Stephen J. Marx, M.D.


MDB
METABOLIC DISEASES BRANCH
NIDDK, National Institutes of Health
Building 10 , Room 9C103
10 Center Dr.
Bethesda, MD 20814
Tel: 301-496-5051
Fax: 301-496-0200
Email: marxs@mail.nih.gov

Stephen J. Marx, M.D.

Education / Previous Training and Experience:
B.A., Yale, 1964
M.D., Johns Hopkins, 1968


Research Statement:

The Genetics and Endocrinology Section studies the genetic bases of primary hyperparathyroidism and its relations to other neoplastic disorders. We have cloned the gene for multiple endocrine neoplasia type 1 and found that it is implicated in many non-hereditary tumors. This tumor suppressor gene encodes a novel protein, menin. We are studying the actions of menin protein by yeast two-hybrid, micro-array, knockout, and other approaches. We have identified an important interaction of menin with junD, a nuclear transcription factor.



Selected Publications:
Eastell E, Arnold A, Brandi ML, Brown E, D’Amour P, Hanley DA, Rao DS, Rubin M, Goltzman D, Silverberg S, Marx SJ, Peacock M, Moselikde L, Bouillon R, Lewiecki EM. Diagnosis of asymptomatic primary hyperparathyroidism: Proceedings of the third international workshop. J Clin Endocrinol Metab 94: 340-50, 2009.

Bilezekian JP, Khan AA, Potts JT jr on behalf of the Third International Workshop on Management of Asymptomatic Primary Hyperparathyroidism. Guidelines for the management of asymptomatic primary hyperparathyroidism: Summary statement from the Third International Workshop. J Clin Endocrinol Metab 94: 335-39, 2009.

Agarwal SK, Mateo C, Marx SJ. Rare germline mutations in cyclin-dependent kinase inhibitor genes in MEN1 and related states. J Clin Endocrinol Metab Online 1/13/09 as doi:1210/jc.2009-2083359.

Gagel RF and Marx S J. Multiple endocrine neoplasia. In: Williams Textbook of Endocrinology. 11th Edition. Edited by Kronenberg HM et al Saunders, Philadelphia, 2007, pp 1705-46.

Arnold A, Marx SJ. Familial hyperparathyroidism (Including MEN, FHH, and HPT-JT). Primer on the Metabolic Bone Diseases and Mineral Metabolism 7th Edition. Ed Rosen C et al. Am Soc Bone Min Res. Wash DC, 361-7, 2009.

Ozawa A, Agarwal SK, Mateo CM, Burns AL, Rice TS, Kennedy PA, Quigley CM, Simonds WF, Weinstein LS, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ The parathyroid/pituitary variant of MEN1 usually has causes other than p27Kip1 mutations J Clin Endocrinol Metab 92: 1948-51, 2007

Agarwal SK, Impey S, McWeeney S, Scacheri PC, Collins FS, Goodman RH, Spiegel AM, Marx SJ Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation. Neoplasia 9: 101-107, 2007

Agarwal SK, Scacheri PC, Rice TS, Kennedy PA, Ozawa A, Burgess-Hickman A, PopsonSA, Burns AL, Mateo C, Simonds WF, Oliver B, Libutti SK, Novotny EA, Halawi MJ, Ji Y, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ. MEN1 gene: mutation and pathophysiology. Ann d’Endocrinol 67 Suppl 4: 1S12-1S13, 2006.

Marx SJ. Molecular genetics of multiple endocrine neoplasia type 1 and type 2. Nature Reviews Cancer 5: 367-75, 2005. Correction 5:663, 2005.

Marx SJ and Simonds WF Hereditary hormone excess: Genes, molecular pathways, and syndromes. Endocr Rev 26: 615-61, 2005.

Scacheri PC, Crabtree JS, Kennedy AL, Swain GP, Ward JM, Marx SJ, Spiegel AM, Collins FS. Homozygous loss of menin is well tolerated in liver, a tissue not affected in MEN1. Mam Genome 15; 872-77, 2004.

Agarwal SK, Novotny EA, Crabtree JS, Weitzman JB, Yaniv M, Burns AL, Chandrasekharappa SK, Collins FS, Spiegel AM, Marx SJ. Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. Proc Nat Acad Sci USA 100: 10770-5, 2003.

Crabtree JS, Scacheri PC, Ward JM, McNally SR, Swain GP, Montagna C, Hager JH, Hanahan D, Edlund H, Magnuson MA, Garrett-Beal L, Burns AL, Reid T, Chandrasekharappa SC, Marx SJ, Spiegel AM, Collins FS. Of mice and MEN1: Insulinomas in a conditional mouse knockout. Molec Cell Biol 23; 6075-85, 2003.

