Dr. Yuan Zhang

Regulation of α1-antitrypsin secretion

Background:

α1-antitrypsin (AAT) is a secreted glycoprotein with three N-linked glycans. After undergoing folding and quality control in the endoplasmic reticulum (ER), AAT molecules are moved to Golgi body. How AAT is transported from the ER to the Golgi is not well understood. In vitro studies identified LMAN1 as a potential cargo receptor for the ER-Golgi transport of AAT. LMAN1 is a mannose-binding lectin that forms a complex with MCFD2 and cycles between the ER and the cis-Golgi. We found that LMAN1 and MCFD2 deficiencies only lead to mild decrease of steady-state AAT levels in male mice. We hypothesize that alternative secretory pathways exist for AAT secretion. Our long-term interest is understanding how secretion of WT AAT and mutant AAT from AATD patients are regulated and developing new therapeutics to treat AATD.

AIM:

Aim 1. Elucidating the regulation of AAT secretion by LMAN1 and MCFD2.

Aim 2. Identifying novel genes encoding proteins controlling AAT secretion through a genome-wide CRISPR screen.

Curriculum vitae Dr. Yuan Zhang 

Dr. Yuan Zhang obtained her Ph.D degree in Microbiology from Wuhan University, China. Her Ph.D work focused on creating new or more effective genetically engineered vaccines against human viruses.

Since 2016 she has been working as a postdoctoral fellow in the Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, USA. The focus of her work is on understanding how secretion of glycoproteins such as AAT are regulated in health and diseases.