Toland, Amanda

Amanda Toland, Ph.D.

Assistant Professor
Primary Appointment
Department of Molecular Virology, Immunology and Medical Genetics Human Cancer Genetics Program

For More Information:
Please visit Human Cancer Genetics

Contact Information:

Office phone: 614-247-8185

Lab phone: 614-247-7309

Fax number: 614-688-8675

Address:
 Office - 998 Biomedical Research Tower, 
 Lab -      950 Biomedical Research Tower,
                460 W. 12th Ave, Columbus, OH 43210

E-mail: amanda.toland@osumc.edu

Research Interest:
Identification of cancer susceptibility genes

Research Summary:
Dr. Toland's laboratory is interested in the identification of human cancer susceptibility genes with a particular focus on identifying combinations of susceptibility genes that work together to influence an individual's risk of developing cancer.   Because traditional genetic methods for the identification of low risk genes are less then ideal, the laboratory employs an integrated approach using mouse models, tumor imbalance data, tumor expression data, and human population studies to address this problem. 

Using an integrated mouse-human approach, we identified a variant in Aurora-A (STK15) that modestly increases risk of developing breast, ovarian, prostate, non-melanoma skin, lung, esophageal, and colon cancers.  From our mouse models, we know that a gene mapping to the Aurora-A locus interacts with two other genes.  When a mouse carries susceptibility alleles at all three loci, the risk of developing cancer is 8-9 times higher then carrying susceptibility alleles at none of these loci.  A major focus of the laboratory is to identify the gene at one of these loci, Skts5, using our combined mouse/human approach.  Once a top candidate gene has been identified, we will study the gene using cell culture, mouse models and a variety of other techniques to determine the mechanism underlying the cancer risk and why the combination with Aurora-A is important.

Other projects in the lab are the identification of genetic risk determinants of squamous cell carcinoma of the skin in individuals who have had organ transplants and characterization of BRCA1 and BRCA2 variants of uncertain significance.

Selected Publications:
Watkins, WS, O'Connell, P, Stevens, J, Culver, M, Ewart, A and Jorde LB. A Bgl II RFLP near the human neurofibromatosis type 1 (NF1) gene. Nuc. Acid. Res. 19: 6662, 1991.

Ewart, AK, Morris, CA, Ensing, G, Loker, J, Moore, C, Leppert, M, and Keating, MT.  A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.  Proc. Natl. Acad. Sci., USA 90:3226-3230, 1993.

Curran, ME, Atkinson, DL, Ewart, AK, Morris, CA, Leppert, MF, and Keating, MT. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell. 73: 159-168, 1993.

Ewart, AK, Morris, CM, Atkinson, DA, Jin, W. Sternes, K., Spallone, P, Stock, D.A., Leppert, M, and Keating, MT.  Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.  Nature Genet.  5: 11-16, 1993.

Ewart, AK, Jin, W, Atkinson, DA, Morris, CA, and Keating, MT.  Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.  J. Clin. Invest. 93: 1071-1077, 1994.      

Lowery, MC, Morris, CA, Ewart, AK, Brothman, LJ, Zhu, XL, Leonard, C., Carey, J., Keating, M., and Brothman, A.  Strong correlation of elastin deletions detected by fluorescence in situ hybridization (FISH) with Williams syndrome:  Evaluation of 235 patients. Am. J. Hum. Genet. 57: 49-53, 1995.

Frangiskakis, JM, Ewart, AK, Morris, CA, Mervis, CB, Bertrand, J, Robinson, BF, Klein, BP, Ensing, GJ, Everett, LA, Green, ED, Atkinson, DL, Odelberg, SJ, and Keating, M. Limk-kinase hemizygosity implicated in impaired visuospatial constructive cognition. Cell. 56: 59-69, 1996.  

Li, D., Toland AE,  Boak, BB, Atkinson, DL, Ensing, GE, Morris, CA, and Keating, MT. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.  Hum. Mol. Genet. 6: 1021-1026, 1997.

Ewart-Toland, A, Enns, GE, Cox, VA, ChandraMohan, G, Rosenthal, P, and Golabi, M. Severe congenital anomalies requiring transplantation in children with kabuki syndrome.  Am. J. Med. Genet. 80: 362-367, 1998.

Mounzih, K, Qiu, J, Ewart-Toland, A, and Chehab, FF.  Leptin is not necessary for gestation and parturition but regulates maternal nutrition via a leptin resistance state.  Endocrinology, 139: 5259-5262, 1998.

Ewart-Toland, A, Mounzih, K, Qiu, J, and Chehab, FF.  Effect of genetic background on the reproduction of leptin-deficient mice. Endocrinology,140: 732-738, 1999.

Ewart-Toland, A, Yankowitz, J, Winder, A, Cox, VA, Aylsworth, AS, and Golabi, M.  Oculoauriculovertebral abnormalities in children of diabetic mothers. Am J. Med. Genet.  90: 303-309 (2000).

Qiu, J, Ogus, S, Mounzih, K, Ewart-Toland, A and Chehab, FF. Leptin-deficient mice backcrossed to the BALB/cJ genetic background have reduced adiposity, enhanced fertility, normal body temperature, and severe diabetes. Endocrinology. 142:3421-3425, 2001.

Chehab, FF, Qiu, J, Mounzih, K, Ewart-Toland, A, and Ogus, S. Leptin and reproduction. Nutr. Rev. 60:S39-46, 2002.

Ewart-Toland, A, Briassouli, P, de Koning, JP, Mao, J-H, Yuan, J, Chan, F., MacCarthy-Morrogh, L, Ponder, BAJ, Nagase, H, Burn, J, Ball, S, Almeida, M, Linardopoulos, S, and Balmain A. Identification of Stk6/STK15 as a candidate modifier of cancer risk in mouse and man. Nat. Genet. 34:403-412, 2003

Ewart-Toland, A, Chan, J, Yuan, J, Balmain, A. and Ma, J. TGFB-1 polymorphisms may be associated with late stage prostate cancer.  Cancer Epidemiol. Biomarkers Prev. 13: 759-764, 2004.

Dai,Q,  Cai, Q-Y, Shu, X-O, Ewart-Toland, A, Wen, W-Q, Balmain, A, Gao, Y-T, and Zheng, W. Synergistic effects of STK15 gene polymorphisms and endogenous estrogen exposure in the risk of breast cancer. Cancer Epidemiol, Biomarkers Prev. 13: 2065-2070, 2004.

Ewart-Toland, A and Balmain, A.  The Genetics of Cancer Susceptibility: From Mouse to Man. Tox. Pathol. 32(Suppl. 1): 26-30, 2004.

Ewart-Toland, A, Dai, Q, Gao, Y-T, Nagase, H, Dunlop, MG, Farrington, SM, Barnetson, RA, Anton-Culver, H, Peel, D, Ziogas, A, Lin, D, Miao, X, Sun, T, Ostrander, EA, Stanford, JL, Langlois, M, Chan, JM, Yuan, J, Harris, CC, Bowman, ED, Clayman, GL, Lippman, SM, Lee, JJ, and Balmain, A. Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types. Carcinogenesis, 26: 1368-1373, 2005.