Associate Research Professor

582 Biomedical Research Tower
460 W. 12th Ave.
Columbus, OH 43210

614-685-9149
Motoyasu.Saji@osumc.edu

Research interest:
Thyroid cancer

My personal goals in medical science are to identify the mechanisms of tumorigenesis and tumor progression, including dedifferentiation and metastasis, in thyroid cancer, and to apply these results to clinical diagnosis and treatment.  Dr. RIngel and focused on defining the roles of key signaling pathways in thyroid cancer progression, including Akt, Pak and Erk. Using human tumors, in vitro systems and mouse models, we have defined the roles of these and other signaling cascades in thyroid cancer development and progression.

Original Articles

Yu W, Ni Y, Saji M, Ringel MD, Jaini R, Eng C.  Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells.  Hum Mol Genet. 2017 Apr 1;26(7):1365-1375. doi: 10.1093/hmg/ddx037.  PMID: 28164237

Rossfeld KK, Justiniano SE, Ding H, Gong L, Kothandaraman S, Sawant D, Saji M, Wright CL, Kirschner LS, Ringel MD, Tweedle MF, Phay JE.  Biological evaluation of a novel fluorescent-imaging agent for medullary thyroid cancer in an orthotopic model.  J Clin Endocrinol Metab. 2017 Jun 7. doi: 10.1210/jc.2017-00573. [Epub ahead of print]  PMID: 28591772

Wang C, Saji M, Justiniano SE, Yusof AM, Zhang X, Yu L, Fernández S, Wakely P Jr, La Perle K, Nakanishi H, Pohlman N, Ringel MD.   RCAN1-4 is a thyroid cancer growth and metastasis suppressor.  JCI Insight. 2017 Mar 9;2(5):e90651. doi: 10.1172/jci.insight.90651.  PMID: 28289712

Ni Y, Seballos S, Fletcher B, Romigh T, Yehia L, Mester J, Senter L, Niazi F, Saji M, Ringel MD, LaFramboise T, Eng C.  Germline compound heterozygous poly-glutamine deletion in USF3 may be involved in predisposition to heritable and sporadic epithelial thyroid carcinoma. Hum Mol Genet. 2017 Jan 15;26(2):243-257. doi: 10.1093/hmg/ddw382. PMID: 28011713

Justiniano SE, McElroy JP, Yu L, Yilmaz AS, Coombes KR, Senter L, Nagy R, Wakely P Jr, Volinia S, Vinco M, Giordano TJ, Croce CM, Saji M, Ringel MD. Genetic variants in thyroid cancer distant metastases.  Endocr Relat Cancer. 2016 Oct;23(10):L33-6. doi: 10.1530/ERC-16-0351. Epub 2016 Aug 19. PMID: 27542854

Wang Y, Li W, Phay JE, Chen R, Pellegata N, Saji M, Ringel MD, de la Chapelle A, He H.  Primary cell culture systems for human thyroid studies.  Thyroid 2016 June 13. [Epub ahead of print], PMID 27296473

Shirley LA, McCarty S, Yang MC, Saji M, Zhang X, Phay J, Ringel MD, Chen CS.  Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target.  Surgery. 2016 Jan;159 (1):163-70.  Doi: 10.1016/surg.2015.10.016. PMID: 26549818 (Impact Factor, 3.309)

Plews RL, Mohd Yusof A, Wang C, Saji M, Zhang X, Chen CS, Ringel MD, Phay JE. A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth. J Clin Endocrinol Metab. 2015 May;100(5):E748-56. doi: 10.1210/jc.2014-1777. Epub 2015 Feb 24. PubMed PMID: 25710562; PubMed Central PMCID: PMC4422890. (Impact Factor, 6.31)

Guzman N, Agarwal K, Asthagiri D, Yu L, Saji M, Ringel MD, Paulaitis ME. Breast Cancer-Specific miR Signature Unique to Extracellular Vesicles Includes "microRNA-like" tRNA Fragments. Mol Cancer Res. 2015 May;13(5):891-901. doi: 10.1158/1541-7786.MCR-14-0533. Epub 2015 Feb 26. PubMed PMID: 25722304; PubMed Central PMCID: PMC4503213. (Impact Factor, 4.380)

Agarwal K, Saji M, Lazaroff SM, Palmer AF, Ringel MD, Paulaitis ME. Analysis of exosome release as a cellular response to MAPK pathway inhibition. Langmuir. 2015 May 19;31(19):5440-8. doi: 10.1021/acs.langmuir.5b00095. Epub 2015 May 5. PubMed PMID: 25915504. (Impact Factor, 4.457)

