This Histopathology Core B will be housed at University of Chicago. Core B will be responsible for the histopathological analysis of muscle tissue. The hallmark pathological features of muscular dystrophy include: variation in fiber size, central nucleation, increased extracellular matrix deposition, fatty infiltration, immune cell infiltration, apoptosis, necrosis, calcification and regeneration. Each of these features can be measured either by histopathological examination or by assays that can be performed on an entire muscle. A cardinal feature of the muscular dystrophies is that the pathological findings are not uniformly distributed across a muscle group. To circumvent sampling error that can complicate histopathological analysis, this Core has established quantitative assays that can be used to reflect the process across the entire muscle that is being assayed. This core will provide histopathological examination of the animals generated in the Projects. Quantitative assays across muscle groups will also be performed. Each project will use Core B. The Core's function and output will be overseen by an experienced neuropathologist who has a special interest in muscular dystrophy. The Core will be housed in the Histopathology Core Facility within the Molecular Cardiology/Institute for Cardiovascular Research at the University of Chicago. This facility, established in the early 1990's, has had benefit of stable technical direction and oversight. With the increase in samples to be processed from each of the three Projects in this program, the technical director will supervise the training of new technical staff who will then be responsible for the processing of samples related to the Program.

Public Health Relevance

In muscular dystrophy, the muscle appears abnormal and displays increased fibrosis, cell disruption, regeneration and other features. These features will be uniformly assessed by this Core facility to ensure that comparisons can be made from multiple experiments. Consistent and even measurements of muscle pathology are a necessary component for each of the Projects in this Program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS072027-04
Application #
8685349
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60637
Quattrocelli, Mattia; McNally, Elizabeth M (2016) BMP and WNT: the road to cardiomyocytes is paved with precise modulation. Stem Cell Investig 3:21
Lamar, Kay-Marie; Bogdanovich, Sasha; Gardner, Brandon B et al. (2016) Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ. PLoS Genet 12:e1006019
McNally, Elizabeth M (2016) Questions and Answers About Myostatin, GDF11, and the Aging Heart. Circ Res 118:6-8
Tjondrokoesoemo, Andoria; Schips, Tobias; Kanisicak, Onur et al. (2016) Genetic overexpression of Serpina3n attenuates muscular dystrophy in mice. Hum Mol Genet 25:1192-202
Lamar, Kay-Marie; Miller, Tamari; Dellefave-Castillo, Lisa et al. (2016) Genotype-Specific Interaction of Latent TGFβ Binding Protein 4 with TGFβ. PLoS One 11:e0150358
Demonbreun, Alexis R; Allen, Madison V; Warner, James L et al. (2016) Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption. Am J Pathol 186:1610-22
Demonbreun, Alexis R; McNally, Elizabeth M (2016) Plasma Membrane Repair in Health and Disease. Curr Top Membr 77:67-96
Tjondrokoesoemo, Andoria; Schips, Tobias G; Sargent, Michelle A et al. (2016) Cathepsin S Contributes to the Pathogenesis of Muscular Dystrophy in Mice. J Biol Chem 291:9920-8
Gardner, Brandon B; Swaggart, Kayleigh A; Kim, Gene et al. (2015) Cardiac function in muscular dystrophy associates with abdominal muscle pathology. J Neuromuscul Dis 2:39-49
Burr, A R; Molkentin, J D (2015) Genetic evidence in the mouse solidifies the calcium hypothesis of myofiber death in muscular dystrophy. Cell Death Differ 22:1402-12

Showing the most recent 10 out of 60 publications