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Kyu-ho Lee

Title
InstitutionMedical University of South Carolina
DepartmentPediatrics
AddressP.O. Box MSC 915
CR 615
173 Ashley Ave.
Phone843-792-0307
Fax843-792-0664
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    Collapse Biography 
    Collapse awards and honors
    2008Rubin Mitchell Award for Outstanding Young Investigator in Pediatric Research, Medical University of South Carolina
    2012 - currInvited Member, Scientific Advisory Board, Preeclampsia Registry and BioBank, Preeclampsia Foundation

    Collapse Overview 
    Collapse overview
    The Lee laboratory focus on early heart development, particularly as it pertains to mechanisms causing congenital heart disease in humans.

    We currently study the genetic pathways leading to and emanating from the early cardiac transcription factor, Nkx2-5, which has long been associated with congenital anomalies. Alteration of Nkx2-5 expression levels has a profound effect on development of the Second Heart Field (SHF), a distinct set of heart precursors which gives rise to both outflow tract (OFT) and right ventricle at the aortic pole of the embryonic heart. Disruption of Nkx2-5 expression in mouse models results in a spectrum of defects from severe hypoplasia of OFT and right ventricle to milder OFT rotation or alignment defects such as double outlet right ventricle (DORV). Missense mutations of Nkx2-5 in human kindreds are similarly associated with OFT defects like DORV and Tetralogy of Fallot. This represents a significant clinical association: of the congenital heart anomalies that occur in nearly one percent of all human live births, nearly one-third involve the OFT and associated aorta and pulmonary artery.

    Our efforts are directed towards two main pathways to discovery:

    Identification of the direct downstream gene targets of the Nkx2-5 transcription factor in cells of the second heart field.
    Delineation of the transcriptional regulation of Nkx2-5 in second heart field.
    The Lee laboratory has also begun a pilot effort to understand the linkage between ectopic expression of Nkx2-5 in human placenta, and pre-eclampsia, or hypertension and proteinuria in pregnancy. Pre-eclampsia (PE) occurs in 2-7% of all pregnancies, and is a leading cause of maternal morbidity and premature birth. We have recently found unusually high levels of Nkx2.5 expression in placental trophoblast cells in a subset of women with early onset and severe pre-eclampsis (EOSPE) associated with high levels of an emerging marker of pre-eclampsia, the anti-angiogenic factor sFlt-1. We hypothesize that this linkage is due to the activation of expression of an Nkx2-5 target gene, khdrbs1/Sam68, which may influence production of sFlt-1 transcripts through regulation of alternative mRNA splicing of the parent VEGFR1 RNA.

    Interestingly, the statistical linkage between Nkx2-5 and sFlt-1 levels show racial differences, which may lead to novel insights into both distinct causes of PE between individuals, and the factors related to differential disease incidence and severity between racial groups.

    Lee lab PE research efforts are directed toward human and animal model efforts:

    Expanded human tissue expression profiling to further explore racial and etiologic associations between elevated Nkx2-5 and target gene expression and disease.
    Use of mouse models testing the effect of abnormal Nkx2-5 expression in the placenta on development and maternal morbidity during pregnancy.

    Collapse keywords
    Pediatric Cardiology, Cardiac Development: Genetics and Transcriptional Control, Molecular Mechanisms of Pre-eclampsia

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    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Lauriol J, Cabrera JR, Roy A, Keith K, Hough SM, Damilano F, Wang B, Segarra GC, Flessa ME, Miller LE, Das S, Bronson R, Lee KH, Kontaridis MI. Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. J Clin Invest. 2016 08 01; 126(8):2989-3005. PMID: 27348588.
      View in: PubMed
    2. Rivers ER, Horton AJ, Hawk AF, Favre EG, Senf KM, Nietert PJ, Chang EY, Foley AC, Robinson CJ, Lee KH. Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia. Hypertens Pregnancy. 2014 Nov; 33(4):412-26. PMID: 24987805.
      View in: PubMed
    3. Clark CD, Zhang B, Lee B, Evans SI, Lassar AB, Lee KH. Evolutionary conservation of Nkx2.5 autoregulation in the second heart field. Dev Biol. 2013 Feb 01; 374(1):198-209. PMID: 23165293.
      View in: PubMed
    4. Barth JL, Clark CD, Fresco VM, Knoll EP, Lee B, Argraves WS, Lee KH. Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis. Dev Dyn. 2010 Jul; 239(7):2024-33. PMID: 20549724.
      View in: PubMed
    5. Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR, Pu WT. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol. 2009 Apr; 29(8):2193-204. PMID: 19188439.
      View in: PubMed
    6. Rivera-Feliciano J, Lee KH, Kong SW, Rajagopal S, Ma Q, Springer Z, Izumo S, Tabin CJ, Pu WT. Development of heart valves requires Gata4 expression in endothelial-derived cells. Development. 2006 Sep; 133(18):3607-18. PMID: 16914500.
      View in: PubMed
    7. Lee KH, Evans S, Ruan TY, Lassar AB. SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer. Development. 2004 Oct; 131(19):4709-23. PMID: 15329343.
      View in: PubMed
    8. Miller CT, Schilling TF, Lee K, Parker J, Kimmel CB. sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development. Development. 2000 Sep; 127(17):3815-28. PMID: 10934026.
      View in: PubMed
    9. Angelo S, Lohr J, Lee KH, Ticho BS, Breitbart RE, Hill S, Yost HJ, Srivastava D. Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac, branchial arch and lateral mesoderm development. Mech Dev. 2000 Jul; 95(1-2):231-7. PMID: 10906469.
      View in: PubMed
    10. Lee KH, Marden JJ, Thompson MS, MacLennan H, Kishimoto Y, Pratt SJ, Schulte-Merker S, Hammerschmidt M, Johnson SL, Postlethwaite JH, Beier DC, Zon LI. Cloning and genetic mapping of zebrafish BMP-2. Dev Genet. 1998; 23(2):97-103. PMID: 9770266.
      View in: PubMed
    11. Kishimoto Y, Lee KH, Zon L, Hammerschmidt M, Schulte-Merker S. The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development. 1997 Nov; 124(22):4457-66. PMID: 9409664.
      View in: PubMed
    12. Lee KH, Xu Q, Breitbart RE. A new tinman-related gene, nkx2.7, anticipates the expression of nkx2.5 and nkx2.3 in zebrafish heart and pharyngeal endoderm. Dev Biol. 1996 Dec 15; 180(2):722-31. PMID: 8954740.
      View in: PubMed
    13. Lee KH, Bowen-Pope DF, Reed RR. Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium. Mol Cell Biol. 1990 May; 10(5):2237-46. PMID: 2157969.
      View in: PubMed
    14. Lee KH, Wells RG, Reed RR. Isolation of an olfactory cDNA: similarity to retinol-binding protein suggests a role in olfaction. Science. 1987 Feb 27; 235(4792):1053-6. PMID: 3493528.
      View in: PubMed
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