I earned a B.S. degree in Biochemistry from Lehman College in 1996, and a Ph.D. in 2005 from Stony Brook University, followed by postdoctoral research at Harvard University in the laboratory of Dr. Joshua Sanes. In 2012, I accepted a position as Assistant Professor at Virginia Polytechnic Institute (Virginia Tech) where I was promoted to Associate Professor, with tenure, in 2018.
In 2019, I moved to Brown University to join the Department of Molecular Biology, Cell Biology and Biochemistry in the Division of Biology and Medicine, and the Center for Translational Neuroscience.
I am a neuroscientist and a skeletal muscle biologist. My research is primarily focused on discovering 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 all, my scientific contributions have implications for mitigating the negative health effects of normal aging and treating age-related neurological diseases such as ALS and Alzheimer’s disease.
|Zeitz MJ, Calhoun PJ, James CC, Taetzsch T, George KK, Robel S, Valdez G, Smyth JW. "Dynamic UTR Usage Regulates Alternative Translation to Modulate Gap Junction Formation during Stress and Aging." Cell Reports, vol. 27, no. 9, 2019, pp. 2737-2747.e5.|
|Valdez G. "Effects of disease-afflicted and aging neurons on the musculoskeletal system." Bone, vol. 122, 2019, pp. 31-37.|
|Magalhães-Gomes MPS, Motta-Santos D, Schetino LPL, Andrade JN, Bastos CP, Guimarães DAS, Vaughan SK, Martinelli PM, Guatimosim S, Pereira GS, Coimbra CC, Prado VF, Prado MAM, Valdez G, Guatimosim C. "Fast and slow-twitching muscles are differentially affected by reduced cholinergic transmission in mice deficient for VAChT: A mouse model for congenital myasthenia." Neurochemistry international, vol. 120, 2018, pp. 1-12.|
|Taetzsch T, Brayman VL, Valdez G. "FGF binding proteins (FGFBPs): Modulators of FGF signaling in the developing, adult, and stressed nervous system." Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1864, no. 9 Pt B, 2018, pp. 2983-2991.|
|Taetzsch T, Valdez G. "NMJ maintenance and repair in aging." Current opinion in physiology, vol. 4, 2018, pp. 57-64.|
|Herskovits AZ, Hunter TA, Maxwell N, Pereira K, Whittaker CA, Valdez G, Guarente LP. "SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis." Aging Cell, vol. 17, no. 6, 2018, pp. e12839.|
|Vaughan SK, Sutherland NM, Zhang S, Hatzipetros T, Vieira F, Valdez G. "The ALS-inducing factors, TDP43<sup>A315T</sup> and SOD1<sup>G93A</sup>, directly affect and sensitize sensory neurons to stress." Scientific reports, vol. 8, no. 1, 2018, pp. 16582.|
|Maxwell N, Castro RW, Sutherland NM, Vaughan KL, Szarowicz MD, de Cabo R, Mattison JA, Valdez G. "α-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and mice." Aging Cell, vol. 17, no. 2, 2018.|
|Stockinger J, Maxwell N, Shapiro D, deCabo R, Valdez G. "Caloric Restriction Mimetics Slow Aging of Neuromuscular Synapses and Muscle Fibers." The Journals of Gerontology: Series A, vol. 73, no. 1, 2017, pp. 21-28.|
|Vaughan SK, Stanley OL, Valdez G. "Impact of Aging on Proprioceptive Sensory Neurons and Intrafusal Muscle Fibers in Mice." The Journals of Gerontology: Series A, vol. 72, no. 6, 2017, pp. 771-779.|
|Li P, Fu X, Smith NA, Ziobro J, Curiel J, Tenga MJ, Martin B, Freedman S, Cea-Del Rio CA, Oboti L, Tsuchida TN, Oluigbo C, Yaun A, Magge SN, O'Neill B, Kao A, Zelleke TG, Depositario-Cabacar DT, Ghimbovschi S, Knoblach S, Ho CY, Corbin JG, Goodkin HP, Vicini S, Huntsman MM, Gaillard WD, Valdez G, Liu JS. "Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy." Neuron, vol. 96, no. 2, 2017, pp. 387-401.e6.|
|Taetzsch T, Tenga MJ, Valdez G. "Muscle Fibers Secrete FGFBP1 to Slow Degeneration of Neuromuscular Synapses during Aging and Progression of ALS." Journal of Neuroscience, vol. 37, no. 1, 2017, pp. 70-82.|
|Dalkin W, Taetzsch T, Valdez G. "The Fibular Nerve Injury Method: A Reliable Assay to Identify and Test Factors That Repair Neuromuscular Junctions." Journal of visualized experiments : JoVE, no. 114, 2016.|
|Sugita S, Fleming LL, Wood C, Vaughan SK, Gomes MP, Camargo W, Naves LA, Prado VF, Prado MA, Guatimosim C, Valdez G. "VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions." Skeletal Muscle, vol. 6, 2016, pp. 31.|
