# Centrosome regulation of trafficking, ciliogenesis and cilia-dependent signaling

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $306,408

## Abstract

PROJECT SUMMARY / ABSTRACT
Centrosomes are the central organizing centers of cells, performing essential functions for mitotic spindles and
cilia. Diverse human diseases arise from defects to centrosomes because they impact both mitotic and ciliary
functions. We discovered that cells from individuals with Down syndrome have both defective centrosomes and
cilia. This opens an important new avenue for understanding the cell biological basis of Down syndrome.
Because primary cilia loss is developmentally lethal, our studies will explore the role that subtle changes to
centrosomes have in controlling cilia formation and function. Central to the reduced cilia function in Trisomy 21
cells, we discovered that elevated expression of the Pericentrin gene, encoded on chromosome 21, is
necessary and sufficient to repress the movement of components required for both cilia formation and function
from the cytoplasm to the centrosome and cilium. Pericentrin is a centrosome and intracellular trafficking
scaffold protein that dramatically increases and decreases during the cell cycle, with levels lowest when cilia
formation occurs and highest during mitosis. We propose that exquisite control of Pericentrin ensures cilia
formation and function. However, we do not understand why the modest 1.5-fold increase in Pericentrin protein
found in Down syndrome has such a profound impact on cilia. We will test how decreased and increased
Pericentrin levels impact centrosomes, the interphase microtubule landscape, and satellite and vesicular
trafficking, and what the consequent outcomes for cilia formation and signaling are. Excellent training
opportunities exist for undergraduate and graduate students and postdoctoral researchers in the Pearson lab.
We will continue to use and develop our rigorous training and experimental routines in alignment with the NIH
guidelines for increasing rigor and reproducibility. Collaborations with other labs that specialize in electron
microscopy and machine learning quantitative analyses will expand the innovation and impact of our studies of
intracellular trafficking. In summary, this proposal will illuminate how the precise control of the human disease
protein, Pericentrin, is coordinated with the cell cycle to ensure proper primary cilia formation and signaling
required for normal development. This application aims to elucidate fundamental cell biological events in
intracellular trafficking, cilia formation and cilia-dependent signaling that are commonly defective in human
disease.

## Key facts

- **NIH application ID:** 10028106
- **Project number:** 1R01GM138415-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** CHAD G PEARSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $306,408
- **Award type:** 1
- **Project period:** 2020-08-14 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028106

## Citation

> US National Institutes of Health, RePORTER application 10028106, Centrosome regulation of trafficking, ciliogenesis and cilia-dependent signaling (1R01GM138415-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10028106. Licensed CC0.

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