Zheng "John" Fu

Associate Professor, Pharmacology

Primary Location

1340 JPA, Pinn Hall 5217
PO Box 800735
Charlottesville, VA 22908-0708

Primary Phone Number

434.982.3204

Bio & Overview

My lab is interested in the molecular and cellular basis of human disease, with a focus on aberrant signal transduction of protein kinases in ciliopathies, a class of human diseases caused by genetic mutations affecting motile or non-motile (primary) cilia. Ciliopathies manifest developmental defects in nearly all human organ systems, including polycystic kidney disease, nephronophthisis, retinitis pigmentosa, the Bardet-Biedl syndrome, the Joubert syndrome, and the Meckel syndrome. A growing body of evidence has also linked cilia dysfunction to metabolic syndromes (e.g. obesity and diabetes), neurological disorders (e.g. epilepsy and Parkinson’s disease), and cancer (e.g. medulloblastoma). The primary cilium is a tiny microtubule-based apical membrane protrusion. It acts as an antenna for extracellular sensation and mediates intracellular signal transduction by compartmentalization of diverse signaling molecules including ion channels, receptors, enzymes, and second messengers. Our research seeks to define the molecular and biochemical basis for the control of primary cilia and cilia-dependent signaling as well as demonstrate the perturbations that result from human ciliopathy mutations. Currently we are focusing on the signaling mechanism and pathophysiologic functions of ciliogenesis associated kinase 1 (CILK1), formerly known as intestinal cell kinase (ICK), which has human variants associated with ciliopathies and epilepsy. Our lab uses knockout and knockin animal and cell models for both loss of function and gain-of-function approaches to advance our knowledge on fundamental mechanisms underlying cilia dysfunction in ciliopathies and epilepsy. Alterations of primary cilium and ciliary signaling events are implicated in cancer development. An emerging role for primary cilia in regulating cancer cell response to kinase inhibitors has provided a strong rationale for targeting ciliogenesis as a novel strategy to overcome drug resistance. In cancer cells, numerous oncogenic molecules, such as Smoothened, KRAS, EGFR, and PDGFR, are compartmentalized in the primary cilium. In the acquisition of drug resistance, cancer cells show increased cilia number/length and ciliary Hedgehog signaling. We are motivated by these premises to develop a novel pharmacological strategy to alter drug sensitivity of cancer cells by modulating their primary cilia and ciliary signaling.

Academic Information

Department: Pharmacology

Academic Title: Associate Professor

Primary Education

BS, Molecular Biology, NanKai University, Tianjin, P. R. China, 1994
PhD, Cell and Developmental Biology, University of Florida, Gainesville, FL, 1999

Other Appointments

Assistant Professor, Medicine
Assistant Professor, Biomedical Engineering
Assistant Professor, Gastroenterology
Postdoctoral Researcher, Pharmacology
Postdoctoral Researcher, Medicine- Gastroenterology and Hepatology
Assistant Professor, MOMD

Other Affiliations

Investigator, Cancer Center
Member, Cancer Cell Signaling Program
Faculty Fellow, Center for Global Health
Assistant Professor, BIMS

Research Interests

Molecular basis of ciliopathies; Signaling mechanisms of cilia-associated kinases

Research Disciplines

Biochemistry
Cancer Biology
Cell and Developmental Biology
Molecular Pharmacology

Research Opportunities

Biochemistry
Cancer Biology
Cell Biology

Selected Publications

2026

Fu, Z. (2026). Editorial: Signaling of Protein Kinases in Development and Disease. Biomedicines, 14(4), 788. https://doi.org/10.3390/biomedicines14040788

Fu, S. H., Park, C., Shah, N. A., Limerick, A., Powers, E. W., Mann, C. B., Hyun, E. M., Zhang, Y., Brautigan, D. L., Hao, S., Abounader, R., & Fu, Z.* (2026). Use of Small-Molecule Inhibitors of CILK1 and AURKA as Cilia-Promoting Drugs to Decelerate Medulloblastoma Cell Replication. Biomedicines, 14(2), 265. https://doi.org/10.3390/biomedicines14020265

2025

Carpenter, E.H., Chu, C., Limerick, A., Brautigan, D.L., Fu, Z.* (2025). Human disease variants of KATNIP fail to support CILK1 activation and control of primary cilia. JOURNAL OF CELL SCIENCE, 138(20):jcs264056. doi: 10.1242/jcs.264056.

2024

Limerick, A., McCabe, E.A., Turner J.S., Kuang, K.W., Gailey, C.D., Brautigan, D.L., Hao, Y., Chu, C., Fu, S.H., Ahmadi, S., Xu, W., Fu, Z.* (2024). An epilepsy-associate variant of CILK1 compromises KATNIP regulation and impairs primary cilia and Hedgehog signaling. CELLS, 13(15):1258. doi: 10.3390/cells13151258.

