IMM Research Seminar
Title：Signal Transduction Rewiring in Human Disease: a Systems Genetics Perspective
Speaker：Song Yi, Ph.D.
Department of Systems Biology,
The University of Texas MD Anderson Cancer Center, USA
Host：北京大学分子医学研究所 赵扬 (Tel. 6276-6138)
Cellular signal transduction in its core is a problem of molecular interactions. Proteins interact with other macromolecules in complex cellular networks to carry out biological function. How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. In this seminar, I discuss the current understanding of signaling transduction rewiring by genetic factors involved in a broad spectrum of human diseases. We functionally profile several thousand missense mutations using various interaction assays. While common variants from healthy individuals rarely affect signaling, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving most other interactions unperturbed. With transcription factors, many alleles that leave protein-protein interactions intact affect DNA binding. Different mutations in the same gene leading to different interaction profiles often result in distinct disease phenotypes. The integrative experimental and computational platform described here provides a practical approach to distinguishing the function of diverse candidate disease alleles emerging from genome sequencing projects. Our results also provide insights into reprograming signaling networks by external factors in the context of precision medicine.
Postdoc and graduate student positions available