Haley Wyatt

Haley Wyatt

Assistant Professor

BSc Hons, University of Regina, 2004
PhD, University of Calgary, 2009
Postdoc, The Francis Crick Institute, 2017

Address MaRS Center, West Tower, Room 1521A
661 University Avenue
Toronto, ON M5G 1M1
Lab Wyatt Lab
Office Phone 416-978-4808
Email haley.wyatt@utoronto.ca

Haley Wyatt was born and raised in the small rural community of Broadview, Saskatchewan (Canada). Her research training in biochemistry and molecular biology began during her postgraduate studies at the Southern Alberta Cancer Research Institute and the University of Calgary. Under the supervision of Tara Beattie, she studied the human telomerase reverse transcriptase (hTERT). hTERT is the catalytic subunit of telomerase, an enzyme that has a pivotal role in cellular proliferation and organismal aging and is deregulated in many types of cancer. Haley developed the first biochemical assay to study interactions between hTERT and telomeric DNA substrates. This assay was critical for subsequent structure-function studies, in which she provided important insight into the molecular mechanisms of telomerase deficiency associated with human disease.

After receiving her PhD in 2009, Haley moved to Stephen West’s laboratory at the Francis Crick Institute (formerly Clare Hall Laboratories) in London, England to pursue her interests in DNA repair and mechanisms of genome instability. Her research has significantly advanced our understanding of the biochemical and cellular functions of the SLX4 protein and its role as a scaffold for an endonuclease DNA repair complex. This research is of particular relevance to human health because mutations in SLX4 (and its associated nucleases) are linked to Fanconi anemia, a complex disorder characterized by bone marrow failure, chromosomal instability, and cancer susceptibility. In 2017, Haley moved back to Canada to open her lab in the Department of Biochemistry.

Research Lab

The Wyatt lab studies the structure, function, and regulation of nucleases. These enzymes are scissors that have critical roles in repairing damaged DNA and maintaining genome stability. We use a powerful combination of techniques in biochemistry and molecular biology, including protein expression and purification, enzymology, proteomics, microscopy, and phenotypic analyses of cultured human cells.

Research opportunities are available for enthusiastic, positive, and highly-motivated individuals that seek to understand how human cells maintain genome stability, and how protein dysfunction gives rise to human disease. Graduate students should apply directly to the Department of Biochemistry. Successful applicants will have the option to rotate through our lab prior to formal acceptance.

Check out our lab website for more information: https://haleywyatt2.wixsite.com/website.

Learn more: Wyatt Lab

Research Description

DNA Scissors, DNA Repair and Genome Stability

DNA Repair and Genome Stability

An essential component of every living organism is DNA, which provides the blueprint for life and is required for the biological processes in each and every cell. During normal cell growth, this genetic information must be accurately replicated and propagated to two daughter cells. Paradoxically, DNA is highly susceptible to damage by agents that occur naturally (e.g. metabolic by-products) and in the environment (e.g. ultraviolet radiation, carcinogenic chemicals). If left unrepaired, damaged DNA can trigger mutations, chromosomal rearrangements and genome instability. To counteract the deleterious effects of genotoxic agents, cells contain sophisticated DNA repair networks that safeguard genome integrity and ensure proper cell function. Understanding the intricate mechanisms that underpin these essential cellular pathways is a major goal of scientists that study the basic biological processes of DNA repair and genome stability.

DNA Scissors

Most DNA repair pathways require the actions of structure-selective endonucleases (SSEs), which are molecular scissors that remove potentially toxic DNA structures that form during DNA repair (and normal cell growth). The failure to remove these structures compromises chromosome stability. Nevertheless, DNA cleavage opens the door for indiscriminate repair that can fuel genetic rearrangements, emphasizing the importance of regulatory mechanisms to control the activity of SSEs and prevent uncontrolled DNA cleavage.

The conserved SSEs SLX1-SLX4, MUS81-EME1 and XPF-ERCC1 are required for DNA recombination and repair in most eukaryotes. The SLX4 protein provides a scaffold for the SMX tri-nuclease complex, formed by interactions with SLX1, MUS81-EME1 and XPF-ERCC1. SLX4 interacts with several other genome stability proteins, leading to the prevailing model that SLX4 provides a hub for the assembly of versatile macromolecular complexes that orchestrate diverse protein-DNA transactions. Key questions about the structure, function, and regulation of these complexes need to be addressed for a complete understanding of how these enzymes mediate genome stability.

Research Goals

The overarching aim of my lab is to elucidate the cellular roles, regulation and biochemical mechanisms of macromolecular SLX4 complexes. This information will provide a mechanistic framework for understanding how these complexes function and preserve genome integrity. This objective is inherently multi-disciplinary in nature and will ultimately involve structural, biochemical and cellular studies, thus providing an ideal training environment for researchers at all stages of their careers.

 

 

Awards & Distinctions

2017 - 2022 — NSERC Discovery Grant
2018 - 2023 — CIHR Project Grant
2018 - 2023 — Canadian Foundation for Innovation, John R. Evans Leaders Fund
2018-2023 — Ontario Ministry of Research, Innovation and Science Fund
2018-2023 — Canada Research Chair in Mechanisms of Genome Instability
2018-2020 — Connaught Early Researcher Award

Courses Taught

BCH374Y Research Project in Biochemistry
BCH473Y Advanced Research Project in Biochemistry

Publications

View all publications on PubMed