Lakshmanan A, Doseff AI, Ringel MD, Saji M, Rousset B, Zhang X, Jhiang SM. Apigenin in combination with Akt inhibition significantly enhances thyrotropin-stimulated radioiodide accumulation in thyroid cells.  Thyroid. 2014 May;24(5):878-87. doi: 10.1089/thy.2013.0614. Epub 2014 Mar 6.  PMID: 24400871 (Impact Factor, 3.843)

Pringle DR, Vasko VV, Yu L, Manchanda PK, Lee AA, Zhang X, Kirschner JM, Parlow AF, Saji M, Jarjoura D, Ringel MD, La Perle KM, Kirschner LS.  Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-specific deletion of Prkar1a and Pten in mice.  J Clin Endocrinol Metab. 2014 May;99(5):E804-12. doi:  10.1210/jc.2013-3101.  PMID: 24512487 (Impact Factor, 6.430)

He H, Bronisz A, Liyanarachchi S, Nagy R, Li W, Huang Y, Akagi K, Saji M, Kula D, Wojcicka A, Sebastian N, Wen B, Puch Z, Kalemba M, Stachlewska E, Czetwertynska M, Dlugosinska J, Dymecka K, Ploski R, Krawczyk M, Morrison PJ, Ringel MD, Kloos RT, Jazdzewski K, Symer DE, Vieland VJ, Ostrowski M, Jarząb B, de la Chapelle A.  SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.  J Clin Endocrinol Metab. 2013 May;98(5):E973-80. doi: 10.1210/jc.2012-3823.  PMID: 23539728 (Impact Factor, 6.430)

Ma Y, McCarty SK, Kapuriya NP, Brendel VJ, Wang C, Zhang X, Jarjoura D, Saji M, Chen CS, Ringel MD.  Development of p21 activated kinase-targeted multikinase inhibitors that inhibit thyroid cancer cell migration.  J Clin Endocrinol Metab. 2013 Aug;98(8):E1314-22. doi: 10.1210/jc.2012-3937.   PMID: 23709653 (Impact Factor, 6.430)

Ding H, Yusof AM, Kothandaraman S, Saji M, Wang C, Kumar K, Milum K, Carleton M, Pan X, Ringel MD, Tweedle MF, Phay JE.  Localization of CaSR antagonists in CaSR-expressing medullary thyroid cancer.  J Clin Endocrinol Metab. 2013 Nov;98(11):E1722-9. doi: 10.1210/jc.2013-1756. Epub 2013 Sep 12.  PMID:24030941 (Impact Factor, 6.430)

Yusof AM, Kothandaraman S, Zhang X, Saji M, Ringel MD, Tweedle MF, Phay JE.  Development of a calcium-sensing receptor molecular imaging agent.  Surgery. 2013 Dec;154(6):1378-84; discussion 1384. doi: 10.1016/j.surg.2013.06.044.  PMID: 24238055 (Impact Factor, 3.373)

He X, Saji M, Radhakrishnan D, Romigh T, Ngeow J, Yu Q, Wang Y, Ringel MD, Eng C.  PTEN lipid phosphatase activity and proper subcellular localization are necessary and sufficient for down-regulating AKT phosphorylation in the nucleus in Cowden syndrome.  J Clin Endocrinol Metab. 2012 Nov;97(11):E2179-87. doi: 10.1210/jc.2012-1991. Epub 2012 Sep 7.  PMID: 22962422

Shen R, Liyanarachchi S, Li W, Wakely PE Jr, Saji M, Huang J, Nagy R, Farrell T, Ringel MD, de la Chapelle A, Kloos RT, He H.  MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases. Thyroid. 2012 Jan;22(1):9-16. PMID 22136206

Koh YW, Shah MH, Agarwal K, McCarty SK, Koo BS, Brendel VJ, Wang C, Porter K, Jarjoura D, Saji M, Ringel MD.  Sorafenib and Mek inhibition is synergistic in medullary thyroid carcinoma in vitro.  Endocr Relat Cancer. 2012 Jan 9;19(1):29-38.  PMID: 22109971

Saji M, Narahara K, McCarty SK, Vasko VV, La Perle KM, Porter K, Jarjoura D, Lu C, Cheng SY, Ringel MD. Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer.  Oncogene, 2011, 30:4307-4315, PMID 21532619

McCarty SK, Saji M, Zhang X, Jarjoura D, Fusco A, Vasko VV, Ringel MD. Group I p21-activated kinases regulate thyroid cancer cell migration and are overexpressed and activated in thyroid cancer invasion.   Endocr Relat Cancer, 2010, 17: 989-999   PMID 20817787

Jensen K, Patel A, Larin A, Hoperia V, Saji M, Bauer A, Yim K, Hemming V, Vasko V.  Human herpes simplex viruses in benign and malignant thyroid tumours. J Pathol 2010 221:193-200

Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J, Sammet S, Hall NC, Wakely PE Jr., Vasko VV, Saji M, Snyder PJ, Wei L, Arbogast D, Collamore M, Wright JJ, Moley JF, Villalona-Calero MA, Shah MH.  Phase II Clinical trial of Sorafenib in metastatic medullary thyroid Cancer,  J. Clin Oncol.  2010 28:2323-2330

Nadella KS, Saji M, Jacob NK, Pavel E, Ringel MD, Kirschner LS, Regulator of actin function by protein kinase A-mediated phosphorylation of Limk1.  EMBO Rep 2009 10: 599-605

Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE Jr, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH. Phase II Trial of Sorafenib in Metastatic Thyroid Cancer. J Clin Oncol. 2009 27:1675-84

Espinosa AV, Shinohara M, Porchia LM, Chung Yj, McCarty SK, Saji M, Ringel MD.  Regulator of calcineurin 1 modulates cancer cell migration in vitro.  Clin Exp Metastasis, 2009, 26: 517-26

Wang PS, Chou FS, Bloomston M, Vonau MS, Saji M, Espinosa A, Pinzone JJ.  Thiazolidinediones Downregulate Wnt/beta-Catenin Signaling Via Multiple Mechanisms in Breast Cancer Cells.  J Surg Res. 2009 153: 127-35

Wang PS, Chou FS, Porchia L, Saji M, Pinzone JJ.  Troglitazone inhibits cell migration, adhesion, and spreading by modulating cytoskeletal rearrangement in human breast cancer cells.  Mol Carcinog. 2008 47: 905-15

Porchia LM, Guerra M, Wang YC, Zhang Y, Espinosa AV, Shinohara M, Kulp SK, Kirshner LS, Saji M, Chen CS, Ringel MD.  OSU03012, a celecoxib derivative, directly targets p21 activated kinase. Mol Pharmacol 72:1124-31, 2007

McCall KD, Harii N, Lewis CJ, Malgor R, Bae Kim W, Saji M, Kohn AD, Moon RT, Kohn LD, High basal levels of functional toll-like receptor 3 (TLR-3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazol together with cell proliferation and migration. Endocrinology 148: 4226-37, 2007

Vasko V, Espinosa AV, Scouten W, He H, Auer H, Liyanarachchi S, Larin A, Savchenko V, Francis GL, dela Chapelle A, Saji M, Ringel MD.  Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.  Proc Natl Acad Sci USA 104: 2803-8, 2007

Giuliani C. Saji M, Bucci I, Fiore G, Liberatore M, Singer DS, Monaco F, Kohn LD, Napolitano G.  Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-1 in FRTL-5 thyroid cells.  J Endocrinol 189: 605-15, 2006

Germain-Lee EL, Schwindinger W, Crane JL, Zewdu R, Zweifel LS, Wand G, Uso DL, Saji M, Ringel MD, Levine MA.  A mouse model of Albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene.  Endocrinology 146:4697-709

Acharyya S, Butchback M, Sahnek Z, Wang H, Saji M, Carathers M, Ringel, MD, Burghes AH, Rafael-Fortney JA, Guttridge DC.  Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell.  8:421-32, 2005

Kim CS, Vasko VV, Kato Y, Kruhlak M, Saji M, Cheng S-Y, Ringel MD  AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma.  Endocrinology 146: 4456-63, 2005

Stathatos N, Bourdeau I, Espinosa AV, Saji M, Vasko VV, Burman KD, Stratakis CA, Ringel MD.  KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity.  J Clin Endocrinol Metab 90: 5432-5440, 2005

Saji M, Vasko V, Kada F, Allbritton EH, Burman KD, Ringel MD.  Akt1 contains a functional leucin-rich nuclear export sequence.  Biochem Biol Res Commun 332: 167-173. 2005

Harii N, Lewis CJ, Vasko V, McCall K, Benavides-Peralta U, Sun X, Ringel MD, Saji M, Giuliani C, Napolitano G, Goetz DJ, Kohn LD.  Thyrocytes Express a Functional Toll-Like Receptor 3: Overexpression Can Be Induced by Viral Infection and Reversed by Phenylmethimazole and Is Associated with Hashimoto's Autoimmune Thyroiditis. Mol Endocrinol. 19:1231-50. 2005

Weber F, Chen L, Aldred MA, Morrison CD, Frilling A, Saji M, Schuppert F, Broelsch CE, Ringel MD, Eng C  Genetic clssification of benign and malignant thyroid follicular neoplasia based on a here-gene combination.  J Clin Endocrinol Metab 90: 2512-2521. 2005

Cristofaro JD, Vasko V, Savchenko V, Cherenko S, Larin A, Ringel MD, Saji M, Marcy M, Henry JF, Carayon P, De Micco C.  ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients.  Endocr Relat Cancer 12: 173-183. 2005

Vasko VV, Gaudart J, Allasia C, Savchenko V, Di Cristofaro J, Saji M, Ringel MD, De Micco C.  Thyroid follicular adenomas may display features of follicular carcinoma and follicular variant of papillary carcinoma. Eur J Endocrinol 151: 779-86. 2004

Perlman A, Kolachana P, Lawsin L, Saji M, Moore J, Ringel, MD. Angiontensin II transactivates the EGF receptor and both PI3 Kinase and MAP Kinase in Murine Mesangial Cells.  Ann Clin Lab Sci, 34:277-286, 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 Carcinog. 41:98-107. 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. 84:2982-2988. 2004.

