? The candidate has been previously studying the mechanisms of insulin-regulated glucose transport in 3T3-L1 adipocytes using RNAi technology and later focused on the mechanisms of RNAi and profiling of microRNAs in cancer cells and mouse tissues. To continue her training in the field of diabetes, she has recently joined Dr. Sabire Ozcan's laboratory. Dr. Ozcan's research focuses mainly on glucose-regulated insulin gene transcription in pancreatic beta-cells. The immediate career goal of the candidate is to better acquaint herself with experimental procedures and applications in the regulation of insulin gene expression and glucose regulation of pancreatic beta-cell function. This training will allow her to pursue her long-term goal, which is to study the role of miRNAs in regulating beta-cell function and to elucidate the role of miRNAs in the development of type-ll diabetes, as an independent investigator. ? Recent studies indicate that a novel population of cellular small RNAs, termed microRNAs (miRNAs), may play an important role in the development of type 2 diabetes. The expression of these miRNAs may be highly regulated under various environmental and physiological conditions; dysregulation of these small RNAs may lead to the development of type 2 diabetes. For example, miR-375 has been discovered to be specifically expressed in pancreatic beta cells and be important in insulin secretion. The functions of most miRNAs in beta cells await to be investigated. The hypothesis of the P.I. is that miRNAs are not functioning alone, but rather, multiple miRNAs act in cohort to regulate beta cell development and insulin production and secretion in response to glucose.
The specific aims of this project are: (1) To profile miRNA expression in pancreatic beta cells, in order to identify novel cell-specific and glucose-regulated miRNAs with a recently developed rational miRNA microarray technology; (2) To study the function of the identified glucose-regulated and beta cell-specific miRNAs in MIN6 cells by transfecting with synthetic miRNAs to study overexpression effects and with 2-O-methyl RNA antagomirs to investigate the effects associated with their down-regulation. The results obtained from the proposed activities may lead to the discovery of novel miRNAs or new roles of miRNA network in the development of type 2 diabetes and potential therapeutic approaches to treat or prevent this disease. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01DK078648-01
Application #
7299166
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2007-09-10
Project End
2010-08-31
Budget Start
2007-09-10
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$99,335
Indirect Cost
Name
University of Kentucky
Department
Biochemistry
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Teotia, Sachin; Singh, Deepali; Tang, Xiaoqing et al. (2016) Essential RNA-Based Technologies and Their Applications in Plant Functional Genomics. Trends Biotechnol 34:106-123
Shi, Lina; Tang, Xiaoqing; Tang, Guiliang (2016) GUIDE-Seq to Detect Genome-wide Double-Stranded Breaks in Plants. Trends Plant Sci 21:815-818
Tang, Guiliang; Tang, Xiaoqing (2013) Short tandem target mimic: a long journey to the engineered molecular landmine for selective destruction/blockage of microRNAs in plants and animals. J Genet Genomics 40:291-6
Mao, Yiping; Mohan, Ramkumar; Zhang, Shungang et al. (2013) MicroRNAs as pharmacological targets in diabetes. Pharmacol Res 75:37-47
Zhao, Xiaomin; Mohan, Ramkumar; Özcan, Sabire et al. (2012) MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic ?-cells. J Biol Chem 287:31155-64
Tang, Guiliang; Yan, Jun; Gu, Yiyou et al. (2012) Construction of short tandem target mimic (STTM) to block the functions of plant and animal microRNAs. Methods 58:118-25
Yan, Jun; Gu, Yiyou; Jia, Xiaoyun et al. (2012) Effective small RNA destruction by the expression of a short tandem target mimic in Arabidopsis. Plant Cell 24:415-27
Tang, Xiaoqing; Tang, Xiaohu; Gal, Jozsef et al. (2011) Detection of microRNAs in prostate cancer cells by microRNA array. Methods Mol Biol 732:69-88
Tang, Xiaoqing; Muniappan, Latha; Tang, Guiliang et al. (2009) Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA 15:287-93
Tang, Xiaoqing; Tang, Guiliang; Ozcan, Sabire (2008) Role of microRNAs in diabetes. Biochim Biophys Acta 1779:697-701