The Center for Cancer Systems Pharmacology

Research

Inflammation in Disease

LSP investigators study the causes and consequences of inflammation in various diseases.

Inflammation is a tightly regulated biological response that orchestrates the recruitment of immune and stromal cells to sites of injury or infection. Under normal conditions, the inflammatory response is short-lived and resolves once the insult has been cleared. However, if the inflammation fails to resolve appropriately, it can become chronic and contribute to a range of diseases. While the role of inflammation in autoimmune conditions is well-understood, low-grade chronic inflammation also plays a role in cancer, neurodegenerative diseases, and chronic pain.

Investigators at the LSP use preclinical methods to understand the spatial and temporal dynamics of inflammation in disease. Recent work has used spatial imaging and transcriptomics to reveal the complex immune dysregulation in ovarian precancer, identified a potential pro-inflammatory biomarker for neuroinflammation, and linked unique inflammatory profiles to different types of pain. These studies aim to define disease-specific inflammatory signatures, enabling targeted therapies to modulate pathological inflammation without broadly suppressing immune function. 

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June 5, 2024
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Featured Publications

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

Kader et al.
Cancer Discovery. 2025 May 5. PMID: 39704522.
Journal
PubMed

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain

Jain et al.
Nat Immunol. 2024 May 28. PMCID: PMC11224023
Journal
PubMed

Related Publications

Jain, N., Ogbonna, E. C., Maliga, Z., Jacobson, C., Zhang, L., Shih, A., Rosenberg, J., Kalam, H., Gagné, A., Solomon, I. H., Santagata, S., Sorger, P. K., Aldridge, B. B., & Martinot, A. J. (2025). Multiomic analysis identifies suppressive myeloid cell populations in human TB granulomas [Preprint]. bioRxiv. https://doi.org/10.1101/2025.03.10.642376
Mollaoglu, G., Tepper, A., Falcomatà, C., Potak, H. T., Pia, L., Amabile, A., Mateus-Tique, J., Rabinovich, N., Park, M. D., LaMarche, N. M., Brody, R., Browning, L., Lin, J.-R., Zamarin, D., Sorger, P. K., Santagata, S., Merad, M., Baccarini, A., & Brown, B. D. (2024). Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell, 187(26), 7492-7510.e22. https://doi.org/10.1016/j.cell.2024.10.006
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
Yu, W.-W., Barrett, J. N. P., Tong, J., Lin, M.-J., Marohn, M., Devlin, J. C., Herrera, A., Remark, J., Levine, J., Liu, P.-K., Fang, V., Zellmer, A. M., Oldridge, D. A., Wherry, E. J., Lin, J.-R., Chen, J.-Y., Sorger, P., Santagata, S., Krueger, J. G., … Lu, C. P. (2024). Skin immune-mesenchymal interplay within tertiary lymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa. Immunity, 57(12), 2827-2842.e5. https://doi.org/10.1016/j.immuni.2024.11.010
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Park, J. H., Mortaja, M., Son, H. G., Zhao, X., Sloat, L. M., Azin, M., Wang, J., Collier, M. R., Tummala, K. S., Mandinova, A., Bardeesy, N., Semenov, Y. R., Mino-Kenudson, M., & Demehri, S. (2024). Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression. Nature Communications, 15(1), 4099. https://doi.org/10.1038/s41467-024-48441-8
Jain, A., Gyori, B. M., Hakim, S., Jain, A., Sun, L., Petrova, V., Bhuiyan, S. A., Zhen, S., Wang, Q., Kawaguchi, R., Bunga, S., Taub, D. G., Ruiz-Cantero, M. C., Tong-Li, C., Andrews, N., Kotoda, M., Renthal, W., Sorger, P. K., & Woolf, C. J. (2024). Nociceptor-immune interactomes reveal insult-specific immune signatures of pain. Nature Immunology. https://doi.org/10.1038/s41590-024-01857-2
