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Michael J. Spinella, PHD

Associate Professor of Pharmacology & Toxicology

Pharmacology & Toxicology

Albany Medical College, PHD 1992

Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine


Contact Information:

HB 7650
Dept. of Pharmacology and Toxicology
Geisel School of Medicine
Lebanon NH 03756

Office: Rubin 605
Phone: 603-653-9963
Fax: 603-650-1129
Email: michael.spinella@dartmouth.edu

Professional Interests:

Research Interest: Molecular Targets of Cancer Therapy
Research projects in Dr. Spinella's laboratory are focused on identification of mechanistic links between stem cell pluripotency and cancer and the identification of downstream genes and pathways that are induced during chemotherapy that either kill tumors or in other instances lead to their resistance.

Dr. Spinella's research addresses the interplay between the differentiation status of human tumor cells and chemotherapy response. A model system is pluripotent human embryonal carcinoma which are the stem cells of testicular cancer and differentiate along a neuronal pathway associated with growth suppression in response to 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. Using de novo screening approaches like microarray analysis, we have identified novel RA target genes and are in the process of characterizing these genes for their importance in mediating the therapeutic effects of RA. Further we are testing the hypothesis that several of the genes down-regulated by RA, and required to maintain the pluripotent context of these cells, are also responsible for the high cure rates seen in testicular cancer patients treated with conventional chemotherapy (see below).
A second focus in the laboratory relates to the interesting clinical finding that testicular cancer is one of the few human solid tumor that can be cured with high success (~90%) with conventional chemotherapy even when widely metastatic. We have shown through further microarray studies that the master tumor suppressor and transcription factor, p53 is hyperactivated in testicular cancer cells in response to the chemotherapy agent cisplatin and in the process have identified several novel p53 target genes. We are in the process of validating these p53 targets and assessing their importance in the curative response of testicular cancer to therapy. These studies will also expand the known biologic activities of the p53 gene, which is a critical tumor suppressor of all cancers.
A general theme of the lab is then to assess whether therapeutic targets activated in the testicular cancer context can mediate curative responses when targeted more directly and efficiently in other tumor types that are not currently curable, for example lung and brain cancers.

Rotations and Thesis Projects:

1. Determine the importance of DNMT3B as a therapeutic target in testicular cancer and the mechanism responsible for the hypersensitivity of testicular cancer to demethylation agents.
2. Determine the role and mechanism of action of novel p53 target genes during chemotherapy responses in testicular cancer and other solid tumors.
3. Determine the role of novel RA target genes in the induction of differentiation and growth suppression in human embryonal carcinoma and other tumors.

Grant Information:

A New Cancer Therapeutic Target
Role: PI

Alex’s Lemonade Stand
DNA methylation inhibitor therapy for testicular germ cell tumors.
Role: PI

DoD Investigator-Initiated Research Award
Molecular mechanisms of DNA methylation inhibition therapy for testicular cancer in adolescents
Role: PI

Retinoid tumor differentiation mechanisms
Role: PI

Courses Taught:

Pharmacology 215; Medical Pharmacology
PEMM 126; Cancer Biology
PEMM 133; Pharmacology of Drug Development (Course Director)


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 1998, Dr. Spinella joined the faculty at Dartmouth Medical School as Assistant Professor in the Department of Pharmacology and Toxicology.

Selected Publications:


G0S2 Suppresses Oncogenic Transformation by Repressing a MYC-Regulated Transcriptional Program.
Yim CY, Sekula DJ, Hever-Jardine MP, Liu X, Warzecha JM, Tam J, Freemantle SJ, Dmitrovsky E, Spinella MJ
Cancer Res. 2016 Mar 1;76(5):1204-13. doi: 10.1158/0008-5472.CAN-15-2265. Epub 2016 Feb 2.
PMID: 26837760

Epigenetic Targeting of Platinum Resistant Testicular Cancer.
Sonnenburg D, Spinella MJ, Albany C
Curr Cancer Drug Targets. 2015 Dec 22; Epub 2015 Dec 22.
PMID: 26694252

All-trans-retinoic acid antagonizes the Hedgehog pathway by inducing patched.
Busch AM, Galimberti F, Nehls KE, Roengvoraphoj M, Sekula D, Li B, Guo Y, Direnzo J, Fiering SN, Spinella MJ, Robbins DJ, Memoli VA, Freemantle SJ, Dmitrovsky E
Cancer Biol Ther. 2014 Apr;15(4):463-72. doi: 10.4161/cbt.27821. Epub 2014 Feb 4.
PMID: 24496080

Headway and hurdles in the clinical development of dietary phytochemicals for cancer therapy and prevention: lessons learned from vitamin A derivatives.
Yim CY, Mao P, Spinella MJ
AAPS J. 2014 Mar;16(2):281-8. doi: 10.1208/s12248-014-9562-2. Epub 2014 Jan 16.
PMID: 24431081

Serine/threonine kinase 17A is a novel candidate for therapeutic targeting in glioblastoma.
Mao P, Hever-Jardine MP, Rahme GJ, Yang E, Tam J, Kodali A, Biswal B, Fadul CE, Gaur A, Israel MA, Spinella MJ
PLoS One. 2013;8(11):e81803. doi: 10.1371/journal.pone.0081803. Epub 2013 Nov 28.
PMID: 24312360

Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation.
Biswal BK, Beyrouthy MJ, Hever-Jardine MP, Armstrong D, Tomlinson CR, Christensen BC, Marsit CJ, Spinella MJ
PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
PMID: 23300844