Education:
PhD, Cellular Biology, University of Georgia, Athens, GA
Postdoctoral Fellowship, Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA
Clinical/Research Interests:
Primary cilia project from nearly every human cell, functioning as cellular antennas that receive and interpret signals, allowing cells to respond to their environment. These minuscule projections represent ~1/10,000th of a cell’s volume. Long thought to be vestigial organelles, we now know that loss of cilia is incompatible with human life. Dysfunctional cilia give rise to ciliopathy disorders, which exhibit overlapping clinical features, including developmental delay, intellectual disability, polydactyly, retinal dystrophy, and progressive involvement of the kidney and liver. While individually rare, ciliopathies combined affect 1/500 individuals. Most of our understanding of ciliary biology comes from model systems, such as the unicellular algae Chlamydomonas reinhardtii, as the structure of these organelles is remarkably conserved. We are interested in understanding how the complex machinery of cilia functions through the lens of cell biology and human genetics, using human cells and Chlamydomonas as models. We use ciliopathies as a platform to understand normal ciliary function and dysfunction in disease by studying 1) the function of newly identified disease-related proteins and their role in pathophysiology, 2) the underlying cellular dysfunction of ciliopathies, and 3) ciliary signaling and cascade missteps in disease. We use microscopy, proteomics, human genetics, genome engineering, and signaling pathway analysis to gain new insights into cilia biology and the mechanisms underlying disease.
Select Publications:
- Van De Weghe JC, Gomez A, and Doherty D. (2022) The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies. Annu Rev Genomics Hum Genet. Aug 31;23:301-329.
- Van De Weghe JC, Giordano JL, Mathijssen IB, Mojarrad M, Lugtenberg D, Miller CV, Dempsey JC, Mohajeri MSA, Leeuwen EV, Pajkrt E, Klaver CCW, Houlden H, Eslahi A, Waters AM, University of Washington Center for Mendelian Genomics, Bamshad MJ, Nickerson DA, Aggarwal VS, de Vries, BBA, Maroofian R, and D Doherty. (2021) TMEM218 dysfunction causes ciliopathies including Joubert and Meckel syndromes. Human Genetics and Genomic Advances. Jan 14;2(1).
- Van De Weghe JC*, Harris JA* Kubo T, Witman GB, and Lechtreck KF. (2020) Diffusion rather than IFT likely provides most of the tubulin required for axonemal assembly. Journal of Cell Science. Sept 11;133(17):jcs249805.
- Latour BL*, Van De Weghe JC*, Rusterholz TDS*, Letteboer SJF, Gomez A, Shaheen R, Gesemann M, Karamzade A, Asadollahi M, Barroso-Gil M, Chitre M, Grout ME, Reeuwijk JV, Beersum SECV, Miller CV, Dempsey JC, Morsy H, University of Washington Center for Mendelian Genomics, Bamshad MJ, Genomics England Research Consortium, Nickerson DA, Neuhauss SCF, Boldt K, Ueffing M, Keramatipour M, Sayer JA, Alkuraya FS, Bachmann-Gagescu R, Roepman R, and Doherty D. (2020) Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. Journal of Clinical Investigation. July 20;131656.
- Van De Weghe JC*, Rusterholz T*, Latour B*, Grout M, Aldinger K, Shaheen R, Dempsey J, Maddirevula S, Cheng Y, Phelps I, Gesemann M, Goel H, Birk O, Alanzi T, Rawashdeh R, Khan A, University of Washington Center for Mendelian Genomics, Bamshad M, Nickerson D, Neuhauss S, Dobyns W, Alkuraya F, Roepman R, Bachmann-Gagescu, R, and Dan Doherty. (2017) Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome in humans and ciliopathy phenotypes in zebrafish. American Journal of Human Genetics. July 6;101(1)23-36.
- Shi X, Garcia III G, Van De Weghe JC, McGorty R, Pazour G, Doherty D, Huang B, and Reiter JF. (2017) Super-resolution microscopy reveals that disruption of ciliary transition zone architecture causes Joubert syndrome. Nature Cell Biology. Oct;19(10):1178-1188.
*shared first author
NCBI My Bibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/1j7XeR0mjzy5h/bibliography/43221658/public/?sdirection=descending&sortby=pubDate