Youngsook Lee

Associate Professor

youngsooklee@wisc.edu

Phone: (608) 265-6352

RESEARCH INTERESTS - Transcriptional control of normal cardiovascular development and function

 

Address: 4431 WIMR II – 1111 Highland Ave. – Madison, WI 53705 

PubMed

Education

B.S., Ewha Women’s University, Seoul, Korea
M.S., Seoul National University, Seoul, Korea
Ph.D., University of Wisconsin, Madison
Postdoctoral Research, Harvard Medical School, Boston

Research

Malformation of the cardiovascular system is the most common form of human birth defect and cardiovascular disease is the leading cause of mortality. However, the molecular mechanisms that cause these heart diseases remain poorly understood.

The long-term goal of my laboratory is to advance our understanding of the transcriptional controls that guide cardiovascular differentiation / development and maintenance of normal cardiac function. The focus of our current research is to identify novel cellular and molecular mechanisms that lead to normal cardiac morphogenesis and function. For this, we are investigating molecular mechanisms that regulate cardiac-specific gene expression in vitro and role of transcription factors in cardiovascular development in vivo by generating transgenic mice. For example, we are studying molecular functions of the cardiac-restricted homeobox protein Nkx2.5, zinc finger protein GATA4, muscle-specific factor MEF2, and the nuclear factor Jumonji in regulating target genes and guiding normal cardiovascular development.

Embryonic stem cells are pluripotent cells. One goal of stem cell research is the development of specialized cells such as heart muscle cells. The directed differentiation of embryonic stem cells is then vital to the ultimate use of such cells in the development of new therapies. We are currently developing methods to isolate and enrich embryonic stem cell-derived cardiomyocytes.

