Dr. Sergey Pyrkhozhij

Biography

Dr. Sergey Prykhozhij is a Research Associate and Scientific Lead in the lab of Dr. Jason Berman at Children’s Hospital of Eastern Ontario (CHEO) Research Institute. He moved to this position from Dalhousie University in October 2019 to continue research on cancer-related and rare genetic disease modeling in zebrafish. He is a molecular biologist with a developmental biological training and mindset. Dr. Prykhozhij obtained his PhD from Heidelberg University for work done at the European Molecular Biology Laboratory (EMBL). His thesis work was on the role of Sonic Hedgehog in zebrafish fin bud proliferation and its connection with p53 in regulating survival, cell-cycle exit and differentiation in zebrafish central nervous system and retina. His first one-year postdoctoral position at EMBL was on characterising the response of microglia and macrophages to increased apoptosis in the zebrafish brain. His second post-doctoral position was on the mechanisms of tissue-specific gene regulation by the Glucocorticoid Receptor (GR) in zebrafish at the Bioinformatics department of MPI-MG. After this training, he moved to Canada in 2012 and has since worked in disease modeling and gene editing technology development in zebrafish.

Gene editing technology development in zebrafish

An important focus of Dr. Prykhozhij’s work remains optimization and development of gene editing tools such as CRISPR/Cas9 and prime editing especially in the context of inserting precise amino acid substitutions. He has contributed significantly to this area of zebrafish disease modeling by developing computational and experimental tools as well as by writing review articles on the subject.

Cancer disease modeling in zebrafish

Since his PhD, Dr. Prykhozhij has been fascinated by the function of p53 in both developmental disorders and cancer. As part of the Berman lab team, Dr. Prykhozhij established a line of research on modeling of the Li-Fraumeni Syndrome resulting from germline mutations in TP53. This work is currently being published in high-profile journals, and new zebrafish models are being developed to investigate the human p53 protein mutants directly. As part of this project, Dr. Prykhozhij is working on developing new tools to understand molecular activities of both wild-type and mutant p53 proteins and supervising work by graduate students involved in the project.

Rare disease modeling

Dr. Prykhozhij has been involved in a variety of disease modeling projects in zebrafish. The major focus of this work has been related to hematopoietic and inflammatory disorders. Several projects were related to retinal vasculature as part of collaborations with human geneticists at the IWK Health Centre. Another major project was on muscular dystrophy disease models. This work is very helpful in translating the human genetics findings to better biological understanding of the pathogenesis and potential treatments. The most recent project in this area was on Fe-S protein biogenesis, where members of the Berman lab were part of a large international collaboration. Dr. Prykhozhij is currently working on characterizing and investigating several blood-related disorders, a tRNA-related disease model and a vasculature-related disorder.

Selected publications

• Prykhozhij SV, Kevin Ban, Zane L. Brown, Kim Kobar, Gabriel Wajnberg, Charlotte Fuller, Simi Chacko, Jacynthe Lacroix, Nicolas Crapoulet, Craig Midgen, Adam Shlien, David Malkin and Jason N. Berman. miR-34a has direct and p53-linked effects on tumor suppression, metabolism, and regulation of hematopoiesis. PLOS Genetics, in revision.
   
• Clara D.M. van Karnebeek, Maja Tarailo-Graovac, René Leen, Rutger Meinsma, Solenne Correard, Judith Jansen-Meijer, Sergey V. Prykhozhij, Izabella A Pena, Kevin Ban, Sarah Schock, Vishal Saxena, Mia L. Pras-Raves, Britt I. Drögemöller, Anita E. Grootemaat, Nicole N. van der Wel, Doreen Dobritzsch, Winfried Roseboom, Bauke V. Schomakers, Yorrick R.J. Jaspers, Lida Zoetekouw, Jeroen Roelofsen, Carlos R. Ferreira1, Robin van der Lee, Colin J. Ross, Jakub Kochan, Rebecca L. McIntyre, Jan B. van Klinken, Michel van Weeghe, Gertjan Kramer, Bernhard Weschke, Philippe Labrune, Michèl A. Willemsen, Daria Riva, Barbara Garavaglia, John B. Moeschler, James J. Filiano, Marc Ekker, Jason N. Berman, David Dyment, Frédéric M. Vaz, Wyeth W. Wassermann, Riekelt H. Houtkooper and André B.P. van Kuilenburg. CIAO1 and MMS19 deficiency: a lethal neurodegeneration phenotype caused by cytosolic Fe-S cluster protein assembly disorders. Genetics in Medicine, accepted.
   
• Prykhozhij SV, Berman JN. Mutation Knock-in Methods Using Single-Stranded DNA and Gene Editing Tools in Zebrafish. Methods Mol Biol. 2024;2707:279-303. doi: 10.1007/978-1-0716-3401-1_19.
   
• Prykhozhij SV, Caceres L, Ban K, Cordeiro-Santanach A, Nagaraju K, Hoffman EP, Berman JN. Loss of calpain3b in Zebrafish, a Model of Limb-Girdle Muscular Dystrophy, Increases Susceptibility to Muscle Defects Due to Elevated Muscle Activity. Genes (Basel). 2023 Feb 15;14(2):492.
   
