Anita Bhattacharyya, PhD
Principal Investigator
Waisman Center
University of Wisconsin at Madison

FRAXA Awards:
  $60,000 in 2008 
  $35,000 in 2007
  $30,000 in 2006

by Anita Bhattacharyya, updated 4/2007

Fragile X syndrome is defined by the loss of fragile X mental retardation protein (FMRP). It is important to determine how cellular processes are affected by the loss of FMRP in human brain cells, both to learn more about the symptoms of the disorder and to establish pathways to target for potential therapeutics.

Cells respond to signals (e.g. electrical, chemical signals) by signal transduction cascades that relay information from the outside of the cell to the nucleus where changes in genes occur. We want to test how the loss of FMRP affects a neural cell's signal transduction cascades. One signal transduction relay molecule that has been implicated in Fragile X is cyclic AMP (cAMP). Previous work by Fragile X researcher Elizabeth Berry-Kravis and colleagues showed that cAMP is lower in blood cells from Fragile X individuals. We have now found that cells of the nervous system are also not able to produce cAMP as well in Fragile X. Lowered cAMP signal transduction affects how FX cells in the brain respond to stimuli and how they function during development and during plasticity.

In this project, we want to understand why cAMP production is lower in Fragile X. How does the lack of FMRP cause lower cAMP signaling? We also want to figure out whether there is a link between defective cAMP production and another signal transduction cascade linked to FX, the mGluR pathway. Finally, using a drug assay on human FX cells, we hope to find compounds that can rescue the cAMP defect in FX cells.