Advising Statement: Here
The aim of our laboratory is to understand the molecular pathways that drive protein aggregation and neuronal death in Huntington´s Disease (HD), an inherited neurodegenerative disease characterized by severe motor and cognitive decline. We examine the role of Heat Shock Factor (HSF1), a transcription factor that regulates protein folding, inflammation, and apoptosis. We apply molecular biology, biochemistry, neuroanatomy, and imaging to different HD cellular and mouse models as well as human specimens. Our final goal is to provide new therapeutic strategies to prevent neuronal death and improve ameliorate disease symptoms.
Lab web page: gomez-pastor-lab.neuroscience.umn.edu
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Front Cell Neurosci. 2023 Apr 28;17:1094503. Striatal spatial heterogeneity, clustering, and white matter association of GFAP+ astrocytes in a mouse model of Huntington's disease.
- Cell Rep. 2023 Mar 2;42(3):112198. Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington's disease
- Adv Exp Med Biol. 2022 Nov 18. doi: 10.1007/5584_2022_742. HSF1 and its role in Huntington's Disease pathology.
- Zarate N, Gundry K, Yu D, Casby J, Eberly LE, Öz G, Gomez-Pastor R. Neurochemical correlates of synapse density in a Huntington's disease mouse model. J Neurochem. 2023 Jan;164(2):226-241.
- Yu D, Zarate N, White A, Coates D, Tsai W, Nanclares C, Cuccu F, Yue JS, Brown TG, Mansky RH, Jiang K, Kim H, Nichols-Meade T, Larson SN, Gundry K, Zhang Y, Tomas-Zapico C, Lucas JJ, Benneyworth M, Öz G, Cvetanovic M, Araque A, Gomez-Pastor R. CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease. Acta Neuropathol Commun. 2022 Jun 3;10(1):83. Erratum in: Acta Neuropathol Commun. 2022 Jun 22;10(1):89.
- Zarate N, Intihar TA, Yu D, Sawyer J, Tsai W, Syed M, Carlson L, Gomez-Pastor R. Heat shock factor 1 directly regulates postsynaptic scaffolding PSD-95 in aging and Huntington's disease and influences striatal synaptic density. Int J Mol Sci. 2021 Dec 4;22(23):13113.
- Burchfiel ET, Vihervaara A, Guertin MJ, Gomez-Pastor R, Thiele DJ. Comparative interactomes of HSF1 in stress and disease reveal a role for CTCF in HSF1-mediated gene regulation. J Biol Chem. 2021 Jan-Jun;296:100097.
- Zarate N, Gomez-Pastor R. Excitatory synapse impairment and mitochondrial dysfunction in Huntington's disease: heat shock factor 1 (HSF1) converging mechanisms. Neural Regen Res. 2020 Jan;15(1):69-70.
- Liu P, Smith BR, Huang ES, Mahesh A, Vonsattel JPG, Petersen AJ, Gomez-Pastor R, Ashe KH. A soluble truncated tau species related to cognitive dysfunction and caspase-2 is elevated in the brain of Huntington's disease patients. Acta Neuropathol Commun. 2019 Jul 30;7(1):111.
- Intihar TA, Martinez EA, Gómez-Pastor R. Mitochondrial dysfunction in Huntington's Disease; Interplay between HSF1, p53 and PGC-1α transcription factors. Front Cell Neurosci. 2019 Mar 19;13:103.
- Gómez-Pastor R, Burchfiel ET, Thiele DJ. Regulation of heat shock transcription factors and their roles in physiology and disease. Nat Rev Mol Cell Biol. 2018 Jan;19(1):4-19.
- Gómez-Pastor R, Burchfiel ET, Neef DW, Jaeger AM, Cabiscol E, McKinstry SU, Doss A, Aballay A, Lo DC, Akimov SS, Ross CA, Eroglu C, Thiele DJ. Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington's disease. Nat Commun. 2017 Feb 13;8:14405.
- Neef DW, Jaeger AM, Gómez-Pastor R, Willmund F, Frydman J, Thiele DJ. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 2014;9(3):955-966.
- Casani S, Gómez-Pastor R, Matallana E, Paricio N. Antioxidant compound supplementation prevents oxidative damage in a Drosophila model of Parkinson's disease. Free Radic Biol Med. 2013;61:151-160.
- Lavara-Culebras E, Muñoz-Soriano V, Gómez-Pastor R, Matallana E, Paricio N. Effects of pharmacological agents on the lifespan phenotype of Drosophila DJ-1beta mutants. Gene. 2010;462(1-2):26-33.
Current Graduate Students:
Taylor Brown (Neuroscience, University of Minnesota).
Angel White (Neuroscience, University of Minnesota).
Former Graduate Students:
Nicole Zarate (Neuroscience, University of Minnesota).