Eun D. Lee, Ph.D.
Department of Obstetrics and Gynecology
Sanger Hall, Room 11-028B
1101 East Marshall Street
Richmond, VA 23298-0034
Preeclampsia (PreE) is a leading cause of maternal and fetal morbidity and mortality. Unfortunately, African American women are three times more likely to face death from PreE although the causative factors remain unknown. Our group has shown that variation in the fetal endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is associated with PreE in African Americans. However, the exact molecular mechanisms by which PreE is caused or why African-American women have a significantly greater risk is yet to be determined. ERAP2 is a good candidate to further explore its contribution to PreE because it is expressed on placenta, participates in immune response, inflammation, and blood pressure regulation. Dr. Lee’s research will expand our existing knowledge of ERAP2 and clarify specifically how immunological response to ERAP2 variable proteins plays a critical role in PreE. The discovery of genetic determinants and understanding pathophysiology of PreE will contribute significantly to devising preventative treatment, maintaining healthy pregnancy, and preventing premature birth. Her research focuses on 1) single nucleotide polymorphisms (SNPs) in ERAP2; 2) the maternal killer immunoglobulin-like receptors (KIRs) on decidual Natural Killer (dNK) cells; and 3) the Human Leukocyte Antigen (HLA) genetic variation on trophoblasts cells.
1. Defining the role of ERAP2 and its isoforms in modulation of immune cell activation, killing ability and cytokine profiles.
2. Determining the immune evasion mechanism in pregnancy and cancer via ERAP2 and its isoforms.
3. Characterizing cytotoxic and allogeneic immune cells in cord blood, maternal peripheral blood, and decidual tissue of normal and PreE subjects.
Molecular biology (PCR, allelic discrimination, gel electrophoresis, sequencing, Western blot analysis, and vector/plasmid design), cellular model (transfection, transformation, cell killing assays and lymphocyte activation assays), flow cytometry, microscopy, knock-in animal models, xenograft animal models, 3-D imagining, and IHC.
Department of Obstetrics and Gynecology.
NIH-NICHD R01 HD073555-S1
- Lee ED, Franzese S, Hilliard D, Teves M, Ramus, R, Strauss, J. Comparative Expression Profiling of Endoplasmic Reticulum Aminopeptidase 2 and Human Leukocyte Antigen-C Expression in Choriocarcinoma Cell Lines. Placenta, 2014; 35: 9, 665-790.
- Warthan MD, Washington SL, Franzese SE, Costin BN, Ramus RM, Kim KR, Stratikos E, Strauss JF, Lee ED. The Role of ERAP2 in Modulating Immune Recognition of Choriocarcinoma. 2017 (Biology of Reproduction; pending)
- Lee ED. Endoplasmic Reticulum Aminopeptidase 2, a common link to adverse pregnancy outcomes and cancer? Placenta, 2017; Vol. 56:p. 40-43.
- Gorse, K, Lantzy MK, Lee ED and Lafrenaye A. Trpm4 induces astrocyte swelling but not death after diffuse traumatic brain injury: 2017 (Journal of Neurotrauma; pending).
Vanhille, D.L., Hill, L.D., Hilliard, D.D., Lee, E.D., Teves, M.E., Srinivas, S., Kusanovic, J.P., Gomez, R., Stratikos, E., Elovitz, M.A., Romero, R., Strauss III, J.F. (2013) A Novel ERAP2 Haplotype Structure in a Chilean Population: Implication for ERAP2 Protein Expression and Preeclampsia Risk. Molecular Genetics and Genomic Medicine, vol. 1, issue 2: 98-107, 2013.
- Dale Stapler,* Eun D. Lee,* Saranya A. Selvaraj,* Andrew G. Evans,† Leslie S. Kean,* Samuel H. Speck,† Christian P. Larsen,* and Shivaprakash Gangappa2* Expansion of Effector Memory TCR Vβ4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance1. The Journal of Immunology, 180: 3190 –3200, 2008.
- Han Lee, E.D., Kemball, C.C., Wang, J., Dong, Y., Stapler, Jr., D.C., Hamby, K., Newell, K.A., Pearson, T.C., Lukacher, A.E., and Larsen, C.P. A mouse model for polyomavirus-associated nephropathy of kidney transplants. American Journal of Transplantation, 6: 913-922, 2006. (See related commentary.)
- Sonya Washington (Research Coordinator)