Randal Tibbetts
Credentials: Human Oncology Department
Position title: DNA repair; RNA splicing; neurodegeneration; amyotrophic lateral sclerosis
Email: rstibbetts@wisc.edu
Phone: (608) 262-0027
Address:
3059 Wi Institute Medical Research
1111 Highland Ave
Madison, WI 53705
LAB WEBSITE:
FOCUS GROUPS:
Cancer Biology; Developmental Biology & Regenerative Medicine; RNA Biology
RESEARCH DESCRIPTION:
Current work in the Tibbetts lab is focused on two major themes: (i) genetic and biochemical mechanisms of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD); and (ii) The role of alternative splicing in DNA damage repair and tumor suppression. ALS/FTD-related studies are focused on several genes, including the gene encoding the ubiquitin-binding protein, UBQLN2 whose mutation cause inherited forms of ALS/FTD. We employ a “fly-to-human” approach in which genetic screens are first used to identify novel genes that modify the toxicity of ALS/FTD-associated proteins in the fruit fly, Drosophila melanogaster. These genes are then studied at the mechanistic level using human inducible pluripotent stem cell (iPSC)-derived motor neurons and gene edited mice containing mutations in ALS/FTD-associated genes. Using this strategy we have identified several disease-modifier genes, including axon guidance genes and regulators of endolysosomal function, which are being investigated for therapeutic potential in preclinical ALS/FTD models. These studies will employ cutting edge transcriptomic and proteomic approaches to understand how ALS/FTD-causal mutations instigate neurodegeneration at the cellular level. In a second project we are investigating how alternative splicing of the DNA repair gene RIF1 influences its participation in DSB repair and genome stabilization using both cell culture and mouse models.
ALSO A TRAINER IN THE FOLLOWING PROGRAMS:
Genetics; Molecular and Cellular Pharmacology Training Program (MCP); Cancer Biology Training Program