Research in the Aplin laboratory focuses on melanoma, a type of cancer which arises from the transformation of melanocytes. The incidence rate of melanoma is rising and despite recent therapeutic advances, many patients do not respond to therapies or eventually relapse despite continued treatment. Therefore, understanding how melanomas adapt and develop resistance to therapeutics remains a critical priority.
We have three research themes in the lab:
- We study the signal transduction pathways altered in melanoma cells compared to normal cells, how to target these pathways and the mechanism by which melanoma cells adapt to therapeutic targeting and acquire resistance. To facilitate these efforts, we have developed in vivo tumor reporter models. These studies are being translated into new clinical trials targeting ErbB3 adaptive responses in order to optimize existing FDA-approved targeted therapies such as MEK inhibitor and to test next-generation BRAF inhibitors in mutant BRAF solid malignancies.
- Besides targeted therapies, immunotherapies have developed as promising treatments for melanoma patients. We are studying ways to induce inflammatory forms of cell death in order to create a more inflamed tumor microenvironment in melanoma. By understanding mechanisms leading to the release of inflammatory factors, we aim to turn 'cold' tumors into 'hot' tumors that are more responsive to immune checkpoint inhibitors.
- Another form of melanoma that is relatively rare but highly deadly is uveal melanoma, cancer of melanocytes in the uvea of the eye. We have active collaborations to study epigenetics, metabolism and tumor dormancy in ocular/uveal melanoma. These efforts are linked to clinical strengths at Jefferson and the Wills Eye Institute and are translating into new clinical trials.
The Aplin laboratory collaborates closely with melanoma clinicians at Jefferson and with national and international melanoma researchers. The laboratory is funded through multiple NIH/NCI, Department of Defense and Foundation grants. Dr. Aplin is a Project Leader on a funded NCI P01 that links the group to the Sidney Kimmel Cancer Center at the Johns Hopkins University, the University of Pennsylvania and The Wistar Institute. Through our research, we aim to promote the bi-directional flow of new discoveries between the laboratory and bedside. Dr. Aplin is also a co-Principal Investigator on a NIH T32 training program in Cancer Biology and has mentored trainees through NIH K99 and F99 awards.
- Mechanisms of response and determinant of resistance to targeted therapies
- Effect of targeted inhibitors on the tumor immune
- Biology of uveal melanoma