Ashi Weeraratna, PhD, studies how cancer cells move to distant sites and how changes in the normal cells around a tumor contribute to their movement, especially as we age.
Cancer; Aging; Metastasis; Melanoma; Matrix; Wnt; Wnt5A
Experiences & Accomplishments
Dr. Weeraratna is an expert in melanoma metastasis, Wnt signaling, and aging, and her research focuses heavily on the effects of the tumor microenvironment on metastasis and therapy resistance. Beyond the lab she is a member of the National Cancer Advisory Board, advocates for early career researchers and the importance of a diverse scientific enterprise, and promotes skin safety practices from sunscreen use to avoiding tanning beds.
Dr. Weeraratna was one of the first to study how the aging microenvironment guides metastasis and therapy resistance in melanoma. Her studies encompass biophysical changes that affect the ability of both tumor and immune cells to migrate, that affect vasculature integrity thus dictating routes of metastasis, and also secreted changes that drive metastatic signaling and response to therapy. The Weeraratna laboratory has also undertaken a global analysis of how the aged microenvironment promotes metastasis, using a unique resource of normal skin fibroblasts from healthy donors of differing ages, proteomics analysis, and animal models. The implications of these data may also result in a change in clinical practice, as her lab is finding age-related differences in responses to both targeted and immunotherapy. Dr. Weeraratna is using these proteomics data to guide further studies on how the aging microenvironment affects tumor dormancy and cellular metabolism.
Fane ME, Chhabra Y, Alicea GM, Maranto DA, Douglass SM, Webster MR, Rebecca VW, Marino GE, Almeida F, Ecker BL, Zabransky DJ, Hüser L , Beer, T, Tang H-Y, Kossenkov A, Herlyn M, Speicher DW, Xu W, Xu X, Jaffee EM, Aguirre-Ghiso JA, & Weeraratna AT. Stromal Changes in The Aged Lung Induce an Emergence From Melanoma Dormancy. Nature, 2022 Jun 1;605(7910)
Douglass SM, Fane ME, Sanseviero E, Ecker BL, Kugel CH 3rd, Behera R, Kumar V, Tcyganov EN, Yin X, Liu Q, Chhabra Y, Alicea GM, Kuruvilla R, Gabrilovich DI, Weeraratna AT. Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity. Cancer Research, 2021 Feb 1;81(3):658-670.
Fane ME, Ecker BL, Kaur A, Marino GE, Alicea GM, Douglass SM, Chhabra Y, Webster MR, Marshall A, Colling R, Espinosa O, Coupe N, Maroo N, Campo L, Middleton MR, Corrie P, Xu X, Karakousis GC, Weeraratna AT. sFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients. Clin Cancer Res. 2020 Nov 1;26(21):5709-5719.
Alicea GM, Rebecca VW, Goldman AR, Fane ME, Douglass SM, Behera R, Webster MR, Kugel CH, Ecker BL, Caino MC, Kossenkov AV, Tang HY, Frederick DT, Flaherty KT, Xu X, Liu Q, Gabrilovich DI, Herlyn M, Blair IA, Schug ZT, Speicher DW, Weeraratna AT. Changes in Aged Fibroblast Lipid Metabolism Induce Age-dependent Melanoma Cell Resistance to Targeted Therapy Via the Fatty Acid Transporter FATP2. Cancer Discovery. 2020 Jun 4:CD-20-0329.
Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nat Rev Cancer. 2020;20(2):89-106.