Sensing and responding to the environment is critical for all living beings. Most sensory systems utilize cilia to sense stimuli and convert them into physiological responses.
Jinghua Hu, Ph.D., uses various model systems to study the correlation between cilia dysfunction and cilia-related diseases (collectively known as ciliopathies). The long-term goals of Dr. Hu's laboratory are to understand how cilia form and function; determine the pathogenesis underlying ciliopathies; and design therapies to prevent, delay or halt disease progression.
With rapid advancements during the past decade in the positional cloning of human disease genes, a wide variety of genetic disorders — such as autosomal dominant polycystic kidney disease (ADPKD), Bardet-Biedl syndrome, Joubert syndrome, nephronophthisis, Meckel-Gruber syndrome and autosomal recessive polycystic kidney disease — have been molecularly characterized as ciliopathies.
Because of the essential role of mammalian cilia in embryonic development, it is prohibitively difficult to study the functions of ciliopathy candidates in mammalian models. The highly conserved ciliopathy genes, ciliogenesis pathway and cilia sensory function of C. elegans make this organism a powerful model for characterizing the physiological roles of ciliary proteins in their native cellular environment.
The major experimental approaches used in Dr. Hu's laboratory include molecular genetics, biochemistry, real-time imaging and model organisms. Dr. Hu's research has been funded by the National Institutes of Health and PKD Foundation, among other organizations.
- Characterization of known ciliopathy causal loci. Consistent with the ubiquitous presence of cilia on the surfaces of most cells in the human body, most ciliopathies occur as syndromic disorders that affect the homeostasis of many organs during development, including the kidneys, liver, limbs, eyes, central nervous system and fat storage tissue.
Despite the physiological and clinical relevance of cilia, the molecular mechanisms that regulate cilia formation and function and the connections between disease gene functions and pathology remain largely elusive. Genes being studied in Dr. Hu's laboratory include polycystins (mutated in ADPKD), BBS proteins (mutated in Bardet-Biedl syndrome), ARL13B (mutated in Joubert syndrome); MKSs (mutated in Meckel-Gruber syndrome), and NPHPs (mutated in nephronophthisis).
- Discovery of new ciliopathy causal loci. Whole-genome screens are performed in C. elegans to search for the genes involved in cilia formation and cilia function. In collaboration with the state-of-the-art human genetics lab at Mayo Clinic, the human homologs of identified candidates will be sequenced in ciliopathy patients with unknown causal loci.
Significance to patient care
Dr. Hu's research will advance our knowledge about the pathogenesis of ciliopathies; discover new causal loci; and help design therapies to prevent, delay or halt disease progression.
- Co-Director, Model Systems Core, Mayo Translational PKD Center