Epigenetics refers to heritable changes in gene expression and/or phenotype without mutations in DNA sequences. Histone modifications including methylation, acetylation and phosphorylation as well as modifications on DNA such as DNA methylation and hydroxymethylation are epigenetic marks. These epigenetic marks are critical to regulate gene expression. Changes in histone modifications have also been observed in the Epidemiology of Diabetic Interventions and Complications (EDIC) study and is proposed to confer ?memory? of hyperglycemia. However, it is largely unexplored on how epigenetic alterations contribute to the development of diabetic gastroparesis. In this program project grants, all three projects will analyze epigenetic changes during diabetic development using mouse models and human patient samples using epigenomic methods including ChIP-seq. ChIP-seq and MeDIP-seq are state of art techniques to analyze histone modifications and DNA methylation, respectively, on a genome-wide scale. While these approaches may be considered standard practice for highly focused epigenomic laboratories, they are not for most laboratories and institutions including the 3 Project laboratories. The Epigenomic and Transcriptomic Core (Core B) will have designated scientists to provide expertise supporting each program project, will establish a set of common protocols and procedures for acquisition of reliable and comparable epigenomic and transcriptomic data, and provide tertiary bioinformatics support to analyze the epigenome and transcriptome to gain insight into the impact of epigenetic changes on diabetic gastroparesis. The work of this Core will support the needs of each Project, help obtain reliable datasets, facilitate the successful completion of each program project and reduce cost.

Public Health Relevance

The Epigenomic and Transcriptomic Core (Core B) will have designated scientists to provide expertise supporting each program project, will establish a set of common protocols and procedures for acquisition of reliable and comparable epigenomic and transcriptomic data, and provide tertiary bioinformatics analysis of the epigenome and transcriptome datasets to gain insight into the impact of epigenetic changes on diabetic gastroparesis

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK068055-13
Application #
9315829
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
13
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Cipriani, Gianluca; Gibbons, Simon J; Miller, Katie E et al. (2018) Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice. Gastroenterology 154:2122-2136.e12
Desai, A; O'Connor, M; Neja, B et al. (2018) Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms. Neurogastroenterol Motil 30:e13365
Miller, K E; Bajzer, Ž; Hein, S S et al. (2018) High temporal resolution gastric emptying breath tests in mice. Neurogastroenterol Motil :e13333
Karakashev, Sergey; Zhu, Hengrui; Wu, Shuai et al. (2018) CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity. Nat Commun 9:631
Rajan, Elizabeth; Al-Bawardy, Badr; Gostout, Christopher J et al. (2018) Endoscopic muscle biopsy sampling of the duodenum and rectum: a pilot survival study in a porcine model to detect myenteric neurons. Gastrointest Endosc 87:600-606
Zhong, Jian; Ye, Zhenqing; Lenz, Samuel W et al. (2017) Purification of nanogram-range immunoprecipitated DNA in ChIP-seq application. BMC Genomics 18:985
Parthasarathy, Gopanandan; Kudva, Yogish C; Low, Phillip A et al. (2017) Relationship Between Gastric Emptying and Diurnal Glycemic Control in Type 1 Diabetes Mellitus: A Randomized Trial. J Clin Endocrinol Metab 102:398-406
Gibbons, Simon J; Grover, Madhusudan; Choi, Kyoung Moo et al. (2017) Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis. PLoS One 12:e0187772
Hayashi, Yujiro; Toyomasu, Yoshitaka; Saravanaperumal, Siva Arumugam et al. (2017) Hyperglycemia Increases Interstitial Cells of Cajal via MAPK1 and MAPK3 Signaling to ETV1 and KIT, Leading to Rapid Gastric Emptying. Gastroenterology 153:521-535.e20
Camilleri, Michael; McCallum, Richard W; Tack, Jan et al. (2017) Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study. Gastroenterology 153:1240-1250.e2

Showing the most recent 10 out of 134 publications