P.K. (2018).
ELife, 7. https://doi.org/10.7554/eLife.31657
Profiling and Atlasing

Spatial intra-tumor heterogeneity is associated with survival of lung adenocarcinoma patients.
Wu, H.-J., Temko, D., Maliga, M., Moreira. A., Sei, E., Conterno Minussi, D., Dean, J., Lee, C. Xu, Q., ... Michor, F. (2022).
Cell Genomics, 2(8), 100165. https://doi.org/10.1016/j.xgen.2022.100165

A human breast atlas integrating single-cell proteomics and transcriptomics.
Gray, G.K., Li, C.M.-C., Rosenbluth, J.M., Selfors, L.M., Girnius, N., Lin, J.-R., Schackmann, R.C.J., Goh, W.L., Moore, K., Shapiro, H.K., Mei, S., D’Andrea, K., Nathanson, K.L., Sorger, P.K., Santagata, S., Regev, A., Garber, J.E., Dillon, D.A., Brugge, J.S. (2022).
Developmental Cell, 57(22), 1400-1420. https://doi.org/10.1016/j.devcel.2022.05.003

The immunoregulatory landscape of human tuberculosis granulomas.
McCaffrey EF, Donato M, Keren L, Chen Z, Delmastro A, Fitzpatrick MB, Gupta S, Greenwald NF,... Angelo M. (2022).
Nature Immunology, 23(2):318–329. https://doi.org/10.1038/s41590-021-01121-x
Evolution of delayed resistance to immunotherapy in a melanoma responder.
Liu, D., Lin, J.-R., Robitschek, E.J., Kasumova, G.G., Heyde, A., Shi, A., Kraya, A., ... Boland, G.M. (2021).
Nature Medicine, 27, 985–992. https://doi.org/10.1038/s41591-021-01331-8
Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma.
Jerby-Arnon, L., Neftel, C., Shore, M. E., Weisman, H. R., Mathewson, N. D., McBride, M. J., Haas, B., Izar, B., … Regev, A. (2021).
Nature Medicine, 27(2), 289–300. https://doi.org/10.1038/s41591-020-01212-6
Clinical efficacy and molecular response correlates of the WEE1 inhibitor adavosertib combined with cisplatin in patients with metastatic triple-negative breast cancer.
Keenan, T.E., Li, T., Vallius, T., Guerriero, J.L., Tayob, N., Kochupurakkal, B., Davis, J., Pastorello, R., ... Tolaney, S.M. (2021).
Clinical Cancer Research, 2(1), 66-82. https://doi.org/10.1158/1078-0432.CCR-20-3089
HAND1 and BARX1 act as transcriptional and anatomic determinants of malignancy in gastrointestinal stromal tumor.
Hemming, M.L., Coy, S., Lin, J.-R., Andersen, J.L., Przybyl, J., Mazzola, E., Abdelhamid Ahmed, A.H., ... Santagata, S. (2021).
Clinical Cancer Research, 27(6), 1706-19. https://doi.org/10.1158/1078-0432.CCR-20-3538
Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma.
Iorgulescu, J.B., Gokhale, P.C., Speranza, M.C., Eschle, B.K., Poitras, M.J., Wilkens, M.K., Soroko, K.M., ... Reardon, D.A. (2021).
Clinical Cancer Research, 27(1), 276–87. https://doi.org/10.1158/1078-0432.CCR-20-2291
Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity.
Ringel, A.E., Drijvers, J.M., Baker, G.J., Catozzi, A., García-Cañaveras, J.C., Gassaway, B.M., Miller, B.C., ... Haigis, M.C. (2020).
Cell, 183(7), 1848-1866.e26. https://doi.org/10.1016/j.cell.2020.11.009
SARS-CoV-2 infection protects against rechallenge in rhesus macaques.
Chandrashekar, A., Liu, J., Martinot, A.J., McMahan, K., Mercado, N.B., Peter, L., Tostanoski, L.H., ... Barach, D.H. (2020).
Science 369(6505): 812–17. https://doi.org/10.1126/science.abc4776

Response and mechanisms of resistance to larotrectinib and selitrectinib in metastatic undifferentiated sarcoma harboring oncogenic fusion of NTRK1.
Hemming, M. L., Nathenson, M. J., Lin, J.-R., Mei, S., Du, Z., Malik, K., Marino-Enriquez, A., Jagannathan, J. P., Sorger, P. K., Bertagnolli, M., Sicinska, E., Demetri, G. D., & Santagata, S. (2020).
JCO Precision Oncology, 4, 79–90. https://doi.org/10.1200/po.19.00287

Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer.
Färkkilä, A., Gulhan, D. C., Casado, J., Jacobson, C. A., Nguyen, H., Kochupurakkal, B., Maliga, Z., Yapp, C., … Konstantinopoulos, P. A. (2020).
Nature Communications, 11(1), 1459. https://doi.org/10.1038/s41467-020-15315-8

HSF1 phase transition mediates stress adaptation and cell fate decisions.
Gaglia, G., Rashid, R., Yapp, C., Joshi, G. N., Li, C. G., Lindquist, S. L., Sarosiek, K. A., Whitesell, L., Sorger, P. K., & Santagata, S. (2020).
Nature Cell Biology, 22(2), 151–158. https://doi.org/10.1038/s41556-019-0458-3

Mismatch repair deficiency in high-grade meningioma: A rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade.
Dunn, I. F., Du, Z., Touat, M., Sisti, M. B., Wen, P. Y., Umeton, R., Dubuc, A. M., Ducar, M., ... & Reardon, D.A. (2018).
JCO Precision Oncology, 2018. https://doi.org/10.1200/PO.18.00190
Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma.
Coy, S., Rashid, R., Lin, J.R., Du, Z., Donson, A.M., Hankinson, T.C., Foreman, N.K., ... Santagata, S. (2018).
Neuro-Oncology, 20(8), 1101-12. https://doi.org/10.1093/neuonc/noy035

A cancer cell program promotes t cell exclusion and resistance to checkpoint blockade.
Jerby-Arnon, L., Shah, P., Cuoco, M. S., Rodman, C., Su, M.-J., Melms, J. C., Leeson, R., Kanodia, A., … Regev, A. (2018).
Cell, 175(4), 984-997.e24. https://doi.org/10.1016/j.cell.2018.09.006

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., … Garraway, L. A. (2016).
Science, 352(6282), 189–196. https://doi.org/10.1126/science.aad0501