Dr. Shen, Chen-Yang 沈志陽 博士
Ph.D. Univ. of North Carolina at Chapel Hill
Technological advances have provided opportunities that allow genetic variants in the whole genome to be analyzed in association studies, thus giving unique opportunity for identifying moderate risk alleles without prior knowledge of etiology. This genome-wide association studies (GWAS) have been successful in identifying the genetic component of predisposition to many human complex diseases. By applying novel and precise analytical methods, current research focuses on exploring the biological mechanisms underlying susceptibility loci known as causal variants. In three of our recent studies, based on the data of GWASs, we have demonstrated the molecular basis of important causal variants associated with breast cancer progression and hyperlipidemia with an emphasis on using post-GWAS analysis and experiments to gain insight into etiology. A series of experimental approaches, including the use of bioinformatic databases (such as eQTL and ENCODE), cell-based analyses and CRISPR/Cas9 genome-editing system, were used and identified specific transcription factors, which were able to discriminately bind to the specific alleles of these genetic variants. These studies demonstrate how post-GWAS studies can be conducted to generate useful information of translation relevance.
Our lab is also interested in breast cancer stem cell. We have identified specific marker, which is a long-non-coding RNA, that can be specifically identified estrogen-receptor-positive breast cancer stem cell. In addition, we have highlighted a microRNA-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.
Finally, we have introduced new approaches to explore possible contribution of histone overexpression, histone modification and DNA repair affecting breast cancer progression.
研究的長足進步提供現代生物醫學研究者獨特的機會分析整個基因體中的遺傳變異對複雜疾病發生進展與治療的影響. 更重要的是這種研究策略並不需要研究者對於疾病有任何預先的假設。這種全基因體相關研究(Genome-wide association study, GWAS)已成功發現許多複雜疾病易感性的遺傳因子, 並通過應用新穎的分析方法，當前的研究重點是探討因果變異的易感性便意味點的生物學機制。在我們研究室最近的三項研究中，我們依據此一策略找到了與乳癌進展和高脂血症相關的重要因果變異的分子機轉，這些研究的重點是使用 GWAS的結果,加以分析實驗來深入了解病因。我們使用一系列方法，包括使用生物資訊資料庫（如 eQTL 和 ENCODE）、細胞學分析和 CRISPR/Cas9 基因組編輯系統，我們的研究確定特定的轉錄因子能夠有區別地結合特定的遺傳變異點,進而影響下游基因的表現與疾病的生成。這些研究展現如何進行post-GWAS 研究來產生轉譯醫學的關鍵訊息。
我們實驗室也對乳癌幹細胞感到興趣。我們已經發現出特異性標記物(一種長鏈非編碼RNA)可以鑑定雌激素受體陽性乳癌幹細胞。此外，我們也找到了 microRNA主導的CXCR4/p-Akt 訊息抑制，從而影響了間質幹細胞的發生，這結果可以做為浸潤性乳腺癌治療的標靶。
最後，我們最近引入了新研究策略來探討組蛋白過表現、組蛋白修飾和 DNA 修復對乳腺癌進展的可能影響。
