Vito Rebecca Lab
Studying acral lentiginous melanoma metastasis and therapy escape to develop therapies that increase cancer curability
About the Rebecca Lab
Why do some cancers respond better to a given drug or metastasize to a greater extent than others? How does race/ethnicity influence these differences? How does the intracellular “nature” of certain cancers and the “nurturing” microenvironment surrounding the cancer cells affect how aggressive they become? The Rebecca Lab is intrigued by these nature versus nurture nuances that may profoundly dictate why certain subtypes of melanoma are much more lethal than others across different patient populations. The Rebecca Lab uses systems biology, biochemical, advanced microscopy, and in vivo tools to explore these open questions.
We are a culturally and intellectually diverse group who come to the lab from different life experiences. We are biochemists and mouse model developers who collaborate with bioengineers, mathematicians, clinicians, and synthetic biologists throughout the world to develop improved treatment strategies for metastatic melanoma.
Research Overview
The Rebecca Lab focuses on understanding the mechanisms leveraged by tumor cell subpopulations that metastasize and escape targeted- and immunotherapy, using acral lentiginous melanoma as a paradigm. ALM is a unique melanoma subtype that most frequently arises on the palms, fingernail beds, and the sole of feet. Our studies use quantitative tools, genetic editing, molecular biology, in vivo patient-derived xenograft therapy trials, and bioinformatic analyses to arrive at a comprehensive understanding of actionable vulnerabilities to address therapy resistance and metastasis for patients with AM. Our interests include autophagy-lysosome activity, MAPK and PI3K signaling plasticity, and the tumor immune microenvironment. By focusing on a cancer with persisting racial disparities, we hope to develop strategies that bring therapeutic benefit to the entire patient population.
ALM and Resistance
About 60% of ALM patients have CDK4/6 gene mutations, but a recent CDK4/6 inhibitor clinical trial showed limited improvements and suggested that the cancer developed resistance. Led by senior research scientist Kasturee Jagirdar, the Rebecca Lab identified two resistance mechanisms: hyperactivation of MAPK signaling, which drove upregulation of Cyclin D1. Pairing the CDK4/6 inhibitor with a MAPK pathway inhibitor was more effective than either drug alone.
Also, CDK4/6 protein expression in ALM cells correlated poorly with predictions based on the genetic mutations, suggesting that ALM patients may need protein expression testing, not just tumor sequencing, to evaluate the likely benefits from CDK4/6 inhibitors.
ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma, Jagirdar K, et al., Oncogene, 2023.
Selected Publications
Robertson BM, Fane ME, Weeraratna AT, Rebecca VW. Determinants of resistance and response to melanoma therapy. Nature Cancer, 2024.
Jagirdar K, Portuallo ME, Wei M, Wilhide M, Bravo Narula JA, Robertson BM, Alicea GM, Aguh C, Xiao M, Godok T, Fingerman D, Brown GS, Herlyn M, Elad VM, Guo X, Toska E, Zabransky DJ, Wubbenhorst B, Nathanson KL, Kwatra S, Goyal Y, Ji H, Liu Q, Rebecca VW. ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma. Oncogene, 2024.
Alicea GM, Rebecca VW. Emerging strategies to treat rare and intractable subtypes of melanoma. Pigment Cell & Melanoma Research, 2020.
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.
Rebecca VW, Nicastri MC, Fennelly C, Chude CI, Barber-Rotenberg JS, Ronghe A, McAfee Q, McLaughlin NP, Martorella A, Alicea GM, Lee JJ, Schuchter LM, Xu X, Herlyn M, Marmorstein R, Gimotty PA, Speicher DW, Winkler JD, Amaravadi RK. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discovery, 2019.
How to Join the Rebecca lab
Rebecca Lab members join us from many pathways. Common ways to join the Lab are below.
PhD Students
The Rebecca Lab is part of the Biochemistry and Molecular Biology PhD training program in the Johns Hopkins Bloomberg School of Public Health and the Cellular and Molecular Medicine Program in the Johns Hopkins School of Medicine. Visit the websites to learn more about the programs and how to apply.
Master's Students
The Rebecca Lab takes students from the Department of Biochemistry and Molecular Biology Master of Health Science and Master of Science programs.
Postdoctoral Fellows
To apply to be a postdoctoral fellow in the Rebecca Lab, send an email to Vito Rebecca with a CV and statement of interest. In addition to training within our lab, the Biochemistry and Molecular Biology Department has an active postdoctoral training program.