Marques, C., Held, A., Dorfman, K., Sung, J., Song, C., Kavuturu, A. S., Aguilar, C., Russo, T., Oakley, D. H., Albers, M. W., Hyman, B. T., Petrucelli, L., Lagier-Tourenne, C., & Wainger, B. J. (2024). Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathologica, 147(1), 56. https://doi.org/10.1007/s00401-024-02688-z
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
Coy, S., Cheng, B., Lee, J. S., Rashid, R., Browning, L., Xu, Y., Chakrabarty, S. S., Yapp, C., Chan, S., Tefft, J. B., Scott, E., Spektor, A., Ligon, K. L., Baker, G. J., Pellman, D., Sorger, P. K., & Santagata, S. (2023). 2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer [Preprint]. bioRxiv. https://doi.org/10.1101/2023.11.07.566063
Bang, S., Shin, Y.-H., Ma, X., Park, S.-M., Graham, D. B., Xavier, R. J., & Clardy, J. (2023). A Cardiolipin from Muribaculum intestinale Induces Antigen-Specific Cytokine Responses. Journal of the American Chemical Society, 145(43), 23422–23426. https://doi.org/10.1021/jacs.3c09734
Wang, H., Wang, Y., Li, J., He, Z., Boswell, S. A., Chung, M., You, F., & Han, S. (2023). Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes. BMC Medicine, 21(1), 147. https://doi.org/10.1186/s12916-023-02838-2
Ding, L., Wang, Q., Martincuks, A., Kearns, M. J., Jiang, T., Lin, Z., Cheng, X., Qian, C., Xie, S., Kim, H.-J., Launonen, I.-M., Färkkilä, A., Roberts, T. M., Freeman, G. J., Liu, J. F., Konstantinopoulos, P. A., Matulonis, U., Yu, H., & Zhao, J. J. (2023). STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer. Journal for Immunotherapy of Cancer, 11(1), e005627. https://doi.org/10.1136/jitc-2022-005627
Coy, S., Wang, S., Stopka, S. A., Lin, J.-R., Yapp, C., Ritch, C. C., Salhi, L., Baker, G. J., Rashid, R., Baquer, G., Regan, M., Khadka, P., Cole, K. A., Hwang, J., Wen, P. Y., Bandopadhayay, P., Santi, M., De Raedt, T., Ligon, K. L., … Santagata, S. (2022). Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma. Nature Communications, 13(1), 4814. https://doi.org/10.1038/s41467-022-32430-w
Wang, Q., Bergholz, J. S., Ding, L., Lin, Z., Kabraji, S. K., Hughes, M. E., He, X., Xie, S., Jiang, T., Wang, W., Zoeller, J. J., Kim, H.-J., Roberts, T. M., Konstantinopoulos, P. A., Matulonis, U. A., Dillon, D. A., Winer, E. P., Lin, N. U., & Zhao, J. J. (2022). STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer. Nature Communications, 13(1), 3022. https://doi.org/10.1038/s41467-022-30568-1
Rodriguez, S., Sahin, A., Schrank, B. R., Al-Lawati, H., Costantino, I., Benz, E., Fard, D., Albers, A. D., Cao, L., Gomez, A. C., Evans, K., Ratti, E., Cudkowicz, M., Frosch, M. P., Talkowski, M., Sorger, P. K., Hyman, B. T., & Albers, M. W. (2021). Genome-encoded cytoplasmic double-stranded RNAs, found in C9ORF72 ALS-FTD brain, propagate neuronal loss. Science Translational Medicine, 13(601), eaaz4699. https://doi.org/10.1126/scitranslmed.aaz4699
Mills, E. L., Harmon, C., Jedrychowski, M. P., Xiao, H., Garrity, R., Tran, N. V., Bradshaw, G. A., Fu, A., Szpyt, J., Reddy, A., Prendeville, H., Danial, N. N., Gygi, S. P., Lynch, L., & Chouchani, E. T. (2021). UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nature Metabolism, 3(5), 604–617. https://doi.org/10.1038/s42255-021-00389-5
Rodriguez, S., Cao, L., Rickenbacher, G. T., Benz, E. G., Magdamo, C., Gomez, L. R., Holbrook, E. H., Albers, A. D., Gallagher, R., Westover, M. B., Evans, K. E., Tatar, D. J., Mukerji, S., Zafonte, R., Boyer, E. W., Yu, C. R., & Albers, M. W. (2020). Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients [Preprint]. medRxiv. https://doi.org/10.1101/2020.06.14.20131128
Melms, J. C., Vallabhaneni, S., Mills, C. E., Yapp, C., Chen, J.-Y., Morelli, E., Waszyk, P., Kumar, S., Deming, D., Moret, N., Rodriguez, S., Subramanian, K., Rogava, M., Cartwright, A. N. R., Luoma, A., Mei, S., Brinker, T. J., Miller, D. M., Spektor, A., … Izar, B. (2020). Inhibition of haspin kinase promotes cell-intrinsic and extrinsic antitumor activity. Cancer Research, 80(4), 798–810. https://doi.org/10.1158/0008-5472.CAN-19-2330

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