Research

Diagnostics & Biomarkers

By understanding the biological mechanisms underlying cancer, LSP researchers aim to improve cancer diagnosis, interception, and treatment.

To diagnose cancer, pathologists examine specimens under a microscope, using their knowledge of the morphologic and molecular features of human tissues to diagnose disease and guide treatment decisions. However, pathology is often slow to incorporate cutting-edge biological insights and methodologies into clinical practice.

The LSP brings together teams of pathologists, biologists, microscopists, and software engineers to develop new approaches to detect, diagnose, and treat disease. LSP researchers leverage novel tissue profiling and machine learning methods to understand cancer biology, from the earliest molecular changes in precursor lesions to tumor progression, metastasis, and recurrence. Such analyses hold promise for developing novel treatment approaches for a variety of lethal and treatment-resistant cancers, with the aim of progressing actionable insights into clinical trials.

Fang, R., Vallius, T., Zhang, A., Van Cura, D., Alicandri, F., Fischer, G., Draper, E., Xu, S., Pelletier, R., Wang, J., Mandinova, A., Katsyv, I., Sorger, P. K., Murphy, G. F., & Lian, C. G. (2025). PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation. Laboratory Investigation; a Journal of Technical Methods and Pathology, 104123. https://doi.org/10.1016/j.labinv.2025.104123

MacDonald, J. A., Bradshaw, G. A., Jochems, F., Bernards, R., & Letai, A. (2025). Apoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies. Cell Death and Differentiation. https://doi.org/10.1038/s41418-024-01431-1

Kader, T., Lin, J.-R., Hug, C. B., Coy, S., Chen, Y.-A., de Bruijn, I., Shih, N., Jung, E., Pelletier, R. J., Lopez Leon, M., Mingo, G., Omran, D. K., Lee, J. S., Yapp, C., Satravada, B. A., Kundra, R., Xu, Y., Chan, S., Tefft, J. B., … Santagata, S. (2024). Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-24-1366

Loi, P., Schade, A. E., Rodriguez, C. L., Krishnan, A., Perurena, N., Nguyen, V. T. M., Xu, Y., Watanabe, M., Davis, R. A., Gardner, A., Pilla, N. F., Mattioli, K., Popow, O., Gunduz, N., Lannagan, T. R. M., Fitzgerald, S., Sicinska, E. T., Lin, J.-R., Tan, W., … Cichowski, K. (2024). Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers. Cancer Discovery, 14(12), 2430–2449. https://doi.org/10.1158/2159-8290.CD-23-0866

Wala, J., de Bruijn, I., Coy, S., Gagné, A., Chan, S., Chen, Y.-A., Hoffer, J., Muhlich, J., Schultz, N., Santagata, S., & Sorger, P. K. (2024). Integrating spatial profiles and cancer genomics to identify immune-infiltrated mismatch repair proficient colorectal cancers [Preprint]. bioRxiv. https://doi.org/10.1101/2024.09.24.614701

König, L. E., Rodriguez, S., Hug, C., Daneshvari, S., Chung, A., Bradshaw, G. A., Sahin, A., Zhou, G., Eisert, R. J., Piccioni, F., Das, S., Kalocsay, M., Sokolov, A., Sorger, P., Root, D. E., & Albers, M. W. (2024). TYK2 as a novel therapeutic target in Alzheimer’s Disease with TDP-43 inclusions [Preprint]. bioRxiv. https://doi.org/10.1101/2024.06.04.595773

Coy, S., Lee, J. S., Chan, S. J., Woo, T., Jones, J., Alexandrescu, S., Wen, P. Y., Sorger, P. K., Ligon, K. L., & Santagata, S. (2024). Systematic characterization of antibody-drug conjugate targets in central nervous system tumors. Neuro-Oncology, 26(3), 458–472. https://doi.org/10.1093/neuonc/noad205

Zhou, I., Plana, D., & Palmer, A. C. (2024). Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 30(4), 786–792. https://doi.org/10.1158/1078-0432.CCR-23-0983

Rogava, M., Aprati, T. J., Chi, W.-Y., Melms, J. C., Hug, C., Davis, S. H., Earlie, E. M., Chung, C., Deshmukh, S. K., Wu, S., Sledge, G., Tang, S., Ho, P., Amin, A. D., Caprio, L., Gurjao, C., Tagore, S., Ngo, B., Lee, M. J., … Izar, B. (2024). Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation. Nature Cancer. https://doi.org/10.1038/s43018-023-00704-x

Yapp, C., Nirmal, A. J., Zhou, F. Y., Wong, A. Y. H., Tefft, J., Lu, Y. D., Shang, Z., Maliga, Z., Montero Llopis, P., Murphy, G. F., Lian, C., Danuser, G., Santagata, S., & Sorger, P. K. (2023). Highly Multiplexed 3D Profiling of Cell States and Immune Niches in Human Tumours [Preprint]. bioRxiv. https://doi.org/10.1101/2023.11.10.566670

Nirmal, A. J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A. A., Jacobson, C. A., Pelletier, R. J., Yapp, C., Arias-Camison, R., Chen, Y.-A., Lian, C. G., Murphy, G. F., Santagata, S., & Sorger, P. K. (2022). The spatial landscape of progression and immunoediting in primary melanoma at single-cell resolution. Cancer Discovery, 12(6), 1518–1541. https://doi.org/10.1158/2159-8290.CD-21-1357

