Anatomy and Cell Biology
PhD: 2002, McGill University, Montreal, Canada
Postdoctoral Fellow: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Instructor: Harvard Medical School, Boston, MA
Our research focuses on the role of the primary cilium in developmental signaling and disease. The primary cilium is a slender extension of the plasma membrane present on most vertebrate cells that acts as a sensory organelle and mediates signaling pathways. Ciliary defects are linked to a growing class of human syndromic disorders termed ciliopathies, which manifest common illnesses such as cystic kidney disease, retinal degeneration and obesity as major clinical components. Yet the molecular events connecting ciliary dysfunction to disease remain unclear.
We have identified a novel ciliary protein, THM1 (TPR-containing Hedgehog modulator 1; also termed Ttc21b or IFT139), which negatively regulates Hedgehog (Hh) signaling. In mouse, genetic deletion of Thm1 during late embryogenesis results in renal cysts and retinal defects, while ablation of Thm1 during adulthood leads to increased body weight and overall growth. To bridge the molecular gap between ciliary defect and disease, our investigations are two-fold:
THM1 (green) localizes in a punctate fashion from base to tip of cilium. Tubulin (red) marks the ciliary core or axoneme.
Loss of THM1 in alien (aln) mutant mouse results in shorter cilia with bulb-like structures at the distal tip.
Loss of THM1 in aln mutant mouse embryo (E9.5) results in upregulation of Patched1 (Ptch1) expression, a marker of Hh signaling.
Left to right: Damon Jacobs PhD (Postdoctoral Fellow), Pamela Tran PhD (PI), Michael Peter Schonfeld MSc (Lab Manager).
ASN Carl W. Gottschalk Research Scholar Award