Ph.D., University of Texas Southwestern Medical Center at Dallas
Postdoctoral Fellow, Genentech, Inc.
This laboratory is interested in understanding the basic and translational biology of two cell-surface protein families. The first receptor protein family is composed of single transmembrane receptors containing the guanylyl cyclase (GC) domain that produces cyclic guanosine 3』,5』-monophosphate (cGMP) as the intracellular second messenger. Our research mainly focuses on two recently discovered members, mouse GC-G and fruit fly BdmGC-1. The second protein family composed of three independent genes, named SCUBE1 to 3, was identified by this group through genomic mining. These genes encode ~1,000 amino acid polypeptides share a conserved protein domain structure of at least five recognizable motifs: an NH2-terminal signal peptide sequence, 9 tandem repeats of epidermal growth factor (EGF)-like modules, a large N-glycosylated spacer region followed by three repeated stretches of 6-cysteine residues with unique and regular spacing, and one CUB domain at the COOH-terminus. A combination of the molecular, biochemical, genetically-altered mouse methodologies has been using to unravel the physiological and pathological functions of these novel cell-surface proteins. Our results demonstrate their basic functions and translational implications in developmental processes and numerous human diseases such as acute renal failure, acute ischemic / thrombotic diseases, and breast cancer progression.
本研究室目前的研究主題在於探討兩種新的細胞表面蛋白家族之生物功能及其臨床應用。第一類是鳥甘酸環化酶受體 (guanylyl cyclase receptor) 蛋白家族,此蛋白群為單一穿膜 (single transmembrane) 之受體,具鳥甘酸環化酶活性,以產生cyclic GMP為二級訊息分子,來調控生理反應。我們研究以最新之家族成員GC-G為主。第二類是由本實驗室以基因體方法發現之三個嶄新基因所組成的家族,具有細胞表面表達之特性,且帶有多重的類上皮細胞生長因子區域 (epithelial growth factor-like domain) 和一個CUB (complement protein C1r/C1s, Uegf, and Bmp1) 區域,分別命名為SCUBE1 to 3。我們已利用分子、生物化學研究方法、小鼠基因轉殖及基因剔除之技術來探討這些細胞表面蛋白之病理及生理功能。最近研究發現這些蛋白可能參與多種疾病 (如:急性腎衰竭、急性冠狀動脈性及急性缺氧性心臟病、乳癌) 之發生且具臨床應用之價值。