Dorothy Teegarden

PULSe Contributor - not currently hosting students for laboratory rotations or recruiting students in the laboratory

Current Research Interests:

My research laboratory investigates mechanisms of disease progression and prevention of age-related diseases, particularly cancer. One area of focus is understanding the basic cellular mechanisms involved in regulating energy and lipid metabolism, including the roles that the enzyme pyruvate carboxylase (PC; in metastasis promotion) and vitamin D (in cancer prevention) play in the development of cancer and metastases. There is increasing recognition of the importance of the dysregulation of energy metabolism in cancer development. Although there is some evidence that the enzyme pyruvate carboxylase plays a role in cancer progression, particularly metastasis, little is known about the underlying mechanisms. Our studies are among the first to show that pyruvate carboxylase plays an essential role in fatty acid metabolism in metastatic cancer cells and is critical in the increased oxidative stress protection in cancer cells. We are also the first to show that pyruvate carboxylase is essential for breast cancer metastasis. These findings provide, for the first time, a mechanistic basis for the critical role of pyruvate carboxylase in cancer progression, particularly metastasis, and lay the foundation for understanding the metabolic shifts necessary to support metastasis. Substantial evidence suggests that vitamin D helps prevent the development of several cancers, including breast cancer. Our studies, which used appropriate cell models of cancer prevention, identified unique mechanisms by which 1,25 dihydroxyvitamin D inhibits processes essential to preventing cancer, including glucose and glutamine metabolism. Further, we showed that 1,25 dihydroxyvitamin D inhibits metastasis of breast epithelial cells, using a unique 3D cell culture model of breast to bone metastasis.

Selected Publications:

Larrick B, Kim K-H, Donkin SD, Teegarden D. (2018) 1,25-Dihydroxyvitamin D regulates lipid metabolism and glucose utilization in differentiated 3T3-L1 adipocytes. Nutr Res 58:72-83. PMID: 30340817

Shinde A, Wilmanski T, Chen H, Teegarden D, Wendt M. (2018) Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer. Breast Cancer Res. 13;20(1):76. doi: 10.1186/s13058-018-1008-9. PMID: 3000560

Wilmanski T, Zhou X, Zheng W, Shinde A, Donkin SS, Wendt M, Burgess JR, Teegarden D. (2017) Inhibition of pyruvate carboxylase by 1α,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression. Cancer Lett. 2017 Oct 9;411:171-181. PMID: 29024812.

Wilmanski T, Buhman K, Donkin SS, Burgess JR, Teegarden D. (2016) 1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase. J Nutr Biochem 40:194-200.

Wilmanski T, Barnard A, Parikh MR, Kirshner J, Buhman K, Burgess J, Teegarden D. (2016) 1α,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis. Nutr Cancer. 68(7):1202-9. PMID: 27552186

Zhou X, Zheng W, Nagana Gowda GA, Raftery D, Donkin SS, Bequette B, Teegarden D. (2016) J Steroid Biochem Mol Biol. 1,25-Dihydroxyvitamin D inhibits glutamine metabolism in Harvey-ras transformed MCF10A human breast epithelial cell. J Steroid Biochem Mol Biol. 163:147-56. PMID: 27154413

Zheng W, Tayyari F, Gowda GA, Raftery D, McLamore ES, Porterfield DM, Donkin SS, Bequette B, Teegarden D. (2015) Altered glucose metabolism in Harvey-ras transformed MCF10A cells. Molecular Carcinogenesis Feb; 54(2):111-20. PMID: 24000146

Zheng W, Tayyari F, Gowda GA, Raftery D, McLamore ES, Shi J, Porterfield M, Donkin SS, Bequette B, Teegarden D. (2013) 1, 25 Dihydroxyvitamin D Regulation of Glucose Metabolism in Harvey-ras Transformed MCF10A Human Breast Epithelial Cells. J Ster Biochem Mol Biol 138:81-89. PMID: 23619337.

Li J, Byrne ME, Chang E, Jiang Y, Donkin SS, Buhman KK, Burgess JR and Teegarden D. (2008) 1±,25-dihydroxyvitamin D hydroxylase in adipocytes, J Steroid Biochem 112:122-126..

Chang E, Donkin SS, and Teegarden D (2009) Parathyroid Hormone Suppresses Insulin Signaling in Adipocytes. Mol Cell Endo, in press.

Siddiqui SMK, Chang E, Li J, Burlage C, Zou M, Buhman KK, Koser S, Donkin SS and Teegarden D. (2008) Dietary intervention with vitamin D, calcium and whey protein reduced fat mass and increased lean mass in rats. Nutrition Res 28:783-790.

Taber L, Adams LS, D. Teegarden. Mechanisms of nuclear vitamin D receptor resistance Harvey-ras transfected cells. J Nutr Biochem, in press.

Li J, Fleet JC, and D. Teegarden. Activation of rapid signaling pathways does not contribute to 1a,25-dihydroxyvitamin D3-induced growth inhibition of mouse prostate epithelial progenitor cells. J Cellular Biochem, in press.