Emily Baechler Gillespie, Ph.D., Institute of Human Genetics at the University of Minnesota

Assistant Professor
Dept. of Medicine
Office: 5-144 MCB
Phone: (612) 625-4714
Fax: (612) 625-2199
e-mail: baec0005@umn.edu

RESEARCH INTERESTS

The major focus of Dr. Gillespie’s laboratory is the use of genomic and proteomic techniques for identification and validation of biomarkers for human autoimmune disease.  Currently there are three major projects based on a large biorepository of blood and urine samples from patients with systemic lupus erythematosus (SLE).  The first project seeks to identify gene expression biomarkers of SLE disease activity using blood cell RNA from longitudinally-collected samples.  In a second study, a parallel approach is being used to identify serum protein biomarkers of SLE activity.  In both of these studies, we hope to identify biomarkers that reflect current disease activity, as well as those that precede disease flare.  The results of these studies will increase our understanding of the pathogenic mechanisms underlying disease flare and may be useful in the clinical monitoring of patients with SLE.

A third project focuses on the genetic determinants of blood cell gene expression in SLE.  A number of interesting gene expression signatures have already been identified in SLE patients, including a signature that reflects activation of the type I interferon pathway.  However, it is has not been shown whether these signatures are causative for disease or are instead effects of the disease process.  We are generating both whole genome gene expression data (microarray) and genotype data (500K SNP chips) on 300 SLE patients.  The goal is to identify genetic determinants of SLE gene expression signatures.  This study may reveal biological pathways that lead to SLE, and would thus identify new targets for therapy.  The results will also help us prioritize candidate genes in the era of genome-wide association studies. 

Selected Recent Publications

• Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, Ytterberg  S, Gregersen PK, Behrens TW, Reed AM.  2007. An interferon signature in peripheral blood cells is associated with disease activity in patients with dermatomyositis. Molecular Medicine 13(1-2):59-68. 
• Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC, Plenge RM, Koeuth T, Ortmann WA, Hom G, Bauer JW, Gillett C, Burtt N, Cunninghame Graham DS, Onofrio R, Petri M, Gunnarsson I, Svenungsson E, Ronnblom L, Nordmark G, Gregersen PK, Moser K, Gaffney PM, Criswell LA, Vyse TJ, Syvanen AC, Bohjanen PR, Daly MJ, Behrens TW, Altshuler D. 2007. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci USA 104(16):6758-63.
• Graham RR*, Kozyrev SV*, Baechler EC*, Reddy MV*, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Escribano MF, the Argentine Collaborative group, Pons-Estel B, Petri M, Gregersen PK, Daly M, Altshuler D, Martín J, Behrens TW, Alarcón-Riquelme ME. 2006. A common haplotype of interferon regulatory factor 5 (IRF-5) regulates mRNA splicing and expression, and is associated with increased genetic risk in human SLE. Nat Genet 38(5):550-55.
• Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Moser KL, Ortmann WA, Espe KJ, Balasubramanian S, Hughes KM, Chan JP, Begovich A, Chang SP, Gregersen PK, Behrens TW.  2004. Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation.  Genes Immun 5(5):347-53.
• Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW. 2003. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 100:2610-5.