Xiaowei Lu

Professor, Cell Biology

Primary Location

University of Virginia Health System, P.O. Box 800732,
Pinn Hall, Room 3025
Charlottesville, Virginia 22908

Primary Phone Number

434.982.6528

[email protected]

Website

https://lu-lab.vercel.app/

Bio & Overview

1. Wnt and PCP signaling in mechanosensory hair cell polarity. The actin-based hair bundle atop sensory hair cells is the mechanotransduction organelle essential for hearing and balance. A majority of sensorineural hearing loss (SNHL) disorders, including hereditary deafness, are caused by defects in the development or maintenance of the hair bundle. We investigate mechanisms underlying planar polarization of hair cells, which is crucial for the organization and orientation of the hair bundle. Our work in the last decade has provided fundamental new insights into a microtubule-based hair cell-intrinsic polarity machinery as well as intercellular Planar Cell Polarity (PCP) signaling for aligning hair cell orientation. Recently, we have uncovered a novel Wnt / heterotrimeric G protein / PI3K signaling pathway important for hair bundle morphogenesis This non-canonical Wnt signaling pathway coordinates cell-intrinsic and tissue-level PCP via multiple effectors, including PI3K, Rac1 and Gsk3b JCB 2020, Frontiers in Cell and Dev Biology, 2021). Current projects aim to elucidate the signal transduction machinery and downstream targets of the Wnt/G protein signaling pathway. 2. Innervation of auditory hair cells by spiral ganglion neurons. Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs), which are biopolar afferent neurons that transmit sound information received by hair cells to the central nervous system. During development, SGNs establish highly stereotyped connections with hair cell targets in the auditory sensory epithelium. Multiple type I SGNs innervate each inner hair cells to transmit sound signals, while type II SGNs innervate multiple outer hair cells to detect acoustic trauma. Recent findings suggest that PCP signaling is involved in the guidance of type II SGN peripheral projections. We are interested in identifying the axon guidance cues generated by the cochlear epithelium and how they are regulated by PCP signaling. Loss of functional connections between SGNs and HCs underlie hearing impairments caused by both genetic and environmental factors. Therefore, understanding the developmental programs that establish the highly stereotyped wiring patterns in the cochlea is crucial for circuit repair and regeneration following damage. 3. PCP signaling and biomechanical regulation of neural tube closure. We previously identified Ptk7, which encodes a receptor pseudokinase, as a key regulator of PCP and actomyosin contractility in multiple types of developing epithelia, such as the neural tube and the inner ear sensory epithelia. Ptk7 mutations have been identified in human patients with neural tube defects (NTD). However, how Ptk7 couples actomyosin contractility with the generation of planar polarity during neural tube morphogenesis is poorly understood. In collaboration with Dr. Ann Sutherland in the department, we leverage a CRISPR-generated Ptk7 allelic series carrying NTD patient variants and fluorescence imaging of cytoskeletal and Rho GTPase dynamics in intact live mouse embryos to understand biomechanical mechanisms crucial for neural tube morphogenesis.

Academic Information

Department: Cell Biology

Academic Title: Associate Professor

Primary Education

BS, Biochemistry, Peking University, 1991
PhD, Biology, Massachusetts Institute of Technology, 1998
Postdoc, Developmental Neurobiology, University of California, San Francisco & Stanford University, 2005

Other Appointments

Assistant Professor, Neuroscience
Assistant Professor, BMBG
Assistant Professor, MCDB

Other Affiliations

Member, Cancer Cell Signaling Program
MSTP
Associate Professor, BIMS

Research Interests

Wnt/PCP signaling in inner ear development Mouse models for human deafness Wnt/PCP signaling in neural tube closure

Research Disciplines

Biochemistry
Biology
Biophysics
Biotechnology
Cancer Biology
Cell and Developmental Biology
Development, Stem Cells & Regeneration
Experimental Pathology
Genetics
Infectious Diseases/Biodefense
Microbiology
Molecular Biology
Neuroscience
Structural Biology
Translational Science

Research Opportunities

Biochemistry
Cell Biology
Development, Stem Cells & Regeneration
Experimental Pathology
Neuroscience

PhD Programs

Cell Biology
Neuroscience

Selected Publications

2024

Xie N, Landin Malt A, Adylkhan A, Rodeman N, Moraes Borges R,. . . Lu X., (2024) Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 9. doi:10.1073/pnas.2405217121

2021

Landin Malt, A., Clancy, S., Hwang, D., Liu, A., Smith, C., Smith, M., . . . Lu, X. (2021). Non-Canonical Wnt Signaling Regulates Cochlear Outgrowth and Planar Cell Polarity via Gsk3β Inhibition. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9. doi:10.3389/fcell.2021.649830

