• 제목/요약/키워드: Personalized medicine

검색결과 263건 처리시간 0.021초

The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNA-Induced Silencing of NF-κB-Inducing Kinase

  • Jang, Hanbit;Park, Seulki;Kim, Jaehoon;Kim, Jong Hwan;Kim, Seon-Young;Cho, Sayeon;Park, Sung Goo;Park, Byoung Chul;Kim, Sunhong;Kim, Jeong-Hoon
    • Molecules and Cells
    • /
    • 제43권1호
    • /
    • pp.23-33
    • /
    • 2020
  • NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB-inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the TP53 gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.

"아시아인 건강을 위한 한국인 게놈" : 한국인 유전체 프로젝트의 상업화 전략 ("The Korean Genome for Asian Health": A Commercialization Strategy of the Korean Genome Projects)

  • 현재환
    • 과학기술학연구
    • /
    • 제19권2호
    • /
    • pp.117-167
    • /
    • 2019
  • 인간 유전체 프로젝트의 초안 발표 이후 여러 한국인 유전체 프로젝트들이 추진되었다. 그 결과 등장한 한국인 유전체를 둘러싼 흥미로운 담론 중 하나는 "한국인 유전체" 서열 분석을 통해 "아시아인 맞춤의학"을 구현할 수 있다는 주장이다. 본 논문은 이를 한국 유전체 학자들이 자국민에 대한 유전체 자료를 상업화하려는 노력 가운데 발전시킨 전략으로 인지하고, 이 "아시아인 건강을 위한 한국인 게놈" 전략이 출현하게 된 배경을 역사적으로 검토한다. 이 글은 한국 유전체 프로젝트들의 전략이 탈식민 국가들에서 빈번하게 발견되는 "유전체 주권"(genome sovereignty) 정책이 2000년대 초반 이후 한국에서 주요 정책 의제로 부상한 아시아 지역주의와 결합하여 등장한 산물이라고 주장한다. 이를 통해 이 연구는 그간 범아시아 SNP 컨소시엄(Pan-Asian Single Nucleotide Polymorphism Consortium)을 중심으로 논의된 유전체학과 아시아인의 구성에 관한 과학기술학 연구가 국소적인 아시아인 관념과 아시아 지역주의를 가진 싱가포르의 경험을 지나치게 일반화해왔음을 지적한다. 이와 함께 한국 유전체학 거버넌스에서 과학기술학자들이 맡을 수 있는 역할에 대해서도 고민해 볼 기회를 제공할 것이다.

The Short-Chain Fatty Acid Receptor GPR43 Modulates YAP/TAZ via RhoA

  • Park, Bi-Oh;Kim, Seong Heon;Kim, Jong Hwan;Kim, Seon-Young;Park, Byoung Chul;Han, Sang-Bae;Park, Sung Goo;Kim, Jeong-Hoon;Kim, Sunhong
    • Molecules and Cells
    • /
    • 제44권7호
    • /
    • pp.458-467
    • /
    • 2021
  • GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca2+ flux via coupling to Gαi and Gαq families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gαq/11 and Gα12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

사상체질에 따른 생활습관이 대사증후군 및 위험군에 미치는 영향 (Effects of Life Style on Metabolic Syndrome Stage according to the Sasang Constitution)

  • 김지영;이시우;백영화
    • 사상체질의학회지
    • /
    • 제29권3호
    • /
    • pp.232-241
    • /
    • 2017
  • Objectives This study was to identify the lifestyle associated with metabolic syndrome and to suggest a personalized health management according to the constitution to prevent disease by metabolic syndrome stage. Methods This study used the data of Korean medicine Data Center (KDC). A total of 8,985 data were searched for subjects who participated in Anseong and Ansan cohorts study from 2009 to 2012. We analyzed 2,602 participants that diagnosed with metabolic syndrome among the ages of 30 to 55. We divided into three groups, none, pre-metabolic syndrome (Pre-MetS), and metabolic syndrome (MetS), according to number of metabolic syndrome elements. Results The prevalence of metabolic syndrome was highest in Taeumin (Pre-MetS: 48.2%, MetS: 41.2%). The risk factors for metabolic syndrome are dietary amount, speed of eating, and sleep quality in Taeumin, and dietary amount and sleep quality in Soyangin. Conclusions The life style affecting the metabolic syndrome were different according to the constitution. It is necessary to manage life style considering the Sasang constitution

문헌고찰을 통해 알아본 2020년 체질 의료 서비스 시장 규모 (The Predicted Scale of Sasang Constitutional Medical Service Market in 2020)

  • 장은수
    • 사상체질의학회지
    • /
    • 제29권1호
    • /
    • pp.14-20
    • /
    • 2017
  • Objectives Recently, the demand for complementary & alternative and personalized medical service has increased in the world. The purpose of this study was to predict the future market size of constitutional medical service in Korea through past surveyed studies Methods The portal sites of OASIS, NDSL, RISS, KISS, Koreamed, were used to select the researches related with constitutional medical service market. Total 1,477 papers were identified and 43 of them were fully reviewed. Finally, three of them picked up. Two specialists joined this review. Results and Conclusion The rate of constitutional medical service market among Korean medical service market was 23.2% in 2004 survey, 26.6% in 2007, and 23.5% in 2010. The number of Korean medical clinics and hospital was assumed 17,118 in 2020. The market size of Korean medicine was predicted 698,929 ten million won and among them, the scale of constitutional market size was 181,171 ten million won which meaned 25.9% proportion of Korean medical market size. Conclusion Constitutional medical market seems to be developed faster than Korean medical market in future.

