Our work in melanoma integrates current knowledge of genomic drivers with studies of the small GTPase ARF6, which controls critical cellular functions such as vesicular trafficking, cytoskeletal rearrangements, cell-cell adhesive interactions, motility, invadopodia, tumor microvesicle shedding and exosome generation. Through our studies of ARF6, we hope to illuminate how small GTPases potentiate signaling from classic oncogenic pathways such as WNT/b-catenin, RAS, BRAF/MAPK, and PI3K/AKT. In addition, we are probing the role of ARF6 in the tumor inflammatory microenvironment, as ARF6 is known to be critical for inflammatory cytokine signaling leading to vascular leak, edema, and end-organ damage in sepsis, arthritis, and retinopathy. Tumor-intrinsic inflammatory signaling has been linked to cancer progression and may represent a mechanism by which ARF6 promotes tumor growth, invasion, metastasis and perhaps tumor immune evasion.
We use a variety of in vitro and in vivo approaches to study cancer progression, including genetically-engineered mouse models, xenografts, cell culture, microscopy, biochemical, molecular biological, and genomic approaches. With clinical expertise in Anatomic and Molecular Pathology, trainees have access to mentored skill development by Dr. Grossmann in gross and microscopic morphologic assessment of in vivo tumor model systems.
View our recent article about melanoma spreading without tumor growth.