Fu, Zheng "John"
Primary Appointment
Associate Professor, Pharmacology
Education
- BS, Molecular Biology, NanKai University, Tianjin, P. R. China
- PhD, Cell and Developmental Biology, University of Florida, Gainesville, FL
Contact Information
1340 JPA, Pinn Hall 5217
PO Box 800735
Charlottesville, VA 22908-0708
Telephone: 434-982-3204
Email: zf6n@virginia.edu
Research Disciplines
Biochemistry, Cancer Biology, Cell and Developmental Biology
Research Interests
Molecular basis of ciliopathies; Signaling mechanisms of cilia-associated kinases
Research Description
Our 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.