Umbricht, CB, Conrad GT, Clark DP, Westra WH, Smith DC, Zahurak M, Saji M, Smallridge RC, Goodman S, Zeiger MA  Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors.  Clin Can Res 10: 5762-68, 2004

Vasko V, Saji M, Hardy E, Kruhlak M, Larin A, Savchenko V, Miyakawa 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

Umbricht, CB, Conrad GT, Clark DP, Westra WH, Smith DC, Zahurak M, Saji M, Smallridge RC, Goodman S, Zeiger MA  Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors.  Clin Can Res 10: 5762-68, 2004

Vasko V, Saji M, Hardy E, Kruhlak M, Larin A, Savchenko V, Miyakawa 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

Burnett MS, Durrani S, Stabile E, Saji M, Lee CW, Kinnaird TD, Hoffman EP,  Epstein SE.  Murine cytomegalovirus infection increases aortic expression of proatherosclerotic genes.  Circulation 10: 893-897, 2004

Stabile E, Zhou YF, Saji M, Castagna M, Shou M, Dinnarid TD, Baffour R, Ringel MD, Epstein SE, Fuchs S.  Akt controls Vascular Smooth Muscle cell proliferation In Vitro and In Vivo by delaying G1/S exit.  Cir Res 93: 1059-1065, 2003

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 in mammary epithelial cells.  Exp Cell Res 287: 397-410, 2003

Bauer AJ, Patel A, Terrell R, Doniparthi K, Saji M, Ringel D, Tuttle MR, Francis GL. Systemic administration of vascular endothelial growth factor monoclonal antibody reduces the growth of papillary thyroid carcinoma in a nude mouse model.  Ann Clin Lab Sci 33: 192-199, 2003

Bauer AJ, Terrell R, Doniparthi NK, Patel A, Terrell R, Tuttle M, 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

Bernet VJ, Anderson J, Vaishnav Y, Solomon B, Adair CF, Saji M, Burman KD, Burch HB, Ringel MD.  Determination of galectin-3 messenger ribonucleic acid overexpression in papillary thyroid cancer by quantitative reverse transcription-polymerase chain reaction.  J Clin Endocinol Metab 87: 4792-96, 2002

Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M.  Metastin Receptor is Overexpressed in Papillary Thyroid Cancer and Activates MAP Kinase in Thyroid Cancer Cells  J Clin Endocrinol Metab 87:2399-2402, 2002

Germain-Lee EL, Ding CL, Deng Z, Crane JL, Saji M, Ringel MD, Levine MA., Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a.  Biochem Biophys Res Commun. 296:67-72, 2002

Ringel MD, Hyre N, Saito J, Saunier B, Schuppert F, Burch H, Bernet V, Burman KD, Kohn LD, Saji M.  Overexpression and overactivation of Akt in thyroid carcinoma.  Cancer Research 61: 6105-11, 2001

Saito J, Kohn AD, Roth RA, Noguchi Y, Tatsumo I, Hirai A, Suzuki K, Kohn LD, Saji M, Ringel MD.  Regulation of FRTL-5 thyroid cell growth by phosphatidylinositol (OH) 3 kinase-dependent Akt-mediated signaling.  Thyroid 11: 339-351, 2001

Siddiqui MT, Green KL, Clark DP, Xydas S, Udelsman R, Smallridge RC, Zeiger MA, Saji M.  Humnan telomerase reverse transcriptase (hTERT) gene expression in Diff-Quik stained FNA samples from thyroid nodules.  Diag Mol Pathol 10: 123-129, 2001

Ringel MD, Greenberg M, Chen, XW, Hayre N, Suzuki K, Priebat D, Saji M, Burman KD.  Cytotoxic activity of 2’,2’-difluorodeoxycytidine (Gemcitabine) in poorly differentiated thyroid carcinoma cells. Thyroid 10: 865-869, 2000

Kirshner S, Palmer, L, Boor, J, Saji M, Kohn LD, Singer DS.  Major histocompatibility class I gene transcription in thyrocytes:  A series of interacting regulatory DNA sequence elements mediate throtropin/cyclic adenosine 3’,5’-monophosphate repression. Mol Endocrinol 14: 82-98, 2000