Hodis, E., Torlai Triglia, E., Kwon, J. Y. H., Biancalani, T., Zakka, L. R., Parkar, S., Hütter, J.-C., Buffoni, L., Delorey, T. M., Phillips, D., Dionne, D., Nguyen, L. T., Schapiro, D., Maliga, Z., Jacobson, C. A., Hendel, A., Rozenblatt-Rosen, O., Mihm, M. C., Garraway, L. A., & Regev, A. (2022). Stepwise-edited, human melanoma models reveal mutations’ effect on tumor and microenvironment. Science (New York, N.Y.), 376(6592), eabi8175. https://doi.org/10.1126/science.abi8175

Gaglia, G., Kabraji, S., Rammos, D., Dai, Y., Verma, A., Wang, S., Mills, C. E., Chung, M., Bergholz, J. S., Coy, S., Lin, J.-R., Jeselsohn, R., Metzger, O., Winer, E. P., Dillon, D. A., Zhao, J. J., Sorger, P. K., & Santagata, S. (2022). Temporal and spatial topography of cell proliferation in cancer. Nature Cell Biology, 24(3), 316–326. https://doi.org/10.1038/s41556-022-00860-9

Hemming, M. L., Coy, S., Lin, J.-R., Andersen, J. L., Przybyl, J., Mazzola, E., Abdelhamid Ahmed, A. H., van de Rijn, M., Sorger, P. K., Armstrong, S. A., Demetri, G. D., & Santagata, S. (2021). HAND1 and BARX1 act as transcriptional and anatomic determinants of malignancy in gastrointestinal stromal tumor. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 27(6), 1706–1719. https://doi.org/10.1158/1078-0432.CCR-20-3538

Palmer, A. C., Plana, D., Gao, H., Korn, J. M., Yang, G., Green, J., Zhang, X., Velazquez, R., McLaughlin, M. E., Ruddy, D. A., Kowal, C., Muszynski, J., Bullock, C., Rivera, S., Rakiec, D. P., Elliott, G., Fordjour, P., Meyer, R., Loo, A., … Sorger, P. K. (2020). A proof of concept for biomarker-guided targeted therapy against ovarian cancer based on patient-derived tumor xenografts. Cancer Research, 80(19), 4278–4287. https://doi.org/10.1158/0008-5472.CAN-19-3850

Koch, R., Christie, A. L., Crombie, J. L., Palmer, A. C., Plana, D., Shigemori, K., Morrow, S. N., Van Scoyk, A., Wu, W., Brem, E. A., Secrist, J. P., Drew, L., Schuller, A. G., Cidado, J., Letai, A., & Weinstock, D. M. (2019). Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas. Blood, 133(6), 566–575. https://doi.org/10.1182/blood-2018-07-865527

Brastianos, P. K., Carter, S. L., Santagata, S., Cahill, D. P., Taylor-Weiner, A., Jones, R. T., Van Allen, E. M., Lawrence, M. S., Horowitz, P. M., Cibulskis, K., Ligon, K. L., Tabernero, J., Seoane, J., Martinez-Saez, E., Curry, W. T., Dunn, I. F., Paek, S. H., Park, S.-H., McKenna, A., … Hahn, W. C. (2015). Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discovery, 5(11), 1164–1177. https://doi.org/10.1158/2159-8290.CD-15-0369

Brastianos, P. K., Taylor-Weiner, A., Manley, P. E., Jones, R. T., Dias-Santagata, D., Thorner, A. R., Lawrence, M. S., Rodriguez, F. J., Bernardo, L. A., Schubert, L., Sunkavalli, A., Shillingford, N., Calicchio, M. L., Lidov, H. G. W., Taha, H., Martinez-Lage, M., Santi, M., Storm, P. B., Lee, J. Y. K., … Santagata, S. (2014). Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nature Genetics, 46(2), 161–165. https://doi.org/10.1038/ng.2868

Clark, V. E., Erson-Omay, E. Z., Serin, A., Yin, J., Cotney, J., Ozduman, K., Avşar, T., Li, J., Murray, P. B., Henegariu, O., Yilmaz, S., Günel, J. M., Carrión-Grant, G., Yilmaz, B., Grady, C., Tanrikulu, B., Bakircioğlu, M., Kaymakçalan, H., Caglayan, A. O., … Günel, M. (2013). Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science (New York, N.Y.), 339(6123), 1077–1080. https://doi.org/10.1126/science.1233009

Mendillo, M. L., Santagata, S., Koeva, M., Bell, G. W., Hu, R., Tamimi, R. M., Fraenkel, E., Ince, T. A., Whitesell, L., & Lindquist, S. (2012). HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell, 150(3), 549–562. https://doi.org/10.1016/j.cell.2012.06.031

Cho, Y.-J., Tsherniak, A., Tamayo, P., Santagata, S., Ligon, A., Greulich, H., Berhoukim, R., Amani, V., Goumnerova, L., Eberhart, C. G., Lau, C. C., Olson, J. M., Gilbertson, R. J., Gajjar, A., Delattre, O., Kool, M., Ligon, K., Meyerson, M., Mesirov, J. P., & Pomeroy, S. L. (2011). Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 29(11), 1424–1430. https://doi.org/10.1200/JCO.2010.28.5148

Dias-Santagata, D., Lam, Q., Vernovsky, K., Vena, N., Lennerz, J. K., Borger, D. R., Batchelor, T. T., Ligon, K. L., Iafrate, A. J., Ligon, A. H., Louis, D. N., & Santagata, S. (2011). BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. PloS One, 6(3), e17948. https://doi.org/10.1371/journal.pone.0017948

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Research

Diagnostics & Biomarkers

By understanding the biological mechanisms underlying cancer, LSP researchers aim to improve cancer diagnosis, interception, and treatment.

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Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers

Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma

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