2023

Turner, J. S., Mccabe, E. A., Kuang, K. W., Gailey, C. D., Brautigan, D. L., Limerick, A., Wang, E.X., & Fu, Z.* (2023). The Scaffold Protein KATNIP Enhances CILK1 Control of Primary Cilia. MOLECULAR AND CELLULAR BIOLOGY, 43(9), 472-480. doi:10.1080/10985549.2023.2246870

2022

Wang, E. X., Turner, J. S., Brautigan, D. L., & Fu, Z.* (2022). Modulation of Primary Cilia by Alvocidib Inhibition of CILK1. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(15). doi:10.3390/ijms23158121

2021

Salvati, K. A., Mason, A. J., Gailey, C. D., Wang, E. J., Fu, Z.* & Beenhakker, M. P.* (2021). Mice Harboring a Non-Functional CILK1/ICK Allele Fail to Model the Epileptic Phenotype in Patients Carrying Variant CILK1/ICK. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(16). doi:10.3390/ijms22168875

Lai, D. -M., Bi, J. -J., Chen, Y. -H., Wu, Y. -D., Huang, Q. -W., Li, H. -J., Zhang, S., Fu, Z. & Tong, Y. -X. (2021). CCNI2 plays a promoting role in the progression of colorectal cancer. CANCER MEDICINE, 10(6), 1913-1924. doi:10.1002/cam4.3504

2020

Gailey, C. D., Wang, E. J., Jin, L., Ahmadi, S., Brautigan, D. L., Li, X., Xu, W., Scott, M. M., & Fu, Z.* (2021). PhosphositeT674Amutation in kinesin family member3Afails to reproduce tissue and ciliary defects characteristic ofCILK1loss of function. DEVELOPMENTAL DYNAMICS, 250(2), 263-273. doi:10.1002/dvdy.252

Wang, E. J., Gailey, C. D., Brautigan, D. L., & Fu, Z.* (2020). Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) that Result from Mutations Linked to Juvenile Myoclonic Epilepsy. CELLS, 9(3). doi:10.3390/cells9030694

2019

Fu, Z.,* Gailey, C. D., Wang, E. J., & Brautigan, D. L. (2019). Ciliogenesis associated kinase 1: targets and functions in various organ systems. FEBS LETTERS, 593(21), 2990-3002. doi:10.1002/1873-3468.13600

Oh, Y. S., Wang, E. J., Gailey, C. D., Brautigan, D. L., Allen, B. L., & Fu, Z.* (2019). Ciliopathy-Associated Protein Kinase ICK Requires Its Non-Catalytic Carboxyl-Terminal Domain for Regulation of Ciliogenesis. CELLS, 8(7). doi:10.3390/cells8070677

Bosakova, M. K., Nita, A., Gregor, T., Varecha, M., Gudernova, I., Fafilek, B., . . . Fu, Z., Krejci, P. (2019). Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(10), 4316-4325. doi:10.1073/pnas.1800338116

2018

Tong, Y., Park, S., Wu, D., Harris, T. E., Moskaluk, C. A., Brautigan, D. L., & Fu, Z.* (2018). Modulation of GSK3β autoinhibition by Thr-7 and Thr-8. FEBS LETTERS, 592(4), 537-546. doi:10.1002/1873-3468.12990

2017

Ding, M., Jin, L., Xie, L., Park, S. H., Tong, Y., Wu, D., Chhabra, A.B., Fu, Z.* & Li, X.* (2018). A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development. CALCIFIED TISSUE INTERNATIONAL, 102(3), 348-357. doi:10.1007/s00223-017-0355-3

Tong, Y., Park, S. H., Wu, D., Xu, W., Guillot, S. J., Jin, L., . . . Fu, Z.* (2017). An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome. FEBS LETTERS, 591(9), 1247-1257. doi:10.1002/1873-3468.12644

2016

Liu, J., Bolick, D. T., Kolling, G. L., Fu, Z., & Guerrant, R. L. (2016). Protein Malnutrition Impairs Intestinal Epithelial Cell Turnover, a Potential Mechanism of Increased Cryptosporidiosis in a Murine Model. INFECTION AND IMMUNITY, 84(12), 3542-3549. doi:10.1128/IAI.00705-16

2014

Bolick, D. T., Chen, T., Alves, L. A. O., Tong, Y., Wu, D., Joyner, L. T. I. I., . . . Fu, Z.* (2014). Intestinal Cell Kinase Is a Novel Participant in Intestinal Cell Signaling Responses to Protein Malnutrition. PLOS ONE, 9(9). doi:10.1371/journal.pone.0106902

2013

Chen, T., Wu, D., Moskaluk, C. A., & Fu, Z.* (2013). Distinct Expression Patterns of ICK/MAK/MOK Protein Kinases in the Intestine Implicate Functional Diversity. PLOS ONE, 8(11). doi:10.1371/journal.pone.0079359

2012

Wu, D., Chapman, J. R., Wang, L., Harris, T. E., Shabanowitz, J., Hunt, D. F., & Fu, Z.* (2012). Intestinal Cell Kinase (ICK) Promotes Activation of mTOR Complex 1 (mTORC1) through Phosphorylation of Raptor Thr-908. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(15), 12510-12519. doi:10.1074/jbc.M111.302117