Zeiger MA, Smallridge RC, Clark DP, Lang, C-K, carty SE, Watson CG, Udelsman R, Saji M  Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms. Surgery 126:1195-1199, 1999

Saji M, Xydas S, Westra WH, Liang C-K, Clark DP, Udelsman R, Umbricht CB, Sukumar S, Zeiger MA. Human telomerase reverse transcriptase (hTERT) gene  expression in thyroid neoplasms. Clin Cancer Res 5:1483-1489, 1999

Dome JS, Chung S, Bergemann T, Umbricht CB, Saji M, Carey LA, Grundy PE, Perlman EJ, Breslow NE, Sukumar S, the national Wilms Tumor Study Group.  Telomerase reverse transcriptase (hTERT) mRNA level correlates with outcome in patients with Wilms tumor. Cancer Res 59: 4301-4307, 1999

Chun YS, Saji M, Zeiger MA.  Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. Surgery 124:1100-1105, 1998

Taniguchi SI, Shong M, Giuliani C, Napolitano G, Saji M, Montani V, Suzuki K, Singer DS, Kohn LD.  Iodide suppression of major histocompatibility class I gene expression in thyroid cells involves enhancer A and the transcription factor NF-kappa B. Mol Endocrinol 12:19-33, 1998

Ringel MD, Saji M, Schwindinger WF, Segev D, Zeiger MA, Levine MA.  Absence of activating mutations of the genes encoding the alpha-subunits of G11 and Gq in thyroid neoplasia. J Clin Endocrinol Metab 83:554-559, 1998

Segev DL, Saji M, Phillips GS, Westra WH, Takiyama Y, Piantadosi S, Smallridge RC, Nishiyama RH, Udelsman R, Zeiger MA.  Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid. J Clin Endocrinol Metab 83:2036-2042, 1998

Halachmi N, Halachmi S, Evron E, Cairns P, Okami K, Saji M, Westra WH, Zeiger MA, Jen J, Sidransky D.  Somatic mutations of the PTEN tumor suppressor gene in sporadic follicular thyroid tumors. Gene Chromosome Cancer 23:239-243, 1998

Montani V, Shong M, Taniguchi SI, Suzuki K, Giuliani C, Napolitano G, Saito J, Saji M, Fiorentino B, Reimold AM, Singer DS, Kohn LD.  Regulation of major histocompatibility class II gene expression in FRTL-5 thyrocytes: opposite effects of interferon and methimazole. Endocrinology 139:290-302, 1998

Montani V, Taniguchi SI, Shong M, Suzuki K, Ohmori M, Giuliani C, Napolitano G, Saji M, Fiorentino B, Reimold AM, Ting JP, Kohn LD, Singer DS.  Major histocompatibility class II HLA-DR alpha gene expression in thyrocytes: counter regulation by the class II transactivator and the thyroid Y box protein. Endocrinology 139:280-289, 1998

Graff JR, Greenberg VE, Herman JG, Westra WH, Boghaert ER, Ain KB, Saji M, Zeiger MA, Zimmer SG, Baylin SB.  Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle's cell, and poorly differentiated human thyroid carcinoma. Cancer Res 58:2063-2066, 1998

Ringel MD, Schwindinger WF, Saji M, Zeiger MA, Levine MA.  Determination of transgene copy number and expression level using denaturing gradient gel electrophoresis. Biotechniques 24:126, 128-131, 1998

Takiyama Y, Saji M, Clark DP, Phillips GS, Segev DL, Smallridge RC, Westra WH, Udelsman R, Zeiger MA.  Polymerase chain reaction-based microsatellite analysis of fine-needle aspirations from Hurthle cell neoplasms. Thyroid 7:853-7, 1997

Saji M, Westra WH, Chen H, Umbricht CB, Tuttle RM, Box MF, Udelsman R, Sukumar S, Zeiger MA.  Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid. Surgery 122:1137-1140, 1997

Schaaf L, Leiprecht A, Saji M, Hubner U, Usadel KH, Kohn LD.  Glycosylation variants of human TSH selectively activate signal transduction pathways. Mol Cell Endocrinol 132:185-94, 1997

Yano K, Kohn LD, Saji M, Okuno A, Cutler GB, Jr.  Phe576 plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone/chorionic gonadotropin receptor. J Clin Endocrinol Metab 82:2586-2591, 1997

Saji M, Shong M, Napolitano G, Palmer LA, Taniguchi SI, Ohmori M, Ohta M, Suzuki K, Kirshner SL, Giuliani C, Singer DS, Kohn LD.  Regulation of major histocompatibility complex class I gene expression in thyroid cells. Role of the cAMP response element-like sequence. J Biol Chem 272:20096-20107, 1997

