Marie Webster

About

• 2019–present: Assistant Professor, LIMR
• 2019–present: Affiliate Member, Wistar Institute Cancer Center, Philadelphia
• 2020–present: Associate Member, Cancer Cell Biology and Signaling program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia
• 2016–2019: Staff Scientist, Wistar Institute

Research descriptions

The Webster lab is interested in delineating the underlying mechanisms of phenotype plasticity that lead to therapy resistance and disease progression in melanoma. Current projects in the lab include investigating the role of Wnt signaling and slow cycling cells in melanoma progression and epigenetic changes that occur in highly metastatic cells that promote survival following multiple types of stress.

Metastatic melanoma is highly therapy resistant. Patients who receive targeted therapy and chemotherapy often relapse due to the emergence of resistant populations. Resistant populations, which emerge following several types of stress, exhibit characteristics of a more invasive phenotype. We have observed that highly invasive melanoma cells undergo a senescent-like adaptive response following multiple types of stress. This response includes cell cycle arrest, beta-gal positivity, increased PML bodies, increased heterochromatic foci, increase in histone methylation as well as senescence associated secretory phenotype (SASP; Webster et al., PMCR). However, these cells are highly invasive and retain clonogenic properties. Understanding the mechanisms that allow these cells to survive, invade and proliferate may lead to new therapeutic strategies.

Publications

• Progress in melanoma treatment: Patient's perspectives. Alicea GM, Villanueva J, Webster MR, et al. Pigment Cell Melanoma Res. 2023 Oct 11. doi: 10.1111/pcmr.13138.
• Next-generation of melanoma researchers: Trainee perspectives from around the world. Webster MR, Brathwaite R, et al. Pigment Cell Melanoma Res. 2023 Oct 11. doi: 10.1111/pcmr.13136.
• Stromal changes in the aged lung induce an emergence from melanoma dormancy. Fane ME, Chhabra Y, … Webster MR, et al. Nature. 2022 Jun 1. https://doi.org/10.1038/s41586-022-04774-2
• sFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients. Fane ME, Ecker BL, Kaur A, Webster MR, et al. Clin Cancer Res. 2020 Oct 23. doi: 10.1158/1078-0432.CCR-20-0446.
• Stromal changes in the aged lung induce an emergence from melanoma dormancy. Weeraratna A, Fane M, Douglass S, … Webster M, et al. Nature Research. 2020 Sept. doi: 10.21203/rs.3.rs-61165/v1.
• Changes in Aged Fibroblast Lipid Metabolism Induce Age-dependent Melanoma Cell Resistance to Targeted Therapy Via the Fatty Acid Transporter FATP2. Alicea GM, Rebecca VW, Goldman AR … Webster MR, et al. Cancer Discov 2020 Jun 4;CD-20-0329.
• Paradoxical Role for Wild-Type p53 in Driving Therapy Resistance in Melanoma. Webster MR, Fane ME, Alicea GM, et al. Mol Cell. 2020;77(3):633-644.e5.
• Age-related changes in HAPLN1 increases lymphatic permeability and affect routes of melanoma metastasis. Ecker B, Kaur A, Douglass SM, Webster MR, et al. Cancer Discov, 2019;9(1):82-95.
• Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and affects immune cell motility. Kaur A, Ecker B, Douglass SM, Kugel III CH, Webster MR, et al. Cancer Discov, 2019;9(1):64-81.
• Age correlates with response to Anti-PD- 1, reflecting age-related differences in intratumoral effector and regulatory T-Cell populations. Kugel III CH, Douglass SM, Webster MR, et al. Clin Cancer Res, 2018;24(21):5347-56.
• sFRP2 in the aged microenvironment drives metastasis and resistance to targeted therapy. Kaur A, Webster MR, Marchbank K, et al. Nature 2016;532(7598):250-4.
• Wnt5A promotes an adaptive senescent-like stress response, while continuing to drive invasion in melanoma cells. Webster MR, Xu M, et al. Pigment Cell Melanoma Res 2015;28(2):184-95.