Risk Assessment and Pharmacogenetics in Molecular and Genomic Epidemiology

  • Park, Sue-K.;Choi, Ji-Yeob
    • Journal of Preventive Medicine and Public Health
    • /
    • 제42권6호
    • /
    • pp.371-376
    • /
    • 2009
  • In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

공개용 리소스를 활용한 Haplotype 재조합 시스템 개발 (Development of Haplotype Reconstruction System Using Public Resources)

  • 김기봉
    • 한국산학기술학회논문지
    • /
    • 제11권2호
    • /
    • pp.720-726
    • /
    • 2010
  • Haplotype은 연관성을 띠면서 함께 유전하는 SNP (Single Nucleotide Polymorphism) 집단을 반영하고 있기 때문에 맞춤의학 분야에서 haplotype기반의 연구 중요성이 지속적으로 급증하고 있다. in silico 방법을 바탕으로 Haplotype 재조합을 위해 현재 가장 널리 사용되는 공개용 리소스 응용소프트웨어로는 PL-EM, Haplotyper, PHASE 및 HAP 등이 있다. PL-EM, Haplotyper 및 PHASE 등은 리눅스와 유닉스 시스템에서 구동되는 명령라인 응용 소프트웨어이고, HAP는 클라이언트-서버 환경에서 웹기반으로 구동되는 소프트웨어이다. 본 논문에서는 실험적으로 검증된 데이터들을 이용하여 공개용 리소스 소프트웨어들의 정확성을 검증하고, 그러한 검증결과를 토대로 선별된 Haplotyper와 PL-EM 등으로 개발한 통합 haplotye 재조합 시스템에 대해 소개하고자 한다. 개발된 통합 시스템은 사용자 친화적 웹 인터페이스를 갖는 클라이언트-서버 시스템으로 최종 사용자들에게 양질의 haplotype 분석 결과를 제공할 수 있다. Haplotyper의 경우 5명의 개체로부터 얻은 길이가 5인 SNP 유전자형 데이터를 가지고 결과를 분석하였고, PL-EM의 경우 15명의 개체로부터 얻은 길이가 13인 SNP 유전자형 데이터를 가지고 결과를 분석하였다. 그 결과 본 시스템은 두 부분으로 나누어 개개인의 haplotype 정보와 haplotype 집단 정보를 이해하기 쉽게 체계적으로 제공하는 것을 확인하였다. 이러한 측면에서 본 시스템은 haplotype 지도 작성을 통한 질병 유전자 발굴 및 맞춤의약 개발 연구에 매우 유용한 도구로 사용될 수 있으리라 여겨진다.

Finding Genetic Risk Factors of Gestational Diabetes

  • Kwak, Soo Heon;Jang, Hak C.;Park, Kyong Soo
    • Genomics & Informatics
    • /
    • 제10권4호
    • /
    • pp.239-243
    • /
    • 2012
  • Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy that is suspected to have a strong genetic predisposition. It is associated with poor perinatal outcome, and both GDM women and their offspring are at increased risk of future development of type 2 diabetes mellitus (T2DM). During the past several years, there has been progress in finding the genetic risk factors of GDM in relation to T2DM. Some of the genetic variants that were proven to be significantly associated with T2DM are also genetic risk factors of GDM. Recently, a genome-wide association study of GDM was performed and reported that genetic variants in CDKAL1 and MTNR1B were associated with GDM at a genome-wide significance level. Current investigations using next-generation sequencing will improve our insight into the pathophysiology of GDM. It would be important to know whether genetic information revealed from these studies could improve our prediction of GDM and the future development of T2DM. We hope further research on the genetics of GDM would ultimately lead us to personalized genomic medicine and improved patient care.

Generation of Whole-Genome Sequencing Data for Comparing Primary and Castration-Resistant Prostate Cancer

  • Park, Jong-Lyul;Kim, Seon-Kyu;Kim, Jeong-Hwan;Yun, Seok Joong;Kim, Wun-Jae;Kim, Won Tae;Jeong, Pildu;Kang, Ho Won;Kim, Seon-Young
    • Genomics & Informatics
    • /
    • 제16권3호
    • /
    • pp.71-74
    • /
    • 2018
  • Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.

Perspectives on Clinical Informatics: Integrating Large-Scale Clinical, Genomic, and Health Information for Clinical Care

  • Choi, In Young;Kim, Tae-Min;Kim, Myung Shin;Mun, Seong K.;Chung, Yeun-Jun
    • Genomics & Informatics
    • /
    • 제11권4호
    • /
    • pp.186-190
    • /
    • 2013
  • The advances in electronic medical records (EMRs) and bioinformatics (BI) represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO) aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.