The goal of my research is to discover molecules that function to preserve and restore the function of the nervous system and skeletal muscles during normal aging and affected with age-related diseases. Over the years, I have identified molecules that function to slow degeneration of the synapse motor neurons and skeletal muscles form, called the neuromuscular junction (NMJ) during aging as well as in amyotrophic lateral sclerosis (ALS), an age-associated disease. I have also co-discovered molecules important for the formation and maintenance of brain synapses. In ongoing projects, my lab continues to examine the contribution of molecular mechanisms and unique cell types discovered in my lab to synaptic maintenance and repair. 

In addition to relaying information, synapses are critical for the maintenance and survival of connected cells. Hence, it is not surprising that malfunction and degeneration of synapses impair cognatic and motor function. The primary focus of my research is to uncover the functional, morphological and molecular changes that occur in lower motor neurons, skeletal muscles and synapses with advancing age and neurological diseases. For this, we deploy behavioral, cellular, molecular and electrophysiological analysis. We have shown that loss of a secreted factor (FGFBP1) and modulator of FGF-signaling contributes to synaptic degeneration during aging and progression of ALS. My lab has also shown that sensory nerve endings degenerate early and progressively with advancing age and in ALS. Additionally, we have discovered that small yet persistent changes in the cholinergic system result in pathophysiological features associated with aging and ALS.

My lab is currently in the midst of several ongoing and exiting projects that include: 1) assessing the role of the RNA-induced silencing complex (RISC) in synaptic degeneration with advancing age and progression of ALS pathogenesis; 2) targeting the cholinergic system to preserve motor function into old age; 3) analyzing a specialized population of glial cells at NMJs and in the brain; and 4) determining the effect of aging on spinal cord synaptic inputs critical for voluntary movements. These projects have broad implications for preserving and repairing damages in neuronal circuits and skeletal muscles caused by aging, injuries, Alzheimer’s disease, ALS, and other age-related diseases.  

R01AG055545 (PI: Valdez)                                                                                         04/15/2017 – 03/31/2022

NIH/NIA

Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular

Junctions

The goal of this project is to determine the interplay between FGFBP1 and TGF-beta in slowing degeneration of NMJs caused by normal aging.

Role: PI

R21NS106313 (PI: Valdez)                                                                                         05/15/2018 – 04/30/2020

NIH/NINDS

Analysis of sensory neurons to understand and identify factors to treat ALS

The goal of this project is to determine if sensory neurons expressing mutant genes that cause ALS can be used in culture to identify and test therapeutic for the diseases.

Role: PI

R56AG051501 (PI: Valdez)                                                                                         09/30/2017 – 08/31/2019

NIH/NIA                                                                                                                                                         NCE

Dysregulated cholinergic transmission contributes to aging of the lower motor system

This goal of this project is to determine the adverse consequences of long-term altering cholinergic transmission on the stability of neuromuscular junctions and skeletal muscles. 

Molecular Biology, Cell Biology and Biochemistry

Department of Neurology

Center for Translational Neuroscience