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. ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma
  2. The Autophagy Receptor Adaptor p62 is Up-regulated by UVA Radiation in Melanocytes and in Melanoma Cells
  3. In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms
  4. A preexisting rare PIK3CAe545ksubpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling
  5. Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma
  6. Novel therapeutic strategies and targets in advanced uveal melanoma
  7. CKS1 expression in melanocytic nevi and melanoma
  8. Response and resistance to paradox-breaking BRAF inhibitor in melanomas in vivo and Ex vivo
  9. A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma
  10. “If you want to go far, go together”
  11. Establishment of an orthotopic patient-derived xenograft mouse model using uveal melanoma hepatic metastasis
  12. Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of klotho
  13. Dysregulated GPCR signaling and therapeutic options in uveal melanoma
  14. Co-Targeting HGF/cMET Signaling with MEK Inhibitors in metastatic uveal melanoma
  15. Running INTERFERONce on immunotherapy
  16. An in vivo reporter to quantitatively and temporally analyze the effects of CDK4/6 inhibitor-based therapies in melanoma
  17. Triple jeopardy for people with albinism
  18. The melanoma field with dendritic roots
  19. The state of melanoma: challenges and opportunities
  20. Targeting mutant NRAS signaling pathways in melanoma