Department of Biology and Biochemistry
Office: Science & Engineering Research Center, 3021
Contact: firstname.lastname@example.org - (713) 743-7451
Education: Ph.D., University of Tokyo
Dr. Michihisa Umetani’s long-term area of interest is to understand the role of cholesterol metabolites, or oxysterols, in cardiovascular and related diseases, such as atherosclerosis, cancer and metabolic diseases. Previously, his lab discovered that the most abundantly circulating oxysterol 27-hydroxycholesterol (27HC) directly binds to estrogen receptor (ER) and alters the ER function in a tissue-specific manner. Importantly, 27HC is the first identified endogenously produced selective ER modulator (SERM), and has an adverse impact on the cardiovascular protection afforded by estrogen. 27HC also promotes breast tumor progression and decreases bone mineral density through the modification of ER activity.
Since serum 27HC levels closely correlate with circulating cholesterol levels, diet-induced condition that increases cholesterol levels may also alter the estrogen-mediated homeostasis through 27HC. In addition, recently the lab found that Liver X Receptor (LXR), which also belongs to the nuclear receptor superfamily and has oxysterols as its ligands, has a novel function in the vascular endothelial cells through non-transcriptional (non-nuclear) actions that are mediated by crosstalk between LXR beta and ER alpha.
The Umetani Lab is investigating the impacts of oxysterols on the physiological function regulated by ER using molecular biology, cell culture and in vivo mouse models. Through these studies, he hopes to develop novel therapeutic approaches that target diet-induced vascular dysfunction.
- Umetani M. (2016) Re-adopting classical nuclear receptors by cholesterol metabolites. J. Steroid Biochem. Mol. Biol. 157, 20-6.
- Lee WR, Ishikawa T, and Umetani M*. (2014) The interaction between Metabolism, Cancer, and Cardiovascular disease, connected by 27-Hydroxycholesterol. Clin. Lipidol. 9, 617-24.
- Umetani M, Ghosh P, Ishikawa T, Umetani J, Ahmed M, Mineo C, Shaul PW. (2014) The Cholesterol Metabolite 27-Hydroxycholesterol Promotes Atherosclerosis via Proinflammatory Processes Mediated by Estrogen Receptor Alpha. Cell Metabolism. 20, 172-82.
- Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, Carver NJ, Pillai RV, Sullivan PM, Sondhi V, Umetani M, Geradts J and McDonnell DP. (2013) 27- Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology. Science. 342, 1094-8.
- Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald JG, Yuhanna IS, Thompson B, Girard L, Mineo C, Brekken RA, Umetani M, Euhus DM, Xie Y, and Shaul PW. (2013) 27- Hydroxycholesterol Promotes Cell-autonomous ER-positive Breast Cancer Growth. Cell Reports. 5, 637-45.
- Ishikawa T, Yuhanna IS, Umetani J, Lee WR, Korach KS, Shaul PW, and Umetani M*. (2013) LXRb/estrogen receptor-asignaling in lipid rafts preserves endothelial integrity. J. Clin. Invest. 123, 3488-97.
- Umetani M* and Shaul PW*. (2011) 27-Hydroxycholesterol: the First Identified Endogenous SERM. Trends Endocrinol. Metab. 22, 130-5. (* corresponding authors)
- Nelson ER, DuSell CD, Wang X, Howe MK, Evans G, Michalek RD, Umetani M, Rathmell JC, Khosla S, Gesty-Palmer D, McDonnell DP. (2011) The oxysterol, 27- hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors. Endocrinology 152, 4691-705.
- Li T, Holmstrom SR, Kir S, Umetani M, Schmidt DR, Kliewer SA, and Mangelsdorf DJ. (2011) The G Protein-Coupled Bile Acid Receptor, TGR5, Stimulates Gallbradder Filling. Mol. Endocrinol. 25, 1066-1071.
- Dusell CD, Nelson, ER, Wang X, Abdo J, Mödder UI, Umetani M, Gesty-Palmer D, Javitt NB, Khosla S, and McDonnell DP. (2010) The Endogenous Selective Estrogen Receptor Modulator 27-Hydroxycholesterol Is a Negative Regulator of Bone Homeostasis. Endocrinol. 151, 3675-3685.
- Chambliss KL, Wu Q, Oltmann S, Konaniah ES, Umetani M, Korach KL, Thomas GD, Mineo C, Yuhanna YS, Kim SH, Madak-Erdogan Z, Maggi A, Dineen SP, Roland CL, Hui DY, Brekken RA, Katzenellenbogen JA, Katzenellenbogen BS, and Shaul PW. (2010) Nongenomic Estrogen Receptor Alpha Signaling Promotes Cardiovascular Protection but not Uterine or Breast Cancer Growth in Mice. J. Clin. Invest. 120, 2319- 2330.
- Dusell CD, Umetani M, Shaul PW, Mangelsdorf DJ, and McDonnell DP. (2008) 27- Hydroxycholesterol is an endogenous Selective Estrogen Receptor Modulator (SERM). Mol. Endocrinol. 22, 65-77.
- Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, and Mangelsdorf DJ. (2007) 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat. Med. 13, 1185-1192.
- Choi M, Moschetta A, Bookout AL, Peng L, Umetani M, Holmstrom SR, Suino-Powell K, Xu HE, Richardson JA, Gerard RD, Mangelsdorf DJ, and Kliewer SA. (2006) Identification of a hormonal basis for gallbladder filling. Nat. Med. 12, 1253-1255.
- Goodwin BJ, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, Leitersdorf E, Mangelsdorf DJ, Kliewer SA, and Repa JJ. (2003) Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic receptor PXR. Proc. Natl. Acad. Sci. USA 100, 223-228.
Honors and Awards:
2002 Uehara Memorial Fellowship
2007 2nd place, 7th Annual Cardiovascular Research Symposium, UT Southwestern Medical Center
2009 UT Southwestern O’Brien Kidney Research Center Pilot & Feasibility Award
2010 Early Career Investigator Award, Kern Aspen Lipid Conference
2010 Travel Award for Young Investigators, American Heart Association
2011 Junior Faculty Award, American Diabetes Association
2015 BeHEARD Challenge 2015 Technology Award
Organizations, Outreach, Boards, Memberships:
Member, American Heart Association
Member, American Diabetes Association
Editorial Board, Frontiers in Cancer Endocrinology