Research
Contribution to Science
1. Defined the genetic and epigenetic roles played by a membrane-type collagenase in obesity, diabetes, and atherosclerosis.
a. Chun TH, Inoue M, Morisaki H, Yamanaka I, Miyamoto Y, Okamura T, Sato-Kusubata K, Weiss SJ. Genetic link between obesity and MMP14-dependent adipogenic collagen turnover. Diabetes. 2010 Oct;59(10):2484-94. PMID: 20660624; PMCID: PMC3279534.
b. Sato-Kusubata K, Jiang Y, Ueno Y, Chun TH. Adipogenic histone mark regulation by matrix metalloproteinase 14 in collagen-rich microenvironments. Mol Endocrinol. 2011 May;25(5):745-53. PMID: 21436261; PMCID: PMC3082327.
c. Chun TH, Inoue M. 3-D adipocyte differentiation and peri-adipocyte collagen turnover. Methods Enzymol. 2014;538:15-34. PMID: 24529431.
d. Barnes RH, Akama T, Ohman MK, Woo MS, Bahr J, Weiss SJ, Eitzman DT, Chun TH. Membrane-tethered metalloproteinase expressed by vascular smooth muscle cells limits the progression of proliferative atherosclerotic lesions. Journal Am Heart Assoc. 2017;6:e003693. PMC5586255.
2. Discovered the significance of adipose-derived circulating ECM protein in causing muscle insulin resistance and fibrosis in mice and humans
a. Inoue M, Jiang Y, Barnes RH 2nd, Tokunaga M, Martinez-Santibañez G, Geletka L, Lumeng CN, Buchner DA, Chun TH. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice. Endocrinology. 2013 Dec;154(12):4548-59. PMID: 24140711; PMCID: PMC3836064.
b. Matsuo Y, Tanaka M, Sasaki Y, Yamakage H, Muranaka K, Hata H, Ikai I, Shimatsu A, Inoue M, Chun TH*, Satoh-Asahara N*. (*Co-corresponding authors). Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome. Metabolism. 2015;64:1490-9. PMID: 26298466 PMCID: PMC4936918
c. Buras ED, Converso-Baran K, Davis CS, Akama T, Fumihito H, Michele DE, Brooks SV, Chun
TH. Fibro-adipogenic remodeling of the diaphragm in obesity-associated respiratory
dysfunction. Diabetes in press (2018). PMID: 30361289 DOI: 10.2337/db18-0209
3. Newly identified the fat depot-dependent gene expression and ECM remodeling of adipose-derived stem cells (ASCs).
a. Tokunaga M, Inoue M, Jiang Y, Barnes RH 2nd, Buchner DA, Chun TH. Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose-derived stem cells. Matrix Biol. 2014;36:28-38. PubMed PMID: 24726953; PubMed Central PMCID: PMC4127346.
b. Barnes RH 2nd, Chun TH. Immunomagnetic Separation of Fat Depot-specific Sca1high Adipose- derived Stem Cells (ASCs). J Vis Exp. 2016. PMID: 27583550 PMCID: PMC5010008
c. Akama T and Chun TH. "Transcription factor 21 (Tcf21) promotes proinflammatory interleukin 6
expression and extracellular matrix remodeling in visceral adipose stem cells" J Biol Chem. Epub 2018 Mar 14. PubMed PMID: 29540474; PMCID: PMC5925812.
4. Developed 3-D adipose organoid models for human disease modeling
a. Chun TH, Hotary KB, Sabeh F, Saltiel AR, Allen ED, Weiss SJ. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell. 2006;125:577-91. PMID: 16678100.
b. Moraes C, Labuz JM, Leung BM, Inoue M, Chun TH, Takayama S. On being the right size: scaling effects in designing a human-on-a-chip. Integr Biol (Camb). 2013:1149-61. PMID: 23925524; PMCID: PMC3787867.
c. Chun TH, Inoue M. 3-D adipocyte differentiation and peri-adipocyte collagen turnover. Methods Enzymol. 2014;538:15-34. PMID: 24529431.
d. Akama T, Leung BM, Labuz J, Takayama S, Chun TH. Designing 3-d adipospheres for quantitative metabolic study. Methods Mol Biol. 2017;1566:177-183
e. Hikage F, Atkins S, Kahana A, Smith TJ, Chun TH. HIF2A-LOX pathway promotes fibrotic tissue remodeling in thyroid-associated orbitopathy. Endocrinology (2018) PMID: 30388216 DOI: 10.1210/en.2018-00272.
5. Discovered a new role for the exocyst complex in facilitating free fatty acid uptake by adipocytes.
a. Inoue M, Akama T, Jiang Y, Chun TH. The exocyst complex regulates free fatty acid uptake by adipocytes. PLoS One. 2015;10(3):e0120289. PMID: 25768116; PMCID: PMC4359155.
There are no small problems ; those which seem so are large ones not properly understood. To observe without thinking is as bad as to think without observing, and no fact need ever be considered too insignificant, for the minutiae of today may be important truths tomorrow. -Ramon y. Cajal