Representative Publications

  • Cervantes S, Fontcuberta-PiSunyer M, Servitja JM, Fernandez-Ruiz R, García A, Sanchez L, Lee YS, Gomis R, Gasa R. Late-stage differentiation of embryonic pancreatic beta-cells requires Jarid2. Sci Rep. 2017 Sep 14;7(1):11643.
  • Brody MJ, Lee Y. The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy. Front Physiol. 2016 Aug 3;7:337. Review.
  • Burger NB, Haak MC, Kok E, de Groot CJ, Shou W, Scambler PJ, Lee Y, Cho E, Christoffels VM, Bekker MN. (2016) Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Early Hum Dev. 2016 101:39-48.
  • Brody, M.J., Feng, L., Grimes, A.C., Hacker T.A., Olson, T.M., Kamp, T.J., Balijepalli, R.C., and Lee, Y. (2016) LRRC10 is required to maintain cardiac function in response to pressure overload. American J of Physiology, 310:H269-278. PMC4747898
  • Chang, Y.-H., Ye, L., Cai, W., Lee Y., Guner, H., Lee, Y., Kamp, T.J., Zhang, J., and Ge, Y. (2015) Quantitative proteomics reveals differential regulation of protein expression in recipient myocardium after tri-lineage cardiovascular cell transplantation. Proteomics, 15:2560-2567. PMC4690722
  • Pereira, R.M., Martinez, G.J., Engel, I., Cruz-Guilloty, F., Barboza, B.A., Tsagaratou, A., Lio, C.W., Berg, L.J., Lee, Y., Kronenberg, M., Bandukwala, H.S., and Rao, A. (2014) Jarid2 is induced by TCR signalling and controls iNKT cell maturation. Nature Communications, 5:4540-4553. PMC4314221
  • Brody, M.J., Cho, E.J., Mysliwiec, M.R., Kim T.-G., Carlson C.D., Lee, K.-H., and Lee, Y. (2013) Lrrc10 is a novel cardiac-specific target gene of Nkx2.5 and GATA4. J. Mol Cell Cardiology 62:237-246. PMC3940241
  • Brody, M.J., Hacker T., Patel, J.R., Li, F., Sadoshima, J., Tevosian, S.G., Balijepalli, R.C., Moss, R.L., and Lee, Y. (2012) Ablation of the cardiac-specific gene Leuicine-Rich repeat Containing 10 (Lrrc10) results in dilated cardiomyopathy. PLoS One, 7 (12) e51621. PMC3517560
  • Johnson, K.D., Hsu, A.P., Ryu M.-J., Boyer, M.E., Keles, S., Zhang, J., Lee, Y., Holland, S.M., and Bresnick, E.H. (2012) Cis-element mutated in a GATA2-dependent immunodeficiency syndrome governs hematopoiesis and vascular integrity. J. Clin. Invest. 122:3692-3704. . PMC3461907
  • Mysliwiec, M.R., Carlson C.D., Tietjen, J., Hung, H., Ansari A.Z., and Lee, Y. (2012) Jarid2 (JUMONJI, AT rich interactive domain 2) regulates Notch1 expression via histone modification in the developing heart. J. Biol. Chem. 287:1235-1241. PMC3244653
  • Mejetta, S., Morey, L., Pascual, G., Kuebler B., Mysliwiec M.R., Lee, Y., Shiekhattar R., Croce L.D., Benitah, S.A. (2011) Jarid2 regulates mouse epidermal stem cell activation and differentiation.EMBO J. 30:3635-3646, . PMC3181486
  • Mysliwiec, M.R., Bresnick, E.H., and Lee, Y. (2011) Endothelial Jarid2/Jumonji is required for normal cardiac development and proper Notch1 expression. J. Biol. Chem. 286:17193-17204. PMC 3089562
  • Zhang Z, Jones A, Sun CW, Li C, Chang CW, Joo HY, Dai Q, Mysliwiec MR, Wu LC, Guo Y, Yang W, Liu K, Pawlik KM, Erdjument-Bromage H, Tempst P, Lee Y, Min J, Townes TM, Wang H. (2011) PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming. Stem Cells. 29:229-40.PMC3711030.
  • Lee, Y. (2010) To proliferate or not to proliferate. Cardiovascular Research. Editorial. 86:347-348
  • Carlson C.D., Warren, C.L., Hauschild, K.E., Ozers, M.S., Qadir, N., Lee, Y., Bhimsaria, D., and Ansari, A.Z. (2010) Specificity Landscapes of natural and engineered DNA binding molecules predict biological function. Proc Natl Acad Sci USA 107:4544-4549. PMC2842033
  • Shen, X., Kim, W., Fujiwara, Y., Liu Y., Mysliwiec, M.R., Yuan G-C., Lee, Y., and Orkin, S.H. (2009) Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell 139:1303-1314
  • Lin, B.C., Sullivan R., Lee, Y., Moran, S., Glover, E., and Bradfield, C.A. (2007) Deletion of aryl hydrocarbon receptor associated protein 9 leads to cardiac malformation and embryonic lethality. J. Biol. Chem. 282:35924-32.
  • Kim, K.-H., Antkiewicz, D.S., Yan, L., Eliceiri, K.W., Heideman, W., Peterson, R.E., and Lee, Y. (2007) Lrrc10 is required for early heart development and function in zebrafish. Developmental Biology. 308:494-506.
  • Kim, K.-H., Kim T.-G., Micales, B., Lyons, G.E., and Lee, Y. (2007) Dynamic expression patterns of Leucine Rich Repeat Containing Protein 10 in the heart. Developmental Dynamics, 236:2225-2234.
  • Mysliwiec, M.R., Kim, T.-G., and Lee, Y. Characterization of Zinc Finger Protein 496 that interacts with Jumonji/jarid2. FEBS Letters, 581(14):2633-2640, 2007
  • Mysliwiec, M.R., Chen, J., Powers, P.A., Bartley, C.R., Schneider, M.D., and Lee, Y. (2006) Generation of a Conditional Null Allele of Jumonji. Genesis, 44(9):407-411.
  • Kim, T.-G., Jung, J., Mysliwiec, M.R., and Kang, S., and Lee, Y. (2005) JUMONJI represses a-cardiac myosin heavy chain expression via inhibiting MEF2 activity. Biochem. Biophys. Res. Commun. 329:544-553.
  • Jung, J., Kim, T.-G., Lyons, G.E., Kim, H.R.C., and Lee, Y. (2005) Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. J. Biological Chemistry, 280:30916-30923.