Post Type Description
A major hallmark of ALS pathology is incorrect localisation of a protein called TDP-43. When in the incorrect location TDP-43 can initiate degeneration of brain cells. This project aims to dissect whether this toxicity depends on three different capabilities of…
Dysregulation of RNA metabolism is a defining feature of ALS, resulting from the nuclear clearance of the RNA-binding protein TDP-43. TDP-43 is known to bind to its target pre-mRNAs near polyadenylation signals; however, this key aspect of TDP-43 function has…
The Kao Lab is interested in the basic mechanisms driving development of neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and Alzheimer’s Disease (AD). Our work has led us to focus specifically on the lysosome, a part of the cell responsible…
Over the past few decades, researchers have made great strides in understanding how certain genetic mutations can lead to ALS. However, most patients do not present with these mutations, and it is often difficult to predict whether our understanding of…
Stress has been implicated in neurodegenerative disease pathogenesis. This research aims to elucidate the normal role of ALS-linked proteins in responding to and mitigating stress, as well to determine whether this role becomes dysfunctional in disease.
In ALS, ocular motor neurons are more resistant to degeneration than other upper and lower motor neurons. Microglia, the immune cells of the brain can elicit both neuroprotective and neurotoxic effects and thus influence neuronal degeneration. In this project, we…
TDP-43 is an RNA binding protein linked to the majority of ALS cases, that has been shown to alter the localization and translation of target mRNAs in motor neurons. Here we will use genetic and biochemical approaches to investigate the…
In the vast majority of ALS cases a protein called TDP-43 forms clumps in deteriorating neurons. In the proposed studies, we will explore how a natural polymer, poly(ADP-ribose), enables TDP-43 clumping. We will also define optimal drugs to antagonize poly(ADP-ribose)…
Mutations in the gene NEK1 are major contributors to ALS. The mechanisms by which these mutations impair the function of the NEK1 protein and cause the degeneration of motor neurons in ALS patients remain unclear. The goal of this study…
A major impediment to clinical trials of potentially disease-modifying therapies for ALS has been the lack has been a lack of robust biomarkers of disease-relevant neuronal dysfunction. Loss of function of TDP-43 is now recognized as an early and defining…