Sukhodolets KE, Hickman AB, Agarwal SK, Sukhodolets MV, Obungu VH, Novotny EZ, Crabtree JS, Chandrasekharappa SC, Collins FS, Spiegel AM, Burns, AL, Marx SJ. The 32-kDa subunit of replication protein protein A interacts with menin, the product of the MEN1 tumor suppressor gene. Mol Cell Biol 23: 493-509, 2003.

Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, Agarwal SK, Sood R, Jones MP, Moses TY, Haven C, Petillo D, Leotlela PD, Harding B, Cameron D, Pannett AA, Höög A, Heath H III, James-Newton LA, Robinson B, Zarbo RJ, Cavaco BM, Wassif W, Perrier ND, Rosen IB, Kristoffersson U, Turnpenny PD, Farnebo L-O, Besser GM, Jackson CE, Morreau H, Trent JM, ThakkerRV, Marx SJ, Teh BT, Larsson C, Hobbs MR. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome. Nature Genetics, 32: 676-80, 2002.

Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein L, Cochran C, Skarulis MC, Spiegel AM, Libutti SK, Alexander HR, Chen CC, Chang RR, Chandrasekharappa SC, Collins FS. Hyperparathyroidism in hereditary syndromes: Special expressions and special managements. J Bone Min Res 17 (Suppl 2): N37-N43, 2002.

Marx SJ. Multiple endocrine neoplasia type 1. in Vogelstein B, Kinzler KW eds. The Genetic Basis of Human Cancer, second edition. McGraw Hill. New York, 2002. pp 475-500.

Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, Marx SJ. Familial isolated hyperparathyroidism: Clinical and genetic characteristics of thirty-six kindreds. Medicine 81: 1-26, 2002.

Brandi ML, Gagel RF, Angeli A, Bilezekian JP, Beck-Peccoz P, Bordi C, Conte-Delvox B, Falchetti A, Gheri RG, Libroia A, Lips CJM, Lombardi G, Mannelli M, Pacini F, Ponder BAJ, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA jr, Marx SJ. Guidelines for diagnosis and therapy of multiple endocrine neoplasia type 1 and type 2. J Clin Endocrinol Metab 86: 5658-71, 2001.

McKeeby JL, Li X, Zhuang Z, Vortmeyer AO, Huang S, Pirner M, Skarulis MC, James-Newton L, Marx SJ, Lubensky IA. Multiple leiomyomas of the esophagus and uterus in multiple endocrine neoplasia type 1. Am J Pathol 159: 1121-27, 2001

Crabtree JS, Scacheri PC, Ward JM, Garrett-Beal L, Emmert-Buck MR, Edgemon KA, Lorang D, Libutti SK, Chandrasekharappa SC, Marx SJ, Spiegel AM, Collins FS. A mouse model of MEN1 develops multiple endocrine tumors. Proc Nat Acad Sci USA 98: 1118-23, 2001.

Marx SJ. Hyperparathyroid and hypoparathyroid disorders. New Eng J Med 343: 1863-75, 2000. [Correction in New Eng J Med 344: 240, 2001]

Knapp JL, Heppner C, Hickman AB, Burns AL, Chandrasekharappa SC, Collins FS, Marx SJ, Spiegel AM, Agarwal SK. Identification and characterization of junD missense mutants that lack menin binding. Oncogene 19: 4706-12, 2000.

Kim YS, Burns AL, Goldsmith PK, Heppner C, Park SY, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ: Stable overexpession of MEN1 suppresses tumorigenictiy of RAS. Oncogene. 18:5936-5942, 1999.

Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins M, Park SY, Saggar S., Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, and Burns AL: Menin interacts with the AP1 transcription factor JunD and represses JunD activated transcription. Cell 96:143-152, 1999.

Heppner C, Kester MB, Agarwal SK, Debelenko LV, Emmert-Buck MR, Guru SC, Manickam P, Olufemi SE, Skarulis MC, Doppman JL, Alexander RH, Kim YS, Saggar SK, Lubensky IA, Zhuang Z, Liotta LA, Chandrasekharappa SC, Collins FS, Spiegel AM, Burns AL, Marx SJ: Somatic mutation of the MEN1 gene in parathyroid tumors. Nature Genetics 16: 375-378, 1997

Agarwal SK, Kester MB, Debelenko LV, Heppner C, Emmert-Buck MR Skarulis MC, Doppman JL, Kim YS, Lubensky IA, Zhuang Z, Green JS, Guru SC, Manickam P, Olufemi SE, Liotta LA, Chandrasekharappa SC, Collins FS, Spiegel AM, Burns AL, Marx SJ Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6: 1169-1175, 1997

Chandrasekharappa SC, Guru SC, Manickam P, Olufemi S-E, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weiseman J, Bogusky MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, Marx SJ: Positional cloning of the gene for multiple endocrine neoplasia type 1. Science 276: 404-407, 1997



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