Dr. Katherine Siminovitch — The Samuel Lunenfeld Research Institute

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Dr. Katherine Siminovitch
SENIOR INVESTIGATOR

Dr. Siminovitch has a long-standing interest in characterizing signaling pathways that regulate immune cell function. Her lab played seminal roles in defining the functions of the SHP-1 tyrosine phosphatase in autoimmune responses and the Wiskott-Aldrich syndrome protein (WASp) actin regulator in immune deficiency, and her group continues to generate new mouse models that can be used to delineate the contributions of these and other tyrosine phosphatases and cytoskeletal modulatory proteins to immune cell function.

Dr. Siminovitch is also an acclaimed leader in genomic medicine. Working with other physicians at the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Dr. Siminovitch has discovered some of the key gene variants conferring risk for rheumatoid arthritis and primary biliary cirrhosis.

By coupling her studies of human patient cohorts with the generation of unique mouse models, she is characterizing the genes that regulate normal immune responses, defining the mechanisms whereby certain proteins contribute to immune system function, and identifying the molecular pathways whereby such variants evoke cell dysfunction and disease. Dr. Siminovitch also directs a core facility that provides genotyping and sequencing services as well as guidance for design of genomics projects aimed at delineating the genetic factors modulating disease risk and outcome.

Samuel Lunenfeld
Research Institute
Mount Sinai Hospital
Joseph & Wolf Lebovic Health Complex
600 University Avenue
Toronto Ontario M5G 1X5

Tel: 416-586-4800 ext.8470
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Jul 15, 2009 04:55 PM

At a Glance

Clinician and geneticist who studies rheumatoid arthritis, primary biliary cirrhosis and Wegener’s granulomatosis
Holds the Canada Research Chair in the Mechanisms Regulating Immunologic Disease; and the Sherman Family Research Chair in Genomic Medicine
Developed a genetic test for a rare and usually fatal immune deficiency disorder called Wiskott-Aldrich Syndrome
Identified gene variants associated with risk for rheumatoid arthritis and other debilitating autoimmune diseases
Aims to provide new knowledge that will lead to “individualized” medicine

Major Research Activities

Dr. Siminovitch´s research program is directed at identifying the genetic and cellular mechanisms modulating expression of the immune response and development of immunologic diseases. The lab is now focused on defining the molecular events conferring risk for and modulating outcome of chronic autoimmune inflammatory diseases and in particular rheumatoid arthritis, primary biliary cirrhosis and Wegener’s granulomatosis. To this end, the lab capitalizes on its access to unique mouse models and patient cohorts to delineate the gene variants conferring risk for these diseases and the effector pathways linking such variants to disease.

Recent Publications

N-WASp is required for Schwann cell cytoskeletal dynamics, normal myelin gene expression and peripheral nerve myelination.

Jin F, Dong B, Georgiou J, Jiang Q, Zhang J, Bharioke A, Qiu F, Lommel S, Feltri ML, Wrabetz L, Roder JC, Eyer J, Chen X, Peterson AC, Siminovitch KA. Development. 2011 Apr;138(7):1329:37.

Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.

Hirschfield GM, Liu X, Han Y, Gorlov IP, et al. Nat Genet. 2010 Aug;42(8):655-7

Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.

Stahl EA, Raychaudhuri S, Remmers EF, et al., Nat Genet. 2010 Jun;42(6):508-14.

REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.

Gregersen PK, Amos CI, Lee AT, et al., Nat Genet. 2009 Jul;41(7):820-3.

The mDial formin is required for neutrophil polarization, migration, and activation of the LARG/RhoA/ROCK signaling axis during chemotaxis.

Shi Y, Zhang J, Mullin M, Dong B, Alberts AS, Siminovitch KA.

J Immunol. 2009 Mar 15;182(6):3837-45.

Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.

Hirschfield GM, Liu X, Xu C, Lu Y, Xie G, Lu Y, Gu X, Walker EJ, Jing K, Juran BD, Mason AL, Myers RP, Peltekian KM, Ghent CN, Coltescu C, Atkinson EJ, Heathcote EJ, Lazaridis KN, Amos CI, Siminovitch KA.

N Engl J Med. 2009 Jun 11;360(24):2544-55.

► Lunenfeld Research Repository

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