Zeiger MA, Saji M, Gusev Y, Westra WH, Takiyama Y, Dooley WC, Kohn LD, Levine MA.  Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice. Endocrinology 138:3133-3140, 1997

Umbricht CB, Saji M, Westra WH, Udelsman R, Zeiger MA, Sukumar S.  Telomerase activity: a marker to distinguish follicular thyroid adenoma from carcinoma. Cancer Res 57:2144-2147, 1997

Zeiger MA, Takiyama Y, Bishop JO, Ellison AR, Saji M, Levine MA.  Adenoviral infection of thyroid cells: a rationale for gene therapy for metastatic thyroid carcinoma. Surgery 120:921-925, 1996

Califano JA, Johns MMr, Westra WH, Lango MN, Eisele D, Saji M, Zeiger MA, Udelsman R, Koch WM, Sidransky D.  An allelotype of papillary thyroid cancer. Int J Cancer 69:442-444, 1996

Zeiger MA, Saji M, Caturegli P, Westra WH, Kohn LD, Levine MA.  Transformation of rat thyroid follicular cells stably transfected with cholera toxin A1 fragment. Endocrinology 137:5392-5399, 1996

Laglia G, Zeiger MA, Leipricht A, Caturegli P, Levine MA, Kohn LD, Saji M.  Increased cyclic adenosine 3',5'-monophosphate inhibits G protein-coupled activation of phospholipase C in rat FRTL-5 thyroid cells. Endocrinology 137:3170-3176, 1996

Yano K, Kohn LD, Saji M, Kataoka N, Okuno A, Cutler GB, Jr.  A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene. Biochem Biophys Res Commun 220:1036-1042, 1996

Yano K, Saji M, Hidaka A, Moriya N, Okuno A, Kohn LD, Cutler GB, Jr.  A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty. J Clin Endocrinol Metab 80:1162-1168, 1995

Giuliani C, Saji M, Napolitano G, Palmer LA, Taniguchi SI, Shong M, Singer DS, Kohn LD.  Hormonal modulation of major histocompatibility complex class I gene expression involves an enhancer A-binding complex consisting of Fra-2 and the p50 subunit of NF-kappa B. J Biol Chem 270:11453-11462, 1995

Bifulco M, Perillo B, Saji M, Laezza C, Tedesco I, Kohn LD, Aloj SM.  Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in FRTL-5 cells. I. Identification and characterization of a cyclic AMP-responsive element in the rat reductase promoter. J Biol Chem 270:15231-15236, 1995

Saji M, Levine MA, Zeiger MA.  An in vitro model of thyroid neoplasia: permanently transfected FRTL-5 cells with thyroglobulin promoter-cholera toxin A1 subunit minigene. Surgery 116:1048-52; discussion 1052-1053, 1994

Shimura H, Okajima F, Ikuyama S, Shimura Y, Kimura S, Saji M, Kohn LD.  Thyroid-specific expression and cyclic adenosine 3',5'-monophosphate autoregulation of the thyrotropin receptor gene involves thyroid transcription factor-1. Mol Endocrinol 8:1049-1069, 1994

Yano K, Hidaka A, Saji M, Polymeropoulos MH, Okuno A, Kohn LD, Cutler GB, Jr.  A sporadic case of male-limited precocious puberty has the same constitutively activating point mutation in luteinizing hormone/choriogonadotropin receptor gene as familial cases. J Clin Endocrinol Metab 79:1818-1823, 1994

Grollman EF, Saji M, Shimura Y, Lau JT, Ashwell G.  Thyrotropin regulation of sialic acid expression in rat thyroid cells. J Biol Chem 268:3604-3609, 1993

Saji M, Moriarty J, Ban T, Kohn LD, Singer DS.  Hormonal regulation of major histocompatibility complex class I genes in rat thyroid FRTL-5 cells: thyroid-stimulating hormone induces a cAMP-mediated decrease in class I expression. Proc Natl Acad Sci USA 89:1944-1948, 1992

Saji M, Moriarty J, Ban T, Singer DS, Kohn LD.  Major histocompatibility complex class I gene expression in rat thyroid cells is regulated by hormones, methimazole, and iodide as well as interferon. J Clin Endocrinol Metab 75:871-878, 1992

Saji M, Akamizu T, Sanchez M, Obici S, Avvedimento E, Gottesman ME, Kohn LD.  Regulation of thyrotropin receptor gene expression in rat FRTL-5 thyroid cells. Endocrinology 130:520-533, 1992

Tahara K, Grollman EF, Saji M, Kohn LD.  Regulation of prostaglandin synthesis by thyrotropin, insulin or insulin-like growth factor-I, and serum in FRTL-5 rat thyroid cells. J Biol Chem 266:440-448, 1991