|Vaughan SK, Kemp Z, Hatzipetros T, Vieira F, Valdez G. "Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations." The Journal of comparative neurology, vol. 523, no. 17, 2015, pp. 2477-94.|
|Dittmar WJ, McIver L, Michalak P, Garner HR, Valdez G. "EvoCor: a platform for predicting functionally related genes using phylogenetic and expression profiles." Nucleic acids research, vol. 42, no. Web Server issue, 2014, pp. W72-5.|
|Valdez G, Heyer MP, Feng G, Sanes JR. "The role of muscle microRNAs in repairing the neuromuscular junction." PLoS ONE, vol. 9, no. 3, 2014, pp. e93140.|
|Samuel MA, Valdez G, Tapia JC, Lichtman JW, Sanes JR. "Agrin and synaptic laminin are required to maintain adult neuromuscular junctions." PLoS ONE, vol. 7, no. 10, 2012, pp. e46663.|
|Valdez G, Tapia JC, Lichtman JW, Fox MA, Sanes JR. "Shared resistance to aging and ALS in neuromuscular junctions of specific muscles." PLoS ONE, vol. 7, no. 4, 2012, pp. e34640.|
|Philippidou P, Valdez G, Akmentin W, Bowers WJ, Federoff HJ, Halegoua S. "Trk retrograde signaling requires persistent, Pincher-directed endosomes." Proceedings of the National Academy of Sciences, vol. 108, no. 2, 2011, pp. 852-7.|
|Valdez G, Tapia JC, Kang H, Clemenson GD Jr, Gage FH, Lichtman JW, Sanes JR. "Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise." Proceedings of the National Academy of Sciences, vol. 107, no. 33, 2010, pp. 14863-8.|
|Carlson SS, Valdez G, Sanes JR. "Presynaptic calcium channels and α3-integrins are complexed with synaptic cleft laminins, cytoskeletal elements and active zone components." Journal of neurochemistry, vol. 115, no. 3, 2010, pp. 654-66.|
|Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, Bassel-Duby R, Sanes JR, Olson EN. "MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice." Science, vol. 326, no. 5959, 2009, pp. 1549-54.|
|Proszynski TJ, Gingras J, Valdez G, Krzewski K, Sanes JR. "Podosomes are present in a postsynaptic apparatus and participate in its maturation." Proceedings of the National Academy of Sciences, vol. 106, no. 43, 2009, pp. 18373-8.|
|Bonanomi D, Fornasiero EF, Valdez G, Halegoua S, Benfenati F, Menegon A, Valtorta F. "Identification of a developmentally regulated pathway of membrane retrieval in neuronal growth cones." Journal of cell science, vol. 121, no. Pt 22, 2008, pp. 3757-69.|
|Nishimune H, Valdez G, Jarad G, Moulson CL, Müller U, Miner JH, Sanes JR. "Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction." The Journal of cell biology, vol. 182, no. 6, 2008, pp. 1201-15.|
|Valdez G, Philippidou P, Rosenbaum J, Akmentin W, Shao Y, Halegoua S. "Trk-signaling endosomes are generated by Rac-dependent macroendocytosis." Proceedings of the National Academy of Sciences, vol. 104, no. 30, 2007, pp. 12270-5.|
|Valdez G, Akmentin W, Philippidou P, Kuruvilla R, Ginty DD, Halegoua S. "Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors." Journal of Neuroscience, vol. 25, no. 21, 2005, pp. 5236-47.|
|Kuruvilla R, Zweifel LS, Glebova NO, Lonze BE, Valdez G, Ye H, Ginty DD. "A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling." Cell, vol. 118, no. 2, 2004, pp. 243-55.|
|Wang S, Liu Y, Adamson CL, Valdez G, Guo W, Hsu SC. "The mammalian exocyst, a complex required for exocytosis, inhibits tubulin polymerization." Journal of Biological Chemistry, vol. 279, no. 34, 2004, pp. 35958-66.|
|Shao Y, Akmentin W, Toledo-Aral JJ, Rosenbaum J, Valdez G, Cabot JB, Hilbush BS, Halegoua S. "Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes." The Journal of cell biology, vol. 157, no. 4, 2002, pp. 679-91.|
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
Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular
The goal of this project is to determine the interplay between FGFBP1 and TGF-beta in slowing degeneration of NMJs caused by normal aging.
R21NS106313 (PI: Valdez) 05/15/2018 – 04/30/2020
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.
R56AG051501 (PI: Valdez) 09/30/2017 – 08/31/2019
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.
Department of Neurology
Center for Translational Neuroscience
|BIOL 0500 - Cell and Molecular Biology|
|BIOL 2340 - Neurogenetics and Disease|