Institute of Biological Chemistry, Academia Sinica

Research

Molecular Mechanism of Protein Transport

My research focuses on how intracellular protein transport is tightly regulated. Coat proteins, which initiate intracellular transport by coupling their roles in the vesicle formation and cargo sorting, are the best described to control the vesicular transport through their abilities to deform the membrane and directly bind to the cargo. ARF6 (ADP-Ribosylation Factor 6) is a small GTPase functioning in the regulation of endocytic recycling. Previously, I already defined the cargo adaptors, ACAP1 and AKT, both required for the endocytic recycling. ACAP1 (ARFGAP with Coil-coil, Ankyrin repeat and PH domain 1) is a GAP (GTPase-Activating Protein) for ARF6 to promote GTP hydrolysis of ARF6 and therefore to release ARF6 from the membrane. AKT is a serine/threonine kinase involving in many cellular processes, such as cell growth and migration. Although ACAP1 and AKT work together to regulate endocytic recycling, however, the upstream signaling that facilitates ACAP1 and AKT for the function of endocytic recycling remains unclear. In addition, how ACAP1 and AKT cooperate each other to form the complex for cargo sorting still needs to be resolved. These functional studies on the coat protein complexes will shed molecular insights into key physiologic and pathologic events, such as cell growth and migration.

Degrees and Positions Held

• 2008-2013   Ph.D., Institute of Molecular Medicine, National Taiwan University

• 2020-present   Joint Appointment Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2020-present   Assistant Professor, Institute of Biochemical Sciences, National Taiwan University
• 2019-2020   Visiting Specialist, Institute of Molecular Medicine, National Taiwan University
• 2015-2019   Postdoctoral Research Fellow, Harvard Medical School and Brigham & Women’s Hospital
• 2013-2015   Postdoctoral Research Fellow, Institute of Molecular Medicine, National Taiwan University

Selected Publications

The protein kinase Akt acts as a coat adaptor in endocytic recycling.  
Hsu JW*, Bai M*, Li K, Yang JS, Chu N, Cole PA, Eck MJ, Li J, Hsu VW (* equal contribution)  
Nat Cell Biol. (2020)

ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis.  
Yang JS, Hsu JW, Park SY, Lee SY, Li J, Bai M, Alves C, Tseng W, Michelet X, Ho IC, Hsu VW  
Nat Commun. (2019)

GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis.  
Yang JS, Hsu JW, Park SY, Li J, Oldham WM, Beznoussenko GV, Mironov AA, Loscalzo J, Hsu VW  
Nature (2018)

Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p.  
Hsu JW*, Tang PH*, Wang IH*, Liu CL, Chen WH, Tsai PC, Chen KY, Chen KJ, Yu CJ, Lee FJ (* equal contribution)  
Proc Natl Acad Sci U S A. (2016)

Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain.  
Hsu JW, Chen KJ, Lee FJ  
Nat Commun. (2015)

Publication List