Zhenya Ivakine

Interrogation of gene editing and genome engineering technologies to elucidate disease pathogenesis and develop therapeutic strategies for rare inherited disorders. Development of functional genomics approaches to understand consequences of coding variants in disease-causing genes. Generation and characterization of humanized animal models of genetic disease.

Research Synopsis

Research Interests: Interrogation of gene editing and genome engineering technologies to elucidate disease pathogenesis and develop therapeutic strategies for rare inherited disorders. Development of functional genomics approaches to understand consequences of coding variants in disease-causing genes. Generation and characterization of humanized animal models of genetic disease.

Keywords: Muscular Dystrophy, Niemann Pick Disease type C, Cystic Fibrosis, cell and animal models, gene therapy and genome editing, CRISPR/Cas systems, disease modifiers, next generation sequencing, saturational mutagenesis.

Detailed Description:
The current focus of my research program is utilization of genome engineering technologies, including development of novel delivery strategies, to understand disease pathogenesis and as therapeutic tools for the treatment of several genetic disorders. These have included Niemann Pick Type 1C (NPC), Cystic Fibrosis, MECP2 duplication syndrome, and Duchenne Muscular Dystrophy (DMD). In addition, we are developing saturational mutagenesis approaches to characterize and assign clinical significance to all possible variants of the NPC1 gene at a single nucleotide resolution.

Collaborators: Drs. Ronald Cohn, Anthony Gramolini, Christine Bear, Michael Salter, Paul Santerre, Michael Wilson.

METHODS USED

Cell and tissue culture: fibroblasts, myoblasts, iPSCs.

Procedures: Gene editing and genome engineering, generation and characterization of humanized animal models of a disease, transcriptional and epigenetic control of disease modifiers, next generation sequencing, AAV vectors, proteomics, cell and molecular biology, behavioral analysis.

EQUIPMENT USED

Culture hood, culture incubators, BioRad documentation system, low- and high-speed centrifuges, PCR and real-time PCR instruments, QIAcube for automated DNA and RNA extraction, confocal microscope, QIAxcel advanced system for electrophoresis, SeqStudio Genetic Analyzer for in house sequencing.

Recent Publications

Erwood S., Laselva O., Bily T.M.I., Brewer R.A., Rutherford A.H., Bear C.E., Ivakine E.A.* * - senior corresponding author. (2020). Allele specific prevention of nonsense mediated decay in cystic fibrosis using homology-independent genome editing. Molecular Therapy -Methods and Clinical Development. (in press)

Erwood S , Brewer RA , Bily TMI , Maino E , Zhou L , Cohn RD , Ivakine EA* *-senior corresponding author. (2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation. Genome research. 29(12): 2010-2019.

Kemaladewi DU , Bassi PS , Erwood S , Al-Basha D , Gawlik KI , Lindsay K , Hyatt E , Kember R , Place KM , Marks RM , Durbeej M , Prescott SA , Ivakine EA* , Cohn RD* *) Co-senior authors. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. Nature. 572(7767): 125-130.

Kemaladewi DU , Maino E , Hyatt E , Hou H , Ding M , Place KM , Zhu X , Bassi P , Baghestani Z , Deshwar AG , Merico D , Xiong HY , Frey BJ , Wilson MD , Ivakine EA* , Cohn RD*. *) Co-senior authors. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed repair-independent mechanism. Nature medicine. 23(8): 984-989.

Full bibliography: https://www.ncbi.nlm.nih.gov/myncbi/evgueni.ivakine.1/bibliography/public/

Appointments

Primary: Physiology
Scientist, Hospital for Sick Children
Program in Genetics and Genome Biology