Jeremy Reiter, MD, PhD

Professor and Chair
Department of Biochemistry and Biophysics
+1 415 476-0156
Research Overview: 

Eukaryotic cilia and flagella are cellular structures familiar to schoolchildren everywhere for the elegant swath they cut as they propel protozoa through pond water. Less well recognized is the fact that a single immotile cilium is present on almost every type of vertebrate cell. These so-called primary cilia were discovered more than a century ago and, yet, their functions remain largely unexplored (Singla and Reiter, 2006).

It is now becoming clear that the primary cilium plays important roles in both development and disease. Perhaps its most dramatic function is in the kidney - ciliary defects cause polycystic kidney disease, the most common life-threatening monogenic illness. Primary cilia also have roles in sensing environmental information. Photoreceptors and odorant receptors function on primary cilia, and primary cilia are essential for sound reception. Therefore, it is not much of an exaggeration to say that we see, smell and hear through cilia.

Our work suggests that cilia also function as critical mediators of intercellular signals during development (Corbit et al., 2005; May et al., 2005; Reiter and Skarnes, 2006). One crucial role is in the coordination of the Hedgehog signal transduction pathway. Hedgehog signals are essential regulators of embryonic patterning and cell proliferation, and defects in Hedgehog signaling are important causes of both birth defects and many cancers. We are currently extending this work by asking a few fundamental questions about primary cilia:

  • Do cilia transduce intercellular signals other than Hedgehog?
  • How do cilia interpret signals essential to vertebrate development?
  • Do cilia participate in Hedgehog-mediated oncogenesis?
  • How do cells regulate whether they form a cilium?

This work has begun to suggest that the primary cilium is an organelle dedicated to signal transduction, somewhat analogous to a cellular antenna. We hope that our current endeavors will reveal how this antenna interprets the signals required for normal development and homeostasis, and how malfunctions in the antenna contribute to cancer and other important human diseases.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Signaling at the Primary Cilium, the Cell's Antenna

Websites

Publications: 

Emerging mechanistic understanding of cilia function in cellular signalling.

Nature reviews. Molecular cell biology

Hilgendorf KI, Myers BR, Reiter JF

GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.

Nature structural & molecular biology

Hoppe N, Harrison S, Hwang SH, Chen Z, Karelina M, Deshpande I, Suomivuori CM, Palicharla VR, Berry SP, Tschaikner P, Regele D, Covey DF, Stefan E, Marks DS, Reiter JF, Dror RO, Evers AS, Mukhopadhyay S, Manglik A

ADPKD-Causing Missense Variants in Polycystin-1 Disrupt Cell Surface Localization or Polycystin Channel Function.

bioRxiv : the preprint server for biology

Ha K, Loeb GB, Park M, Pinedo A, Park CH, Brandes N, Ritu F, Ye CJ, Reiter JF, Delling M

Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.

Cell reports

Hoi KK, Xia W, Wei MM, Ulloa Navas MJ, Garcia Verdugo JM, Nachury MV, Reiter JF, Fancy SPJ

Polycystin-2 dependent transcriptome reveals early response of autosomal dominant polycystic kidney disease.

Physiological genomics

Jung HJ, Dixon EE, Coleman R, Watnick T, Reiter J, Outeda P, Cebotaru V, Woodward OM, Welling PA