Isozaki O, Tsushima T, Emoto N, Saji M, Tsuchiya Y, Demura H, Sato Y, Shizume K, Kimura S, Kohn LD.  Methimazole regulation of thyroglobulin biosynthesis and gene transcription in rat FRTL-5 thyroid cells. Endocrinology 128:3113-3121, 1991

Saji M, Kohn LD.  Insulin and insulin-like growth factor-I inhibit thyrotropin-increased iodide transport in serum-depleted FRTL-5 rat thyroid cells: modulation of adenosine 3',5'-monophosphate signal action. Endocrinology 128:1136-1143, 1991

Saji M, Ikuyama S, Akamizu T, Kohn LD.  Increases in cytosolic Ca++ down regulate thyrotropin receptor gene expression by a mechanism different from the cAMP signal. Biochem Biophys Res Commun 176:94-101, 1991

Akamizu T, Ikuyama S, Saji M, Kosugi S, Kozak C, McBride OW, Kohn LD.  Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies. Proc Natl Acad Sci USA 87:5677-5681, 1990

Tsuchiya Y, Saji M, Isozaki O, Arai M, Tsushima T, Shizume K.  Effect of lithium on deoxyribonucleic acid synthesis and iodide uptake in porcine thyroid cells in culture. Endocrinology 126:460-465, 1990

Saji M, Kohn LD.  Effect of hydrocortisone on the ability of thyrotropin to increase deoxyribonucleic acid synthesis and iodide uptake in FRTL-5 rat thyroid cells: opposite regulation of adenosine 3',5'-monophosphate signal action. Endocrinology 127:1867-1876, 1990

Bellur S, Tahara K, Saji M, Grollman EF, Kohn LD.  Repeatedly passed FRTL-5 rat thyroid cells can develop insulin and insulin-like growth factor-I-sensitive cyclooxygenase and prostaglandin E2 isomerase-like activities together with altered basal and thyrotropin-responsive thymidine incorporation into DNA. Endocrinology 127:1526-1540, 1990

Akamizu T, Saji M, Kohn LD.  A microsequencing approach to identify proteins which appear to interact with thyrotropin in rat FRTL-5 thyroid cells. Biochem Biophys Res Commun 170:351-358, 1990

Tahara K, Saji M, Aloj SM, Kohn LD.  The arachidonic acid signal system in the thyroid: regulation by thyrotropin and insulin/IGF-I. Adv Exp Med Biol 261:295-326, 1989

Nomura K, Suzuki H, Saji M, Horiba N, Ujihara M, Tsushima T, Demura H, Shizume K.  High serum progesterone in hyperthyroid men with Graves' disease. J Clin Endocrinol Metab 66:230-232, 1988

Miyakawa M, Saji M, Tsushima T, Wakai K, Shizume K.  Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels. J Clin Endocrinol Metab 67:973-978, 1988

Tsushima T, Arai M, Saji M, Ohba Y, Murakami H, Ohmura E, Sato K, Shizume K.  Effects of transforming growth factor-beta on deoxyribonucleic acid synthesis and iodine metabolism in porcine thyroid cells in culture. Endocrinology 123:1187-1194, 1988

Saji M, Isozaki O, Tsushima T, Arai M, Miyakawa M, Ohba Y, Tsuchiya Y, Sano T, Shizume K.  The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells. Acta Endocrinol (Copenh) 119:145-151, 1988

Saji M, Tsushima T, Isozaki O, Murakami H, Ohba Y, Sato K, Arai M, Mariko A, Shizume K.  Interaction of insulin-like growth factor I with porcine thyroid cells cultured in monolayer. Endocrinology 121:749-756, 1987

Emoto N, Tsushima T, Shizume K, Tanaka T, Saji M, Ohba Y, Wakai K, Arai M, Ohmura E.  Biological activities of human growth hormone and its derivatives estimated by measuring DNA synthesis in Nb2 node rat lymphoma cells. Acta Endocrinol (Copenh) 114:283-291, 1987

Sato K, Fujii Y, Kasono K, Saji M, Tsushima T, Shizume K.  Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 a in fetal mouse bones. Biochem Biophys Res Commun 138:618-624, 1986

Isozaki O, Tsushima T, Shizume K, Saji M, Ohba Y, Emoto N, Sato K, Sato Y, Kusakabe K.  Thyroid-stimulating antibody bioassay using porcine thyroid cells cultured in follicles. J Clin Endocrinol Metab 61:1105-1111, 1985

Isozaki O, Tsushima T, Sato K, Saji M, Ohba Y, Emoto N, Sato Y, Shizume K.  Triiodothyronine binding immunoglobulin in a euthyroid man without apparent thyroid disease; its properties and effects on triiodothyronine metabolism. Acta Endocrinol (Copenh) 108:498-503, 195

Review Articles

Giuliani C, Saji M, Bucci I, Napolitano G.  Bioassays for TSH receptor autoantibodies, from FRTL-5 cells to TSH receptor–LH/CG receptor chimeras: the contribution of Leonard D. Kohn  2016 Frontiers in Endocrinology [Epub ahead of publication]  Front Endocrinol (Lausanne). 2016 Jul 25;7:103. doi: 10.3389/fendo.2016.00103. eCollection 2016. Review. PMID: 27504107 

Saji M, Ringel MD. The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. Mol Cell Endocrinol. . [Epub ahead of print] PubMed PMID: 19897009.

