Ruth Halaban, PhD

The main areas of research interest are mutations and genomic aberrations associated with malignant transformation and pigmentation and malignant transformation, targeted therapy, and immunobiology of melanoma. Dr. Halaban and her colleagues characterized the mutational landscape of over 400 melanomas. They showed that NF1, a negative regulator of RAS, is the 3rd most frequently mutated gene in melanoma, after BRAF and NRAS. They identified a recurrent UV- signature, activating P29S mutation in RAC1 in 5% of sun-exposed melanomas. Furthermore, in acral melanomas, they revealed late-arising focal amplifications in chr22q11.21, which that include LZTR1 and CRKL, associated with poor outcomes and regional metastases. Most recently, they identified the immunological features associated with immune checkpoint inhibitors (ICI)-induced toxicity. They found that two pretreatment factors in circulation—activated CD4 memory T cell abundance and TCR diversity—are associated with severe irAE development regardless of organ system involvement.

Dr. Halaban group discovered the growth factors requirements for normal human melanocytes and the role of bFGF in transformation to melanomas. They cloned the melanocytes specific genes tyrosinase (TYR) and PMEL (also known as SILV) and showed that mutations in TYR are the cause of albinism.

As the past Director of the Yale SPORE in Skin Cancer and current Co-Director of the Biospecimen Resource Core, Dr. Halaban established operating procedures for the collection of tumors, tissues, blood, normal skin, nevi, and clinical information, and routinely performs protein analyses, whole exome, and RNA sequencing of fresh tumors and matching PBLs. The samples and data are shared with investigators at Yale, nationally and around the worldworldwide.