2020

Malt, A. L., Hogan, A. K., Smith, C. D., Madani, M. S., & Lu, X. (2020). Wnts regulate planar cell polarity via heterotrimeric G protein and PI3K signaling. JOURNAL OF CELL BIOLOGY, 219(10). doi:10.1083/jcb.201912071

2019

Tarchini, B., & Lu, X. (2019). New insights into regulation and function of planar polarity in the inner ear. NEUROSCIENCE LETTERS, 709. doi:10.1016/j.neulet.2019.134373

Malt, A. L., Dailey, Z., Holbrook-Rasmussen, J., Zheng, Y., Hogan, A., Du, Q., & Lu, X. (2019). Par3 is essential for the establishment of planar cell polarity of inner ear hair cells. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(11), 4999-5008. doi:10.1073/pnas.1816333116

2017

Goodyear, R. J., Lu, X., Deans, M. R., & Richardson, G. P. (2017). A tectorin-based matrix and planar cell polarity genes are required for normal collagen-fibril orientation in the developing tectorial membrane. DEVELOPMENT, 144(21), 3978-3989. doi:10.1242/dev.151696

Lu, X., Guo, S., Cheng, Y., Kim, J. -H., Feng, Y., & Feng, Y. (2017). Stimulation of ovarian follicle growth after AMPK inhibition.. Reproduction (Cambridge, England), 153(5), 683-694. doi:10.1530/rep-16-0577

Feng, Y., Cui, P., Lu, X., Hsueh, B., Möller Billig, F., Zarnescu Yanez, L., . . . Hsueh, A. J. W. (2017). CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions.. Scientific reports, 7, 44810. doi:10.1038/srep44810

Feng, Y., Zhu, S., Antaris, A. L., Chen, H., Xiao, Y., Lu, X., . . . Hsueh, A. J. (2017). Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore.. Chemical science, 8(5), 3703-3711. doi:10.1039/c6sc04897h

2016

Xu, B., Washington, A. M., Domeniconi, R. F., Ferreira Souza, A. C., Lu, X., Sutherland, A., & Hinton, B. T. (2016). Protein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian duct. DEVELOPMENTAL BIOLOGY, 412(2), 219-233. doi:10.1016/j.ydbio.2016.02.029

2015

Lu, X., & Sipe, C. W. (2016). Developmental regulation of planar cell polarity and hair-bundle morphogenesis in auditory hair cells: lessons from human and mouse genetics. WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY, 5(1), 85-101. doi:10.1002/wdev.202

2014

Andreeva, A., Lee, J., Lohia, M., Wu, X., Macara, I. G., & Lu, X. (2014). PTK7-Src Signaling at Epithelial Cell Contacts Mediates Spatial Organization of Actomyosin and Planar Cell Polarity. DEVELOPMENTAL CELL, 29(1), 20-33. doi:10.1016/j.devcel.2014.02.008

Williams, M., Yen, W., Lu, X., & Sutherland, A. (2014). Distinct Apical and Basolateral Mechanisms Drive Planar Cell Polarity-Dependent Convergent Extension of the Mouse Neural Plate. DEVELOPMENTAL CELL, 29(1), 34-46. doi:10.1016/j.devcel.2014.02.007

2013

Sipe, C. W., Liu, L., Lee, J., Grimsley-Myers, C., & Lu, X. (2013). Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization. DEVELOPMENT, 140(8), 1785-1795. doi:10.1242/dev.089763

2012

Lee, J., Andreeva, A., Sipe, C. W., Liu, L., Cheng, A., & Lu, X. (2012). PTK7 Regulates Myosin II Activity to Orient Planar Polarity in the Mammalian Auditory Epithelium. CURRENT BIOLOGY, 22(11), 956-966. doi:10.1016/j.cub.2012.03.068

2011

Grimsley-Myers, C. M., Sipe, C. W., Wu, D. K., & Lu, X. (2012). Redundant functions of Rac GTPases in inner ear morphogenesis. DEVELOPMENTAL BIOLOGY, 362(2), 172-186. doi:10.1016/j.ydbio.2011.12.008

Sipe, C. W., & Lu, X. (2011). Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms. DEVELOPMENT, 138(16), 3441-3449. doi:10.1242/dev.065961

2010

Paudyal, A., Damrau, C., Patterson, V. L., Ermakov, A., Formstone, C., Lalanne, Z., . . . Murdoch, J. N. (2010). The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear. BMC DEVELOPMENTAL BIOLOGY, 10. doi:10.1186/1471-213X-10-87