He received postdoctoral training at the Massey Cancer Center and in the Department of Medicine at the Medical College of Virginia and advanced training in Molecular Oncology as a Research Associate in the Department of Medicine and in the Molecular Pharmacology and Therapeutics Program at the Memorial Sloan Kettering Cancer Center. In 1998, Dr. Spinella joined the faculty at Dartmouth Medical School as Assistant Professor in the Department of Pharmacology and Toxicology. Dr Spinella's research addresses the molecular mechanisms of induced growth suppression and differentiation of human tumor cells and is focused on the effects of the vitamin A derivatives, the retinoids. Retinoids have profound effects on cell growth and maturation and have clinical activity in treatment and prevention of various tumors. Anti-tumor activity of retinoids are due in part to their ability to induce tumors to differentiate to a more mature, end stage state.
Tumors also develop resistance to retinoids.
Identifying the genes engaged in retinoid-mediated differentiation may identify novel chemotherapeutic and chemopreventive targets. RA binds and activates the retinoic acid receptor family of transcription factors and in this way regulates the expression of critical target genes. The identity of these genes and the signaling cascades they initiate are largely unknown. Recently, we have used genetic approaches to establish that one specific retinoic acid receptor, RARgamma, likely triggers the differentiation process in embryonal carcinoma cells. Using both candidate gene and de novo screening approaches, the goal of this research is to identify those target genes which are regulated by RA during tumor cell differentiation and to identify those genes which mediate resistance to RA and DNA damaging agents.