The dual goals of this proposal are to investigate the function of microRNAs in hematopoietic/T cell development and to establish the applicant as an independent investigator. MicroRNAs represent a novel class of small regulatory RNAs. miRNAs control gene expression by base pairing with miRNA-recognition elements found in their mRNA targets. The effects of miRNAs in gene expression regulation are pleiotropic, miRNAs control cellular proliferation, apoptosis and development, although many of the genes that mammalian miRNAs regulate are unknown. The role of miRNAs in T lymphocytes and their development is completely unknown. Studies to address the function of miRNAs in hematopoietic/T cell development promise to unravel novel pathways that control hematopoietic/lymphocytic development and at the same time enhance our understanding of the function of miRNAs.
In Aim #1, mRNA targets for mammalian miRNAs will be identified. An experimental-computational approach is presented along with strategies for validation of miRNA targets.
In Aim #2, the function of miRNAs in murine hematopoietic/T cell development will be investigated. The applicant has spent the last several years for a career as a physician-scientist, through her prior research training in the molecular biology of steroidogenesis and clinical training in Internal Medicine and Rheumatology. Drs. Warren Pear, Zissimos Mourelatos and Philip Cohen, recognized for their expertise in the fields of T cell development and Immunology (Drs. Pear and Cohen) and microRNA biology (Dr. Mourelatos), will sponsor the candidate's scientific development. The quality of the research facilities and the diversity of the resources available at the Sponsoring Institution in combination with the intellectual and academic strength of the sponsors, provide an ideal setting for the conduction of the proposed studies. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI063030-03
Application #
7228418
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2005-05-15
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$114,501
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Garchow, Barry G; Bartulos Encinas, Oscar; Leung, Yiu Tak et al. (2011) Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med 3:605-15
Tan, Grace S; Garchow, Barry G; Liu, Xuhang et al. (2011) Clarifying mammalian RISC assembly in vitro. BMC Mol Biol 12:19
Nelson, Peter T; De Planell-Saguer, Mariangels; Lamprinaki, Stella et al. (2007) A novel monoclonal antibody against human Argonaute proteins reveals unexpected characteristics of miRNAs in human blood cells. RNA 13:1787-92
Kiriakidou, Marianthi; Tan, Grace S; Lamprinaki, Styliani et al. (2007) An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129:1141-51