Research in the Alani laboratory focuses on understanding epigenetic mechanisms governing the development of human melanoma and other cancers, their responses to therapeutic interventions and the development of innate/acquired resistance to targeted and immunotherapies as well as epigenetic regulation of wound healing, scar formation, and skin aging with the specific goal of moving these basic findings to translational efforts that will directly impact patient care.  Through use of chemical and genetic approaches targeting epigenetic modifiers in clinically relevant in vitro and in vivo systems, the lab explores epigenetic reprogramming in cancer, associated tumor cell plasticity and tumor progression as well as epigenetic processes involved in primary inflammatory skin diseases, wound healing and skin aging. Recent work in the Alani Lab has focused on epigenetic regulation of neoantigens in tumors and the development of novel epigenetic immunotherapies for cancer.

The lab has a particular interest in the development of small molecule targeted epigenetic therapies and their use to determine the role of epigenetic mechanisms in the development and progression of melanoma and the response to targeted and immunotherapies.  These studies have allowed our research team to identify two specific epigenetic modifying complexes which are of particular importance to melanoma biology; the CoREST repressor complex  and the EP300/CBP lysine acetyltransferase (KAT). Recent studies have allowed for the development of a novel dual histone deacetylase and lysine demethylase inhibitor of the CoREST complex, corin, and its use to determine an important role for the CoREST complex in tumor cell plasticity and therapeutic resistance in melanoma. We have also identified the CoREST complex as a specific therapeutic vulnerability in malignant peripheral nerve sheath tumor (MPNST) and atypical teratoid/rhabdoid tumor (ATRT).  Additional work has identified a role for the MITF transcription factor as a mediator of EP300/CBP-associated tumor growth in melanoma and a role for p300 KAT in the regulation of SOX10 stability.  Dr. Alani is the owner of 16 issued and pending US patents related to melanoma biomarkers, novel epigenetic therapies for cancer and skin diseases, and imaging systems to improve melanoma detection.