Voula Kanelis

faculty_img Academic Title: Associate Professor

Campus: UTM

CSB Appointment: Cross Appointment

Primary Undergraduate Department:
Chemistry, UTM

Graduate Programs:
Cell & Systems Biology

Titles and Honors:
CIHR New Investigator (2012)

Academic or Administrative Appointments:
Education:
Ph.D. University of Toronto 2001
B.Sc. University of Western Ontario 1995

 

Mailing Address
Department of Cell & Systems Biology
University of Toronto
3359 Mississauga Road North
Mississauga, ON L5L 1C6
Canada

 

Contact Information
Office phone: 905-569-4542
Office: DV 4042
Lab:
Lab phone:
Email: voula.kanelis@utoronto.ca
URL: sites.google.com/site/kanelislaboratory/

 

Research Areas
Structural Biology

 

Research

Research in the laboratory is focused on two main areas: ABC transporters and phage proteins. We use a combination of NMR spectroscopy and other biophysical tools to obtain information about the structure, interactions, and dynamics of proteins.
ABC transporters are multi-domain, integral membrane proteins found in all species and consist of two repeats each comprised of a membrane spanning domain (MSD) and a cytoplasmic nucleotide binding domain (NBD). ATP binding and hydrolysis at the NBDs results in transport of solutes across biological membranes. ABC proteins are of vast biomedical importance. ABC protein-mediated pumping of cytotoxic molecules from cells confers multidrug resistance to bacterial and tumour cells. Furthermore, many genetic diseases are caused by mutations of specific ABC proteins. We are studying two different ABC proteins in the lab: (1) Ycf1p, a Cd transporter in yeast; (2) sulfonylurea receptors (SUR), which form regulatory subunits in K+ channels. Studies of Ycf1p are aimed at understanding the basic mechanisms of regulation of ABC transporters. Studies of SUR proteins are aimed at understanding the molecular defects caused by disease-causing mutations in the proteins and how we can correct these defects with drugs.
Our work on phage proteins is focused on an HNH endonuclease a the lambda-like bacteriophage. The HNH protein is critical for the phage replication cycle. We are performing structural studies of the protein to understand the molecular basis for its function in phage morphogenesis. This work will ultimately lead to generation of designer phages that can be used to treat antibiotic resistant bacteria.

 

Publications


2017

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Molecular basis for the binding and modulation of V-ATPase by a bacterial effector protein. Zhao J, Beyrakhova K, Liu Y, Alvarez CP, Bueler SA, Xu L, Xu C, Boniecki MT, Kanelis V, Luo ZQ, Cygler M, Rubinstein JL. PLoS Pathog. 2017 Jun 1;13(6):e1006394. doi: 10.1371/journal.ppat.1006394. eCollection 2017 Jun.
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Hyperinsulinism-Causing Mutations Cause Multiple Molecular Defects in SUR1 NBD1. Alvarez CP, Stagljar M, Muhandiram DR, Kanelis V. Biochemistry. 2017 May 9;56(18):2400-2416. doi: 10.1021/acs.biochem.6b00681. Epub 2017 Apr 25.
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From ions to insulin. Kanelis V. Elife. 2017 Mar 9;6. pii: e25159. doi: 10.7554/eLife.25159.
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2015

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Phosphorylation-dependent changes in nucleotide binding, conformation, and dynamics of the first nucleotide binding domain. de Araujo ED, Alvarez CP, López-Alonso JP, Sooklal CR, Stagljar M, Kanelis V. J Biol Chem. 2015 Sep 11;290(37):22699-714. doi: 10.1074/jbc.M114.636233. Epub 2015 Jul 21.
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2014

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Successful development and use of a thermodynamic stability screen for optimizing the yield of nucleotide binding domains.de Araujo ED, Kanelis V.Protein Expr. Purif. 2014 Nov;103:38-47
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HNH proteins are a widespread component of phage DNA packaging machines.Kala S, Cumby N, Sadowski PD, Hyder BZ, Kanelis V, Davidson AR, Maxwell KL.Proc. Natl. Acad. Sci. U.S.A. 2014 Apr;111(16):6022-7
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2012

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NMR and fluorescence studies of drug binding to the first nucleotide binding domain of SUR2A.López-Alonso JP, de Araujo ED, Kanelis V.Biochemistry 2012 Nov;51(45):9211-22
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The protein gp74 from the bacteriophage HK97 functions as a HNH endonuclease.Moodley S, Maxwell KL, Kanelis V.Protein Sci. 2012 Jun;21(6):809-18
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2011

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The first nucleotide binding domain of the sulfonylurea receptor 2A contains regulatory elements and is folded and functions as an independent module.de Araujo ED, Ikeda LK, Tzvetkova S, Kanelis V.Biochemistry 2011 Aug;50(31):6655-66
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NMR spectroscopy to study the dynamics and interactions of CFTR.Kanelis V, Chong PA, Forman-Kay JD.Methods Mol. Biol. 2011;741:377-403
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2010

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The solution structure of the C-terminal Ig-like domain of the bacteriophage λ tail tube protein.Pell LG, Gasmi-Seabrook GM, Morais M, Neudecker P, Kanelis V, Bona D, Donaldson LW, Edwards AM, Howell PL, Davidson AR, Maxwell KL.J. Mol. Biol. 2010 Oct;403(3):468-79
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NMR evidence for differential phosphorylation-dependent interactions in WT and DeltaF508 CFTR.Kanelis V, Hudson RP, Thibodeau PH, Thomas PJ, Forman-Kay JD.EMBO J. 2010 Jan;29(1):263-77
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2009

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The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system.Pell LG, Kanelis V, Donaldson LW, Howell PL, Davidson AR.Proc. Natl. Acad. Sci. U.S.A. 2009 Mar;106(11):4160-5
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2008

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Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain.Bruce MC, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D.Biochem. J. 2008 Oct;415(1):155-63
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2007

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CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices.Baker JM, Hudson RP, Kanelis V, Choy WY, Thibodeau PH, Thomas PJ, Forman-Kay JD.Nat. Struct. Mol. Biol. 2007 Aug;14(8):738-45
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Nuclear magnetic resonance (NMR) solution structure, dynamics, and binding properties of the kringle IV type 8 module of apolipoprotein(a).Chitayat S, Kanelis V, Koschinsky ML, Smith SP.Biochemistry 2007 Feb;46(7):1732-42
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2006

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Isotope labeling strategies for the study of high-molecular-weight proteins by solution NMR spectroscopy.Tugarinov V, Kanelis V, Kay LE.Nat Protoc 2006;1(2):749-54
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Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex.Kanelis V, Bruce MC, Skrynnikov NR, Rotin D, Forman-Kay JD.Structure 2006 Mar;14(3):543-53
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2004

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Probing slow dynamics in high molecular weight proteins by methyl-TROSY NMR spectroscopy: application to a 723-residue enzyme.Korzhnev DM, Kloiber K, Kanelis V, Tugarinov V, Kay LE.J. Am. Chem. Soc. 2004 Mar;126(12):3964-73
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2003

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Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel.Henry PC, Kanelis V, O’Brien MC, Kim B, Gautschi I, Forman-Kay J, Schild L, Rotin D.J. Biol. Chem. 2003 May;278(22):20019-28