Assistant Professor of Medicine
752 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: 215-573-6639
Fax: 215-573-7599
Email : kiriakim@uphs.upenn.edu
Research Interests
microRNAs, Argonaute, microRNP, microRNA-mediated gene regulation, RNAi, non coding RNAs.
Animal models of Systemic Lupus Erythematosus, microRNAs in Systemic Lupus Erythematosus, microRNA therapeutics.
Research Programs
Animal microRNAs and Argonaute
RNA interference (RNAi) operates as a mechanism of innate immunity in plants, drosophila and C. elegans and depends on double stranded RNA and proteins of the Argonaute family. RNAi, programmed by exogenous small interfering RNAs (siRNA), is a powerful tool for gene-specific studies. The function of endogenous mammalian siRNAs, expressed primarily in oocytes, remains elusive.
The microRNA pathway intersects with the RNAi pathway and regulates gene expression in plants and animals. Mammalian microRNAs bind directly to Argonaute proteins (Ago1-4), providing target specificity to the regulatory function of Ago complexes. The mechanisms by which Agos regulate gene expression in mammals are not completely understood. Research in our lab focuses on the biology of Ago proteins. We are studying the expression, regulation and function of Agos using human and mouse cell lines and primary cells, mouse models and in vitro systems.
microRNAs in Systemic Lupus Erythematosus
microRNAs are involved in numerous biological processes and their expression is differentially regulated in human disease. Systemic Lupus Erythematosus (SLE, lupus) is a prototype systemic autoimmune disease characterized by autoantibody production and tissue deposition of immune complexes. The SLE immunopathology is characterized by aberrant B and T cell functions and interactions.
We are studying the role of microRNAs in pathways contributing to characteristic B and T cell phenotypes and organ damage in SLE using microRNA KO models and mouse lupus models (congenic and induced). We also use synthetic inhibitors for microRNA silencing in vivo, to complement our genetic studies and to investigate potential use of microRNA inhibitors in SLE therapeutics.
Recent Peer Reviewed Publications
1. Tan GS, Chiu CH, Garchow BG, Metzler D, Diamond SL, Kiriakidou M. Small Molecule Inhibition of RISC Loading. ACS Chem Biol. 2011 Nov 11. [Epub ahead of print]
2. Garchow BG, Encinas OB, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, Obad S, Petri A, Kauppinen S, Kiriakidou M. Silencing of microR6-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med. 3(10), 605-15. Epub 2011 Sep 1.
3. Tan GS, Garchow BG, Liu X, Metzler D, Kiriakidou M. Clarifying mammalian RISC assembly in vitro. BMC Mol Biol. 12:19, 2011.
4. Tan G. S, Garchow B.G. Liu X, Yeung J, Morris J P, Cuellar T, McManus MT and M Kiriakidou. : Expanded RNA-binding activities of mammalian Ago2. Nucleic Acids Res. 37(22): 7533-45, 2009.
5. 14. Kiriakidou M, Tan GS, Lamprinaki S, De Plannell-Saguer M, Nelson PT and Mourelatos Z. : An mRNA m7G cap binding-like motif within human Argonaute2 represses translation. Cell 129(6): 1141-51, 2007. Epub 2007 May 24.
Kiriakidou Lab:
742 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6160
Phone: 215-573-0677
Lab Personnel:
Barry Garchow, Ph.D.
Grace Tan, Ph.D.
