조산아에서 출생 직후 혈청 E-selectin 농도 및 기관흡인액 중성구 수와 신생아 만성폐질환 발병과의 연관성

학위논문(석사)--서울대학교 대학원 :의학과 소아과학전공,2000.Maste

사람의 위암에서 종양 침윤 면역 세포가 환자의 예후에 미치는 영향

Thesis(doctors) --서울대학교 대학원 :의학과(병리학전공),2008. 8.Docto

LS 전선의 IB Deal 가능성 연구

Thesis(master`s)--서울대학교 경영전문대학원 :경영학과 Global MBA전공,2007.8Maste

Molecular network analysis of postnatal FMCD pathologic model

Focal Malformations of Cortical Development (FMCDs) lead to critical postnatal pathologies including drug-resistant pediatric epilepsy. However, although developmental pathologies are well-known, the mechanisms associated with more severe postnatal symptoms of FMCD should be studied further for efficient treatment. Thus, we applied transcription profiling to investigate the molecular networks associated with postnatal pathologies of FMCD. We produced pluripotent stem cell (hiPSC)-derived neural cells (NC) with AKT3 p.E17K, a FMCD-causing genetic mutation, and performed RNA-seq using this cell line. From the sequencing data, we formed the molecular networks of differentially expressed genes (DEGs) by protein-protein interaction. Then we found 1) extracellular matrix (ECM)-associated network and 2) synaptic function-associated network. Interestingly, DEGs from ECM network were highly overlapped with the results of the developmental study, but DEGs from synaptic function network were not. This result suggests that there are stage-specific etiologies, and the synaptic function network might be associated with postnatal pathologies. We will identify the effects of postnatal stage-specific networks to various FMCD pathologies. Then we aim to find possible treatment for specific clinical symptoms. To figure out the results in vivo postnatal model, we also plan to perform transposon system-mediated in utero electroporation in developing cortex. The discovery of postnatal stage-specific mechanisms will provide new therapeutic strategies of FMCD as well as provide key insights to understand the neurodevelopmental disease.1

In vitro and in vivo optimization of Destabilizing Domain in neuron for modeling brain disease

The destabilizing domain (DD) from Escherichia coli dihydrofolate reductase (ecDHFR) is a relatively small protein (158 a.a), which can conditionally control the abundance of a protein of interests (POIs) by a molecular chaperone, trimethoprim (TMP). The DD, allowed an ideal approach for reversibly and repeatedly regulating protein stability, has been used successfully to control the protein level and potentially activity. Therefore, we aim to test the usability of the DD for selectively regulating protein stability in neurons in vivo and in vitro. First, we utilized the PiggyBac (PB) transposon system for moderate and permanent expressions of candidate genes by genome integration. Using in utero electroporation (IUE), we introduced DD-YFP to developing ventricle at embryonic day 15.5 followed by TMP administration at postnatal day 14. Strong YFP fluorescence was detected 6hr after the administration of TMP whereas minimal or no YFP fluorescence was detected in untreated group suggesting effective stabilization of DD-YFP by TMP and minimal leakage in the absence of TMP. Currently, we are generating stable human embryonic stem cell (hESC) lines expressing DD-tagged GFP followed by neuronal differentiation to validate the TMP-induced stabilization of GFP in vitro. Altogether, our study will reveal the usability of the DD for selectively regulating protein stability in neurons in vivo and in vitro.1

Pathogenic Mechanism of Epilepsy in Sebaceous Nevus Syndrome by Dysregulation of RAS/MAPK Pathway

RAS/MAPK pathway involves not only biological processes such as differentiation, proliferation, and migration but also many diseases such as cancer. RASopathies, which are a group of developmental disorders caused by mutation of the RAS/MAPK pathway component, suggest the crucial role of this pathway in normal development. Sebaceous nevus syndrome (SNS), one of the RASopathies, is caused by somatic gain-of-function mutation of HRAS or KRAS. The symptoms of SNS include central-nervous system-related defects such as cerebral defects, intellectual disability, and epilepsy. To examine the pathogenesis of neurological symptoms in SNS, we generated the disease mouse model by overexpression of KRAS p.G12V in developing cortex using in utero electroporation. This model successfully recapitulated histological manifestations observed in the patient, such as heterotopic neurons, gliosis, and hypomyelination. It also showed abnormal neuronal differentiation and migration and neuronal dysmorphogenesis. To investigate neuronal excitability at a cellular level, we analyzed electrophysiological properties using patch-clamp. Both neurons with and without KRAS p.G12V overexpression showed hyperexcitability. Interneurons also showed abnormal action potential properties. To elucidate the molecular mechanism underlying observed pathological phenotypes in SNS, we generated drug-inducible KRAS pathogenic mutation expressing human NPC line using destabilization domain. In this cell line, several pathological phenotypes were rescued by ceasing the expression of the pathogenic mutation at the neuron stage. Stage-specific modulation of the KRAS variant will allow us to characterize molecular and cellular phenotypes that can be reversed. Taken together, these results indicate how KRAS p.G12V interrupts normal brain development and leads to neuropathology including epilepsy in SNS and suggest the possibility of relieving neurological symptoms in SNS patients by recently developed KRAS inhibitors.2

Adenoma of the Nipple

Adenoma of the nipple (AN) is an uncommon benign tumor of the breast. This tumor usually arises from the lactiferous ducts of the nipple. The common clinical findings are unilateral serosanguinous discharge with crust and a palpable nodule in the nipple. The symptoms and signs of AN are similar to those of Paget`s disease and this confusion sometimes leads to unnecessary mastectomy. Thus performing careful clinical and histological examinations along with radiologic investigations are very important for the proper management of AN. This tumor is usually treated by total excision of the nipple. We report here on two cases of AN in two women who presented with red swelling, serosanguinous discharge and erosion of the nipple. We successfully managed them with partial excision or total excision along with reconstruction. Although AN is a relatively rare disease, Surgeons Should keep the diagnosis in mind for the proper management of this disease. (J Korean Surg Soc 2009;77:134-137)Lee HJ, 2002, J AM ACAD DERMATOL, V47, P578, DOI 10.1067/mjd.2002.122752Friedman EP, 1997, CLIN RADIOL, V52, P854MONTEMARANO AD, 1995, J AM ACAD DERMATOL, V33, P871BROWNSTEIN MH, 1985, J AM ACAD DERMATOL, V12, P707PERZIN KH, 1972, CANCER, V29, P996SHAPIRO L, 1965, AM J CLIN PATHOL, V44, P155TAYLOR HB, 1965, CANCER, V18, P995HANDLEY RS, 1962, BRIT J CANCER, V16, P187LEGAL Y, 1959, ANN ANAT PATHOL, V4, P292JONES DB, 1955, CANCER, V8, P315