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Faculty Andrew Arnold
Professor of Medicine and Genetics & Developmental Biology
Director, Center for Molecular Medicine
Murray-Heilig Chair in Molecular Medicine
molecularmedicine@uchc.edu
The most longstanding interest of our laboratory has been in the
molecular genetic underpinnings of tumors of the endocrine glands. It
was in the context of a search for a parathyroid tumor oncogene lying
adjacent to a clonal chromosomal breakpoint that we discovered cyclin D1
(PRAD1). Cyclin D1 has proven to play a key role in cell cycle
regulation, and has emerged as a major human oncogene, important in
multiple types of tumors including breast cancer and B-cell lymphoma. We
are currently pursuing a number of approaches, including the use of
transgenic mouse models, to learn more about the precise mechanisms by
which cyclin D1 exerts its oncogenic effects. In addition to the cyclin
D1 work, we are continuing a major initiative seeking additional genes
that contribute to endocrine neoplasia, and recently identified HRPT2
gene mutations as a major cause of parathyorid cancer. Furthermore, we
are interested in clarifying the link between abnormal proliferation and
hormonal function, a fundamental problem in endocrine tumorigenesis, and
have developed a transgenic mouse model of hyperparathyroidism which
provides an appealing system in which to pursue these questions.
Visit the Center For Molecular Medicine webpage:
http://cmm.uchc.edu/index.html
Selected Publications:
Mallya SM, Gallagher JJ, Arnold A. Analysis of microsatellite
instability in sporadic parathyroid adenomas. J Clin Endocrinol Metab
2003; 88:1248-1251.
Costa J, Shattuck TM, Imanishi Y, Palanisamy N, Gaz RD, Shoback D,
Clark OH, Monchik JM, Wierman ME, Hollenberg A, Tojo K, Chaganti RSK,
Arnold, A. Mutational analyses of connexin 26, connexin 30 and connexin
46 as candidate tumor suppressor genes in parathyroid carcinoma. J
Endocr Genet 2003; 3:57-62
Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D,
Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C,
Arnold A. Somatic and germ-line mutations of the HRPT2 gene in sporadic
parathyroid carcinoma. N Engl J Med 2003 Oct 30; 349(18):1722-9.
Imanishi Y, Tahara H, Palanisamy N, Spitalny S, Salusky IB, Goodman
W, Brandi ML, Drueke TB, Sarfati E, Urena P, Chaganti RSK, Arnold A.
Clonal chromosomal defects in the molecular pathogenesis of refractory
hyperparathyroidism of uremia. J Amer Soc Nephrol 2002; 13:1490-1498.
Imanishi Y, Hall C, Sablosky M, Brown EM, Arnold A. New method for in
vivo analysis of parathyroid hormone-calcium setpoint in mice. J Bone
Miner Res 2002; 17:1656-1661.
Shattuck TM, Costa J, Bernstein M, Jensen RT, Chung DC, Arnold A.
Mutational analysis of Smad3, a candidate tumor suppressor implicated in
transforming growth factor-B and memin pathways, in parathyroid adenomas
and enteropancreatic endocrine tumors. J Clin Endocrinol Metab 2002;
87:3911-3914.
Imanishi Y, Hosokawa Y, Yoshimoto K, Schipani E, Mallya S,
Papanikolaou A, Kifor O, Tokura T, Sablosky M, Ledgard F, Gronowicz G,
Wang TC, Schmidt EV, Hall C, Brown EM, Bronson R, Arnold A. Primary
hyperparathyroidism caused by parathyroid-targeted overexpression of
cyclin D1 in transgenic mice. J Clin Invest 2001; 107:1093-1102.
Hosokawa Y, Papanikolaou A, Cardiff RD, Yoshimoto K, Bernstein M,
Wang TC, Schmidt EV, Arnold A. In vivo analysis of mammary and
non-mammary tumorigenesis in MMTV-cyclin D1transgenic mice deficient in
p53. Transgenic Res 2001; 10:471-478.
Brown SB, Brierley TT, Palanisamy N, Salusky IB, Goodman W, Brandi
ML, Drueke TB, Sarfati E, Urena P, Chaganti RSK, Pike JW, Arnold A.
Vitamin D receptor as a candidate tumor suppressor gene in severe
hyperparathyroidism of uremia. J Clin Endocrinol Metab 2000; 85:868-72. |