• Biggs CM, Cordeiro-Santanach A, Prykhozhij SV, Deveau AP, Lin Y, Del Bel KL, Orben F, Ragotte RJ, Saferali A, Mostafavi S, Dinh L, Dai D, Weinacht KG, Dobbs K, Ott de Bruin L, Sharma M, Tsai K, Priatel JJ, Schreiber RA, Rozmus J, Hosking MC, Shopsowitz KE, McKinnon ML, Vercauteren S, Seear M, Notarangelo LD, Lynn FC, Berman JN, Turvey SE.           Human JAK1 gain of function causes dysregulated myelopoeisis and severe allergic inflammation. JCI Insight. 2022 Dec 22;7(24):e150849.
   
• Ketharnathan S, Rajan V, Prykhozhij SV, Berman JN. Zebrafish models of inflammation in hematopoietic development and disease. Front Cell Dev Biol. 2022 Jul 18; 10:955658.
   
• Rajan V, Prykhozhij SV, Pandey A, Cohen AM, Rainey JK, Berman JN. KIT D816V is dimerization-independent and activates downstream pathways frequently perturbed in mastocytosis. Br J Haematol. 2022 Mar 4.
   
• Rajan V, Collett K, Woodside R, Prykhozhij SV, Moksa M, Carles A, Wong M, Liebman M, Hirst M, Berman JN. Stress hematopoiesis induces a proliferative advantage in TET2 deficiency. Leukemia. 2022 Mar;36(3):809-820.
   
• Prykhozhij SV, Rajan V, Ban K, Berman JN. CRISPR Knock-in Designer: Automatic Oligonucleotide Design Software to Introduce Point Mutations by Gene Editing Methods.  Re: GEN Open 1 (1), 53-67. 
   
• Kobar K, Collett K, Prykhozhij SV, Berman JN. Zebrafish Cancer Predisposition Models. Front Cell Dev Biol. 2021 Apr 27;9:660069.
   
• Prykhozhij SV, Cordeiro-Santanach A, Caceres L, Berman JN. Genome Editing in Zebrafish Using High-Fidelity Cas9 Nucleases: Choosing the Right Nuclease for the Task. Methods Mol Biol. 2020;2115:385-405.
   
• Caceres L, Prykhozhij SV, Cairns E, Gjerde H, Duff NM, Collett K, Ngo M, Nasrallah GK, McMaster CR, Litvak M, Robitaille JM, Berman JN. Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina. Dev Dyn. 2019 Dec;248(12):1243-1256.
   
• Prykhozhij SV, Berman JN. Zebrafish knock-ins swim into the mainstream. Dis Model Mech. 2018 11(10).
   
• Prykhozhij SV, Fuller C, Steele SL, Veinotte CJ, Razaghi B, Robitaille JM, McMaster CR, Shlien A, Malkin D, Berman JN. Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9. Nucleic Acids Res. 2018 46(17):9252.
   
• Prykhozhij SV, Caceres L, Berman JN. New Developments in CRISPR/Cas-based Functional Genomics and their Implications for Research using Zebrafish. Curr Gene Ther. 2017; 17(4):286-300.
   
• Prykhozhij SV, Steele SL, Razaghi B, Berman JN. A rapid and effective method for screening, sequencing and reporter verification of engineered frameshift mutations in zebrafish. Dis Model Mech. 2017; 10(6):811-822.
   
• Ceasar SA, Rajan V, Prykhozhij SV, Berman JN, Ignacimuthu S. Insert, remove or replace: A highly advanced genome editing system using CRISPR/Cas9. Biochim Biophys Acta. 2016; 1863(9):2333-44.17. 
   
• Telorac J, Prykhozhij SV, Schöne S, Meierhofer D, Sauer S, Thomas-Chollier M, Meijsing SH. Identification and characterization of DNA sequences that prevent glucocorticoid receptor binding to nearby response elements. Nucleic Acids Res. 2016; 44(13):6142-56.
   
• Prykhozhij SV, Rajan V, Berman JN. A Guide to Computational Tools and Design Strategies for Genome Editing Experiments in Zebrafish Using CRISPR/Cas9. Zebrafish. 2016; 13(1):70-3.
   
• Fernández-Murray JP, Prykhozhij SV, Dufay JN, Steele SL, Gaston D, Nasrallah GK, Coombs AJ, Liwski RS, Fernandez CV, Berman JN, McMaster CR. Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. PLoS Genet. 2016; 12(1):e1005783.
   
• Prykhozhij SV, Rajan V, Gaston D, Berman JN. CRISPR multitargeter: a web tool to find common and unique CRISPR single guide RNA targets in a set of similar sequences. PLoS One. 2015; 10(3):e0119372.
   
• Steele SL, Prykhozhij SV, Berman JN. Zebrafish as a model system for mitochondrial biology and diseases. Transl Res. 2014; 163(2):79-98.
   
•  Prykhozhij SV, Marsico A, Meijsing SH. Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets. Zebrafish. 2013; 10(3):303-15.
   
• Prykhozhij SV. In the absence of Sonic hedgehog, p53 induces apoptosis and inhibits retinal cell proliferation, cell-cycle exit and differentiation in zebrafish. PLoS One. 2010; 5(10):e13549.
   
• Prykhozhij SV, Neumann CJ. Distinct roles of Shh and Fgf signaling in regulating cell proliferation during zebrafish pectoral fin development. BMC Dev Biol. 2008; 8:91.