Department of Internal Medicine,
Divisions of Endocrinology, Diabetes and Metabolism and Oncology
445D McCampbell Hall
1581 Dodd Drive
Columbus, OH 43210
Phone: (614) 292-4356
Fax: (614) 292-1550
Dr. Ringel’s research is aimed at understanding the molecular mechanisms involved in thyroid cancer invasion and metastasis. He also has an active interest in new drug testing for thyroid cancer therapy. The focus of his group has been on clarifying the role of the PI3 kinase/Akt pathway in cancer invasion and metastasis, and on identification of novel endogenous metastasis inhibitor pathways in thyroid cancer. These research interests mesh with his clinical interests in thyroid cancer and allow for translational research opportunities. His work is expanding into other cancers that utilize similar pathways for invasion and metastasis. In addition to his laboratory program, he is involved in a number of clinical research projects including clinical trials and molecular diagnostics evaluations. Several specific laboratory projects that are ongoing include:
Akt in Thyroid Cancer Invasion: Dr. Ringel’s group has been the first to demonstrate a unique subcellular localization of activated Akt in the invasive fronts of thyroid cancers. This process is linked not only to invasion, but also to expression of specific oncogenes. In vitro invasion assays have confirmed these observations and work is ongoing clarifying the role of nuclear Akt in cell migration and in determining regulatory mechanisms for subcellular migration of Akt.
Metastasis Suppressor Pathways: Metastasis suppressors are defined as proteins that inhibit cancer cell metastasis but do not alter tumorigenesis. Dr. Ringel’s group has been focusing on the KiSS-1 metastasis suppressor gene, and its protein product, metastin as a paradigm for this process. Metastin was defined as the endogenous ligand for GPCR54 in 2001. Dr. Ringel’s group demonstrated that expression of this receptor is lost in thyroid cancers with the greatest tendency to metastasize, and that this receptor functions as a metastasis suppressor in thyroid cancer cells. His group is now identifying novel metastasis inhibitory pathways induced by metastin receptor activation in thyroid cancer cells.
Pathway Inhibitors: By defining critical pathways involved in aggressive thyroid cancer behavior, Dr. Ringel’s group is now working in collaboration with other investigators to test a variety of targeted blocking agents for thyroid cancer therapy in vitro and in vivo focusing on cell death and inhibition of metastasis.
The University of Virginia, Charlottesville, VA BA 1987: Chemistry with Biological Chemistry Subspecialization
Pennsylvania State University, Hershey, PA MD 1991
Georgetown University, Washington, DC 1991-1994: Internship and Residency in Internal Medicine
Johns Hopkins University, Baltimore, MD 1994-1997: Clinical and Research Fellowship in Endocrinology and Metabolism
Molecular Biology and Cancer Genetics
Ringel MD, Ladenson, PW, Levine, MA. Molecular Diagnosis of Residual or Recurrent
Thyroid Cancer by Amplification of Thyroglobulin mRNA in Peripheral Blood Cells. J. Clin.
Endocrinol. Metab. 1998;12: 4435-4442.
Ringel MD, Balducci-Silano PL, Anderson JS, Spencer CA, Silverman J, Sparling YH,
Francis GL, Burman, KD, Wartofsky L, Ladenson PW, Levine MA, Tuttle RM. Quantitative reverse transcriptase polymerase chain amplification of circulating thyroglobulin messenger RNA for monitoring patients with thyroid carcinoma. J Clin Endocrinol Metab.1999 84:4037-4042.
Ringel, MD, Greenberg, M, Chen XW, et al. Cytotoxic activity of 2,2, fluorodeoxycytidine against human thyroid cancer cells. Thyroid 2000; 10:865-869
Ringel MD, Anderson JS, Soiuza SL, Burch HB, Tambascia M, Shriver CD, Tuttle RM. Expression of the sodium iodide symporter gene is reduced in papillary thyroid cancer and benign thyroid nodules. Mod Pathol. 2001; 14: 289-296.
Saito J, Kohn AD, Roth RA, Hirai T, Kohn L, Ringel MD. Regulation of thyroid cell cycle
progression and growth by Insulin/IGF-1 via Phosphotidylinositol 3 (OH)-kinase dependent AKT-mediated signaling. Thyroid 2001;11: 339-351.
Ringel MD, Hayre N, Savier B, Burman KD, Shuppert FS, Burch H, Bernet VA, Singer D, Kohn L, Saji M. Akt isoforms are overexpressed and overactivated in sporadic thyroid carcinoma. Cancer Res. 2001:61: 6105-6111.
Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M. Rapid Communication: Metastin Receptor is Overexpressed in Papillary Thyroid Cancer and Signals through MAP Kinase in Thyroid Cancer Cells. J Clin Endocrinol Metabol. 2002; 87:2399-2402.
Germain-Lee EL, Ding C-L, Deng Z, Crane JL, Saji M, Ringel MD, Levine MA. Paternal
imprinting as the basis for TSH resistance in pseudohypoparathyroidism type 1A. Biochem. Biophys. Res. Commun. 2002;296:67-72.
Bauer AJ, Terrell R, Doniparthi NK, Patel A. Tuttle RM, Saji M, Ringel MD, Francis
GL. Vascular endothelial growth factor monoclonal antibody inhibits growth of
anaplastic thyroid cancer xenografts in nude mice. Thyroid. 12:953-961. 2002
Ramljak D, Coticchia CM, Nishanian TG, Saji M, Ringel MD, Conzen SD, Dickson RB. Epidermal growth factor inhibition of c-Myc-mediated apoptosis through Akt and Erk involves Bcl-xL upregulation. Exp Cell Res. 287:397-410. 2003
Vasko V, Saji M, Hardy E, Kruhlak M, Larin A, Savchenko V, Miyagawa M, Isozaki O,
Murakami H, Tsushima T, Burman KD, De Micco C, Ringel MD. AKT activation and localization correlate with tumor invasion and oncogene expression in thyroid cancer. J Med Genet. 41:161-170. 2004.
Braga-Basaria M, Hardy Allrbitton E, Gottfried R, Burman KD, Saji M, Ringel MD. 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) activity against thyroid cancer cell lines correlates with Hsp 90 levels. J Clin Endocrinol Metab. In Press. 2004
Miyagi E, Braga-Basaria M, Hardy E, Jhiang SM, Vasko V, Saji M, Ringel MD. Chronically Overexpressed Ret/PTC-3 selectively activates Akt and increases IRS-2 protein levels in FRTL-5 thyroid cells. Mol Carcin. In Press 2004.