Rong Liu, PhD

Research Interests

​Molecular Motor Proteins; Cytoskeleton; Sensory Function and Disease; Cargo Transport in Neurons

Usher Protein Dynamics in Hair Cell Function and Deafness

A major focus of our research is to unravel the mechanisms involved in the trafficking, assembly, and function of stereociliar proteins and to understand how these processes are affected in hearing loss.



Hair cell stereocilia are actin-rich membrane protrusions with the ability to convert sound-induced vibrations into electrical signals. At the heart of hair cell mechanotransduction is the tip link, a cadherin-based filament that connects the MET channel to the taller neighboring stereocilium. When the hair bundle deflects, the tip link conveys force to open the MET channel. Actin-based motor myosin-7a is localized at the upper end of the tip link and regulates the tip link's resting tension and hair cell mechanosensitivity.

Genetic defects of any of the five proteins: myosin-7a (USH1B), sans (USH1G), harmonin-b (USH1C) as well as the tip link proteins cadherin-23 (USH1D) and prtocadherin-15 (USH1F) are causative for Usher syndrome type 1, the most severe form deaf-blindness in humans. Patients with the Type 1 Usher syndrome display profound congenital hearing loss, vestibular dysfunction, and childhood-onset vision loss, underscoring the importance of Usher-1 proteins in the sensory processes. 



Our previous research has made major contribution to myosin-7a-based transport, where we detailed the molecular process by which myosin-7a undergoes cargo-dependent dimerization and form a processive transporter capable of moving for long range along actin. Our current research focuses on human myosin-7a holoenzyme and determine its roles in Usher protein trafficking and function during the hearing process.

Molecular Mechanism of Kinesin-2 in Photoreceptor Trafficking

Cilia are microtubule-based organelles that play crucial roles in the sensory systems including vision. In the neuroretina, the outer segment (OS) of photoreceptors are unique light-sensitive cilia that detect and transduce light into neurological signals. Genetic defects in cilia cause a group of inherited conditions, known as ciliopathies, with clinical manifestations often including retinal dystrophy and blindness.

The assembly and function of cilia requires intraflagellar transport (IFT), a bidirectional movement along cilia powers by motor-IFT complexes. Kinesin-2 motors drive the anterograde IFT and ciliogenesis. Its defects are associated with syndromic and non-syndromic retinal ciliopathies in human patients.

Our research seeks to understand the molecular mechanism by which kinesin-2 transport IFT train along ciliary axoneme, and to decipher how its mutations cause the molecular defects that lead to ciliopathies and retinitis pigmentosa. We address these questions using a combination of biochemical, structural, single-molecule, and modern microscopic approaches.

Link to the Lab Website

Grants and Research

NIH R01 Rong Liu (PI) 12/2024 – 11/2029

Significance of Usher Protein Dynamics in Hair Cell Function and Deafness                             $ 2,182,205

This project aims to unravel the mechanisms behind the trafficking and assembly of Usher-1 interactome. the key molecular complex involved in the mechanotransduction process of auditory hair cells. Results are expected to provide critical insights into pathophysiology of Usher protein-related hearing loss, with the aim of identifying novel therapies for patients with Usher syndrome and other non-syndromic deafness.

NIH P20 Rong Liu (PPL) 01/2023 – 12/2024

Mechanistic Analysis of Kinesin-2 Motility and Its Regulation for Ciliary Trafficking              $228,000

This project aims to investigate the mechanisms by which kinesin-2 powers the anterograde transport within the cilia and the pathophysiology of its mutations in human patients that lead to ciliopathies.

Publications

[2024]

• Wright M, Redford S, Vehar J, Courtney KC, Billington N & Liu R. MultiBac system-based purification and biophysical characterization of human myosin-7a. J Vis Exp. 2024 Aug 23: (210). PMID: 39248532

[2023]

• Holló A, Billington N, Takagi Y, Kengyel AM, Sellers JR & Liu R. Molecular regulatory mechanisms of human myosin-7a. J Biol Chem. 2023 Sep 8; 105243 PMID: 37690683

[2022]

• Hannaford MR, Liu R, Billington N, Swider ZT, Galletta BJ, Fagerstrom CJ, Combs C, Sellers JR, Rusan NM. Pericentrin interacts with kinesin-1 to drive centriole motility. J Cell Biol. 2022 Sep 5;221(9):e202112097

[2021]

• Liu R, Billington N, Yang Y, Bond C, Hong A, Siththanandan V, Takagi Y & Sellers JR. A binding protein regulates myosin-7a dimerization and actin bundle assembly. Nat Commun. Jan 25; 12(1): 563.
• Nishimura Y, Shi S, Zhang F, Liu R, Takagi Y, Bershadsky AD, Viasnoff V & Sellers JR. The formin inhibitor, SMIFH2, inhibits members of the myosin superfamily. J Cell Sci. Feb 23: jcs.253708.

[2020]

• Lu W, Lakonishok M, Liu R, Billington N, Rich A, Glotzer M, Sellers JR & Gelfand VI. Competition between kinesin-1 and myosin-V defines Drosophila posterior determination. Elife Feb 14;9
• Pal K, Nowak R, Billington N, Liu R, Ghosh A, Sellers JR & Fowler VM. Megakaryocyte migration defects due to nonmuscle myosin IIA mutations underly thrombocytopenia in MYH9-related disease. Blood May 21;135

Complete List of Publications