Dr. David Borchelt
Dedicated to gaining a better understanding of the molecular mechanisms underlying Alzheimer’s disease and related disorders.
Director, Center for Translation Research in Neurodegenerative Disease
Director, SantaFe Health Alzheimer’s Disease Research Center;
Professor. Department of Neuroscience
Investigator, Evelyn F, and William L McKnight Brain Institute
PhD, Microbiology/Virology, Univ. of Kentucky, 1986
MS, Microbiology, Univ. of Kentucky, 1984
BS, Biology, Univ. of Kentucky, 1979
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Research Focus and Aims
Over the past several years there has been tremendous progress in identifying the gene products that mediate a number of neurodegenerative disorders, including familial Alzheimer’s disease, familial amyotrophic lateral sclerosis, and Huntington’s disease. These disorders are all progressive, fatal disorders that result from the dysfunction and death of specific populations of nerve cells. In all of these disorders, a change in the amino acid sequence of specific proteins initiates a cascade of events that lead to disease. A common feature of these disorders is the accumulation of misfolded proteins or peptides in regions of the CNS affected by each disease. My laboratory is committed to investigations designed to elucidate the molecular processes by which specific mutant proteins cause disease. This work involves the use of transgenic mouse models, knockout mice, and cell culture systems to examine the effect of mutations on the function and biology of the mutated proteins. Collectively, these approaches provide insight into the molecular mechanisms of disease and have the potential to identify new therapeutic strategies for these disorders.
- Moloney C, Rayaprolu S, Howard J, Fromholt S, Brown H, Collins M, Cabrera M, Duffy C, Siemienski Z, Miller D, Swanson MS, Notterpek L, Borchelt DR, Lewis J. Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype. Acta Neuropathol. Commun. 4:122, 2016, PMID:27863507, PMC5116203.
- Ayers JI, Diamond J, Sari A, Fromholt S, Galaleldeen A, Ostrow LW, Glass JD, Hart PJ, Borchelt DR. Distinct conformers of transmissible misfolded SOD1 distinguish human SOD1-FALS from other forms of familial and sporadic ALS. Acta Neuropathol. 132:827-840, 2016, PMID:27704280.
- Xu G, Pattamatta A, Hildago R, Pace MC, Brown H, Borchelt DR. Vulnerability of newly synthesized proteins to proteostasis stress. J. Cell Sci.129:1892-1901, 2016. PMID:27026526. PMC4893652.
- Ayers JI, Fromholt SE, O’Neal VM, Diamond JH, Borchelt DR. Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways. Acta Neuropathol. 131:103-114, 2016. PMID: 26650262. PMC4699876.
- Gallego-Iradi MC, Clare AM, Brown HH, Janus C, Lewis J, Borchelt DR. Subcellular localization of Matrin 3 containing mutations associated with ALS and distal myopathy. PLoS One. 10:e0142144, 2015. PMID:26528920. PMC:4631352
- Xu G, Stevens Jr SM, Morre BD, McClung S, Borchelt DR. Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-type amyloidosis. Hum Mol Genet, 22:2765-74. 2013. PMID:23512986. PMC3690965.