Vasko VV, Saji M. Molecular mechanisms involved in differentiated thyroid cancer invasion and metastasis. Curr Opin Oncol. 2007 Jan;19(1):11-7. Review. PubMed PMID: 17133106.

Shinohara M, Chung YJ, Saji M, Ringel MD. AKT in thyroid tumorigenesis and progression. Endocrinology. 2007 Mar;148(3):942-7. Epub 2006 Aug 31. Review. PubMed PMID: 16946008.

Kada F, Saji M, Ringel MD. Akt: a potential target for thyroid cancer therapy. Curr Drug Targets Immune Endocr Metabol Disord. 2004 Sep;4(3):181-5. Review. PubMed PMID: 15379721.

Saji M, Ringel MD, Akt signaling in thyroid neoplasia.  Cur Opin Endocrinol Diabetes, 11:197-204, 2004. Review

Kohn LD, Shimura H, Shimura Y, Hidaka A, Giuliani C, Napolitano G, Ohmori M, Laglia G, Saji M. The thyrotropin receptor. Vitam Horm. 1995;50:287-384. Review. PubMed PMID: 7709602.

Saji M, Ikuyama S, Shimura H, Ban T, Kosugi S, Hidaka A, Okajima F, Shimura Y, Giuliani C, Napolitano G, Tahara K, Akamizu T Kohn LD: Structure and regulated expression of the TSH receptor gene: Differences and similarities to gonadotropin receptors. In Lustbader JW, Puett JD, Ruddon R (eds): Glycoprotein Hormones: Structure, Function, and Clinical Implications. Serona Synposia. Springer Verlag, New York, 1993. Review

Kohn LD, Ban T, Okajima F, Shimura H, Shimura Y, Hidaka A, Giuliane C, Napolitano G, Kosugi S, Ikuyama S, Saji M: Relationship of the structure, function, and regulation of the thyrotropin receptor to its role in thyroid autoimmune disease. In Polli, EE (ed): Molecular Bases of Human Diseases. Excerpta Medica, Elsevier, North Holland, International Congress Seriesk, vol 1029, 141-149, 1993. Review

Kohn LD, Ban T, Okajima F, Shimura H, Shimura Y, Hidaka A, Giuliane C, Napolitano G, Kosugi S, Ikuyama S, Akamizu T, Tahara K, Saji M: Cloning and regulation of glycoprotein hormone receptor genes. In Weintraub B (ed): Molecular Endocrinology: Basic Concepts and Clinical Correlations. Raven Press, New York, 1993. Review

Kohn LD, Kosugi S, Ban T, Saji M, Ikuyama S, Giuliani C, Hidaka A, Shimura H, Akamizu T, Tahara K, et al. Molecular basis for the autoreactivity against thyroid stimulating hormone receptor. Int Rev Immunol. 1992;9(2):135-65. Review. PubMed PMID: 1283175.

Akamizu T, Saji M, Ikuyama S, Kosugi S, Tahara K, Kohn LD. The TSH receptor in autoimmune Basedow's disease. Exp Clin Endocrinol. 1991 May;97(2-3):153-9. Review. PubMed PMID: 1915626.

Kohn LD, Akamizu T, Saji M, Ikuyama S, Bellur S, Tahara K The cloning road to the TSH receptor and autoimmune Graves' disease. In Demaine AG, Banga JP, McGregor AM (eds): The Molecular Biology of Autoimmune Disease. NATO ASI series, vol H38, Springer-Verlag, Berlin, 363-378, 1989

Tahara K, Saji M, Aloj SA, Kohn LD. The arachidonic acid signal system in the thyroid: Regulation by thyrotropin and insulin/IGF-I. In Ekholm R, Kohn LD, Wollman S (eds): Control of the Thyroid Gland: Regulation of its Normal Growth and Function. Advances in Experimenta Medicine and Biology, vol 261. Plenum Publishing Corp., New York, 295-326, 1989, review

Kohn LD, Saji M, Akamizu T, Ikuyama S, Isozaki O, Kohn AD, Santisteban P, Chan, JY, Bellur S, Rotella CM, et al. Receptors of the thyroid: the thyrotropin receptor is only the first violinist of a symphony orchestra. Adv Exp Med Biol. 1989;261:151-209. PubMed PMID: 2561506.