Transition Program in Clinical Research

目前正在积极招募和研究先天性糖基化障碍（CDGs）和其他单基因综合征患者，并伴有与结缔组织异常相关的严重过敏性疾病。为了实现这些目标，在实验室中开发了许多临床检测方法：以凝集素为基础的流式细胞术用于表征n-聚糖异常；ddPCR检测已经发展到执行胰蛋白酶基因分型和测定异构体特异性基因表达。利用分子遗传技术，我们继续表征我们在离散免疫途径和糖基化过程中发现的缺陷。为此，我们采用了许多技术，包括细胞转染和小分子、sirna、shrna和抗体的途径抑制。当我们描述改变的糖基化在过敏性疾病和反应中的作用时，我们寻求设计方法来操纵这些途径来限制或改变疾病的发病机制。

Patients with Congenital Disorders of Glycosylation (CDGs) and other monogenic syndromes presenting with severe allergic disease in association with connective tissue abnormalities are actively being recruited and studied. A number of clinical assays have been developed in the laboratory in order to accomplish these goals: lectin-based flow cytometry is employed to characterize N-glycan abnormalities; ddPCR assays have been developed to perform tryptase genotyping and assay isoform-specific gene expression. Using molecular genetic techniques, we continue to characterize defects we have identified in discrete immune pathways and in glycosylation processes. To do so, we employ a number of techniques including cellular transfection and pathway inhibition with small molecules, siRNAs, shRNAs, and antibodies. As we characterize the role that altered glycosylation plays in allergic diseases and reactions, we seek to devise ways to manipulate these pathways to limit or alter disease pathogenesis.