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Michael J. Spinella, Ph.D.

Contact Information:

Professional Interests:

Identification of mechanistic links between stem cell pluripotency and cancer and identification of downstream genes and pathways signaling induced differentiation of human solid tumor cells, especially in response to retinoids; finding causative genes in those tumors that are cured with differentiation and cytotoxic therapy.

Dr. Spinella obtained is Ph.D. in Biochemistry from the Albany Medical College in 1992. 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 November 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 differentiation of human tumor cells and is focused on the effects of the vitamin A derivatives, the retinoids. Anti-tumor activity of retinoids are due in part to their ability to induce tumors to differentiate to a more mature, end stage state. However, the potential of "maturation-based" therapy has been impeded by the toxicity of high dose retinoid treatment. Tumors also develop resistance to retinoids. Identifying the genes engaged in retinoid-mediated differentiation may identify novel chemotherapeutic and chemopreventive targets.

A model system is stem cell-like human embryonal carcinoma which differentiates along a neuronal pathway associated with growth suppression in response to the retinoid all-trans-retinoic acid (RA). 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. Using both candidate gene and de novo screening approaches like microarray analysis, 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. Dr. Spinella's laboratory has recently identified two potential downstream targets, the tumor suppressor protein p53 and the novel nuclear receptor co-repressor RIP140. Ongoing studies wish to identify the mechanisms by which RA affects the activity and expression of these genes and their importance in mediating the anti-tumor effects of retinoids. Long-term goals are to use this system to identify other, potentially novel, genes responsible for tumorigenesis, differentiation, stemness and pharmacologic resistance.

Courses Taught:

Pharmacology 215; Medical Pharmacology
Pharmacology 126; Cancer Biology
Pharmacology 122; Current Approaches in Experimental Therapeutics (Co-Course Director)

Grant Information:

NIH RO1 CA104312 Retinoid tumor differentiation mechanisms PI: Michael Spniella, 07/04-06/09

Lance Armstrong Foundation, Retinoid repressed gene on chromosome 12p, PI:Michael Spinella 01/05-1/08

NIH R21 CA124817-01 Epigenetic reprogramming of malignant stem cells of the testes. PI:Michael Spinella 07/07-6/09