Philadelphia University + Thomas Jefferson University
Sidney Kimmel Medical College
Department of Dermatology & Cutaneous Biology

Aplin, Andrew

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Aplin

Andrew E. Aplin, PhD

Contact Dr. Aplin

Bluemle Life Sciences Building, Room 522
233 South Tenth Street
Philadelphia, PA 19107

(215) 503-7296
(215) 923-9248 fax

Research and Clinical Interests

Melanoma arises from epidermal melanocytes, the pigment producing cells in the skin, or their progenitors. Currently, melanoma metastasis is only preventable by early detection and surgical excision of primary tumors; hence, there is an immediate need to understand the mechanisms underlying melanocyte transformation. We utilize molecular and clinical grade inhibitor approaches to alter key signaling pathway in primary human melanocytes and a panel of melanoma cells characterizing different stages of melanoma progression. We test the role of target proteins in 3D skin mimetic in vitro systems and an intradermal in vivo imaging model.

The serine/threonine kinase, B-RAF, is somatically mutated in ~60% of melanomas. Mutant B-RAF hyper-activates signaling, which is required for melanoma growth and invasion. One focus in the laboratory is determining the effectors of mutant B-RAF signaling that elicit malignant traits in melanoma cells. We have shown a role for Bcl-2 family proteins and integrin-mediated adhesion in the survival properties of melanoma cells, and a function for the GTPase, Rnd3, in cell invasion and migration in 3D. Recently, we have identified a stemness factor, FOXD3, which is up-regulated in mutant B-RAF melanoma cells following targeting of the mutant B-RAF signaling pathway. We are currently investigating the role of up-regulated FOXD3 in melanoma. Ultimately, we expect to identify the mechanisms underlying invasive growth of melanomas and, in doing so, identify novel targets for therapeutic intervention.

Clinical trials utilizing RAF inhibitors in late-stage mutant B-RAF melanoma patients are underway. The majority of patients enrolled in a recent RAF inhibitor trials showed dramatic clinical responses. Unfortunately, most of the original responders are now eliciting drug resistance. This acquired/secondary resistance is a major obstacle to the prolonged effects of kinase inhibitor therapies. We are elucidating modes of resistance to RAF inhibitors with the view that identifying novel RAF inhibitor resistance mechanisms will direct new combinatorial trials for melanoma.

Publications

Most Recent Peer-Reviewed Publications

  1. Establishment of an orthotopic patient-derived xenograft mouse model using uveal melanoma hepatic metastasis
  2. Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of klotho
  3. Dysregulated GPCR signaling and therapeutic options in uveal melanoma
  4. Co-Targeting HGF/cMET Signaling with MEK Inhibitors in metastatic uveal melanoma
  5. The Autophagy Receptor Adaptor p62 is Up-regulated by UVA Radiation in Melanocytes and in Melanoma Cells
  6. An in vivo reporter to quantitatively and temporally analyze the effects of CDK4/6 inhibitor-based therapies in melanoma
  7. Triple jeopardy for people with albinism
  8. The melanoma field with dendritic roots
  9. The state of melanoma: challenges and opportunities
  10. Targeting mutant NRAS signaling pathways in melanoma
  11. Of Mice and melanoma: PDX system for modeling personalized medicine
  12. Welcome to the New Year!
  13. MIG6 Is MEK Regulated and Affects EGF-Induced Migration in Mutant NRASĀ Melanoma
  14. Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization
  15. The Broad Stroke of Hsp90 Inhibitors: Painting over the RAF Inhibitor Paradox
  16. Fibroblast-derived neuregulin 1 promotes Compensatory ErbB3 receptor signaling in mutant BRAF melanoma
  17. PAX3 and FOXD3 promote CXCR4 expression in melanoma
  18. RAC1 P29S regulates PD-L1 expression in melanoma
  19. ErbB3-ErbB2 complexes as a therapeutic target in a subset of wild-type BRAF/NRAS cutaneous melanomas
  20. Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer