Understanding Chemotherapy-Induced Peripheral Neuropathy Mechanisms using CRISPRi and Chemical Screens in Human iPSC-Derived Sensory Neurons
Grant Award Details
Grant Type:
Grant Number:
DISC0-14357
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,621,913
Status:
Active
Grant Application Details
Application Title:
Understanding Chemotherapy-Induced Peripheral Neuropathy Mechanisms using CRISPRi and Chemical Screens in Human iPSC-Derived Sensory Neurons
Public Abstract:
Research Objective
The research objectives are to identify causal genes for chemotherapy-induced mitochondrial toxicity and neurodegeneration in sensory neurons and drugs that target this toxicity.
Impact
These studies will open the possibility for genetic or drug targeting to prevent and treat drug-induced peripheral neuropathies and possibly neuropathies caused by disease or inherited.
Major Proposed Activities
The research objectives are to identify causal genes for chemotherapy-induced mitochondrial toxicity and neurodegeneration in sensory neurons and drugs that target this toxicity.
Impact
These studies will open the possibility for genetic or drug targeting to prevent and treat drug-induced peripheral neuropathies and possibly neuropathies caused by disease or inherited.
Major Proposed Activities
- Perform genome-wide CRISPRi screens in human iPSC-derived sensory neurons to identify critical genes and pathways for mitochondrial toxicity associated with microtubule targeting agents.
- Perform a screen of 1600 small molecule drugs in iPSC-derived sensory neurons to identify drugs and therapeutic targets that attenuate the neurodegeneration induced by microtubule targeting agents.
Statement of Benefit to California:
California has a large population of cancer patients, many of whom suffer from debilitating adverse events from their cancer therapies. These studies seek to increase our knowledge about the causes of one common toxicity, peripheral neuropathy, and to identify potential genes and pathways that can be targeted for its prevention or treatment. The successful completion of these studies could improve the quality of life for cancer patients in California.