East Carolina University. Tomorrow starts here.®
 
Department of Internal Medicine
Division of Hematology/Oncology


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Myon-Hee Lee, PhD                                                    Lee-Myon-Hee-web_1                                        
Assistant Professor
Division of Hematology/Oncology
600 Moye Blvd., Brody 3E127
Greenville, NC 27834
Tele: 252.744.3134
Fax:  252.744.3418

email: leemy@ecu.edu

  

 

Current Research Interests:

Stem cells have the ability to reproduce (i.e. self-renewal) and to give rise to specialized cells (i.e. differentiation).  Adult stem cells function as a reservoir for the replenishment of normal tissues and repair of damaged tissues.  It is clear that genetic networks control the balance between self-renewal and differentiation, and that misregulation of these networks can result in overproliferation of adult stem cells and cancer.

For several years, a increasing evidence supports the theory of cancer stem cells (CSCs) that tumor cells are heterogeneous containing rare tumor initiating cells (called by CSCs) and abundant non-tumor initiating cells.  Furthermore, it has been proven that CSCs are similar to the stem cells in many aspects and exist in multiple cancer cells such as acute and chronic myeloid leukemia, breast cancer, and lung cancer.  Therefore, specific therapies targeted at CSCs must be considered to increase the efficiency and safety of cancer treatment.  


 The long-term objective of my laboratory is to unravel molecular mechanisms of cell fate reprogramming in vivo.  Specifically, we focus on how stem cell regulators and small molecules control cell fate reprogramming in vivo and extend it by application of our findings to cancer stem cells (CSCs).  We use the nematode Caenorhabditis elegans (C. elegans) as a model system to study in vivo cell fate reprogramming.  In C. elegans, germline stem cells (GSCs) persist throughout adulthood and replenish the germline with thousands of differentiated gametes.  Importantly, a core network of conserved genes controls the balance between GSC renewal and differentiation.  More importantly, some of conserved RNA regulators (e.g. STAR/KH domain protein GLD-1) have been implicated in the regulation of stem cell (or CSC) self-renewal and cell fate reprogramming in the C. elegans germ line.  Therefore, C. elegans germline provides an attractive system for studying the reprogramming of CSCs.  

Our research plans include: (1) a focused analysis of the molecular mechanism of in vivo cell fate reprogramming, particularly dedifferentiation and trans-differentiation; (2) Identification and characterization of genetic regulators that contribute to reprogramming of stem cells (or CSCs) using a genetic/RNAi based-screening approach; (3) High-throughput screening of small molecules that induce cell fate reprogramming in C. elegans; (4) and the application of small molecule reprogramming in human disease models (e.g. leukemia).  Notably, the C. elegans signaling pathways and genetic factors we plan to investigate are conserved throughout animal evolution.  Thus, our work will provide mechanistic insight into the reprogramming process in humans and aid research into the prevention of human diseases, including cancers.

Selected Publications:

Peer reviewed papers

1.Clint, M.*, Lee, M.H.*, and Kimble J. Chemical reprogramming of germ cell fate induces functional oocytes in spermatogenic C. elegans adults. Nature Chemical Biology 6(2):102-4. *These authors contributed equally to this work.

2. Nykamp, K., Lee, M.H., and Kimble, J. (2008) C. elegans La related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis. RNA 14(8):1550-7. Internal Medicine (Hem/Onc) PI: Myon-Hee Lee

3. Lee, M.H., Hook, B., Pan, G., Kershner, A., Merritt, C., Seydoux, G., Thomson, J., Wickens, M., and Kimble J. (2007) Conserved Regulation of MAP Kinase Expression
by PUF RNA-Binding Proteins. PLoS Genet. 3(12):e233.

4. Lee, M.H., Hook, B., Lamont, L.B., Wickens, M., and Kimble, J. (2006) LIP-1 phosphatase controls the extent of germline proliferation in C. elegans. EMBO J. 25: 88-96.

5. Lee, M.H., Han, S.M., Han, J.W., Kim, Y.M., Ahnn, J., and Koo, H.S. (2003). Caenorhabditis elegans dna-2 is involved in DNA repair and is essential for germ-line
d
evelopment. FEBS Lett. 555:250-256.

6. Jeong, Y.S., Kang, Y., Lim, K.H., Lee, M.H., Lee, J., and Koo, H.S. (2003). Deficiency of Caenorhabditis elegans RecQ5 homologue reduces life span and increases sensitivity to onizingradiation. DNA Repair (Amst) 2:1309-1319.

7. Lee, K.H., Lee, M.H., Lee, T.H., Han, J.W., Park, Y.J., Ahnn, J., Seo, Y.S., and Koo, H.S. (2003) Dna2 Requirement for Normal Reproduction of Caenorhabditis elegans Is Temperature-dependent. Mol Cells 15(1):81-86.

8. Bandyopadhyay, J., Lee, J., Lee, J.I., Yu, J.R., Jee, C., Cho, J.H., Jung, S., Lee, M.H., Zannoni, S., Singson, A., Kim do, H., Koo, H.S., and Ahnn, J. (2002). Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is involved in movement, fertility, egg laying, and growth in Caenorhabditis elegans. Mol Biol Cell 13(9):3281-3293.

9. Lee, M.H., Ahn B., Choi I.S., and Koo H.S. (2002) The gene expression and deficiency phenotypes of Cockayne syndrome B protein in Caenorhabditis elegans. FEBS Lett. 522:47-51.

10. Lee J., Jee C., Lee J.I., Lee, M.H., Lee M.H., Koo H.S., Chung C.H., and Ahnn J. (2001) A deubiquitinating enzyme, UCH/CeUBP130, has an essential role in the formation of a functional microtubule-organizing centre (MTOC) during early cleavage in C. elegans. Genes Cells. 6(10):899-911.

11. Lee, M.H., Park H., Shim G., Lee J., and Koo H.S. (2000) Regulation of gene expression, cellular localization, and in vivo function of Caenorhabditis elegans DNA topoisomerase I. Genes Cells. 6(4):303-12.

12. Lee, M.H., Jang Y.J., and Koo H.S. (1998) Alternative splicing in the Caenorhabditis elegans DNA topoisomerase I gene. Biochim Biophys Acta. 1396(2):207-14.

Invited Seminars

RIKEN-CDB, Kobe, Japan (2009)

Platform presentation: C. elegans; a simple approach to understand stem cell.

Brody school of Medicine, East Carolina University, NC, USA (2008)

Platform presentation: C. elegans; a simple approach to understand stem cell.

University of Dundee, UK (2008)

Video presentation: Controls of Germline Stem Cells by Notch and MAPK signaling pathways.

University of Ulm, Ulm, Germany (2008)

Platform presentation: Molecular control of C. elegans germline stem cells: Notch signaling and an RNA/MAPK regulatory network.

EMBL, Heidelberg, Germany (2007)

Platform presentation: Germ cell fate specification and its regulation in C. elegans germ line.

UW-Madison, WI, USA: Campus Stem Cell meeting (2007)

Platform presentation: PUF proteins control MAP kinase expression in C. elegans and human embryonic stem cells.

Annual meeting of Korean Society for Biochemistry, Daejon, Korea (2002).

Platform presentation: C. elegans Dna2 is required for DNA replication and repair.

Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Symposium, Beijing, China (2000). Platform presentation: Expressional regulation and in vivo function of C. elegans DNA topoisomerase I.