Meet our PostDocs

Trost

Brett Trost, PhD

Supervisor 

Stephen Scherer, Senior Scientist, Genetics and Genome Biology, Hospital for Sick Children and University Professor, Department of Molecular Genetics, University of Toronto.

Thesis

Dr. Trost’s PhD thesis, “Design and Data Analysis of Kinome Microarrays”, describes computational methods that facilitate the creation and use of kinome microarrays, a technology for studying how cells communicate. Specifically, his thesis describes two novel algorithms, called DAPPLE and PHOSFER, for designing kinome microarrays, as well as a new statistical method, PIIKA, for accurately analyzing data from these arrays. DAPPLE, PHOSFER, and PIIKA have been used by the United States National Institutes of Health to study the Ebola, Pichinde, and monkeypox viruses, with the results suggesting potential treatments for these infections. They have also been applied to numerous other problems in human health (breast cancer; medulloblastoma; cystic fibrosis; arthritis) and agriculture (colony collapse disorder in honeybees; Johne's disease in cattle; fungus infection in soybeans; and Salmonella infection in chickens). All three methods are freely available on the internet and have collectively been used thousands of times by hundreds of unique users. Dr. Trost received several prestigious awards for his thesis work, including the University of Saskatchewan PhD Thesis Award and the Governor-General’s Academic Gold Medal.

Dr. Trost’s postdoctoral research has focused on the detection and interpretation of genetic variants associated with human disease. The first study led by Dr. Trost during his postdoctoral fellowship developed a workflow for accurately detecting copy number variants (large deletions or duplications of genetic material) from human whole-genome sequencing data. Published in the American Journal of Human Genetics, this workflow has recently been used to identify pathogenic genetic variants in more than 20,000 individuals with autism and their family members. In addition, Dr. Trost’s workflow is now a standard component of the genomic analysis pipeline used by The Centre for Applied Genomics, Canada’s largest DNA sequencing centre, where it is applied to thousands of genomic samples every year. Dr. Trost has also been involved in a wide range of other exciting projects during his postdoctoral fellowship, including the sequencing of the Canadian beaver genome; an evaluation of blood, saliva, and cheek-swab samples for DNA sequencing; the whole-genome sequencing of healthy individuals as part of Canada’s Personal Genome Project; and studies providing insight into the genetics of heart disease, Huntington’s disease, and metabolic disorders.

Previously, tandem repeat expansions have been associated with many diseases, most famously Huntington’s disease, but they had never before been associated with a disorder with complex genetics like autism. In a study published last year in Nature, Dr. Trost working under study-lead Dr. Ryan Yuen (Assistant Professor in the Department of Molecular Genetics), showed that tandem repeat expansions may account for up to 2.6% of autism cases, opening the door to many avenues of further research, both in autism and in other diseases with complex genetics.

Dr. Trost has received numerous prestigious awards during his postdoctoral fellowship, including the Hospital for Sick Children Lap-Chee Tsui Fellowship for Research Excellence, the Canadian Open Neuroscience Platform Research Scholar Award, and the CIHR Banting Postdoctoral Fellowship, for which ranked in the top 2% of applicants across Canada. He was also one of approximately 600 young scientists worldwide selected to attend the 2018 Lindau Nobel Laureate Meeting, which was attended by nearly 40 Nobel Laureates.

Although genome sequencing is becoming more and more widespread, the function and regulation of the human genome remain poorly understood. Upon completion of his postdoctoral fellowship, Dr. Trost plans to start his own laboratory dedicated to using computational and statistical methods for advancing our understanding of the genetics of human disease.

Glynnis DuBois

Glynnis E. DuBois, PhD

Supervisor

Professor Monika Molnar

Thesis

Using Group Music Activities with Families to Support School-Readiness Skills in Preschool Children with Hearing Loss.”

This thesis reviewed the challenges faced by children with hearing loss and their families at school entry and explored how to support school readiness skills using music as a medium. A music and movement curriculum was developed using Neurologic Music Therapies. This was then used in a twelve-week intervention with preschool children and parent participants. Both pre and postintervention standardized testing was used as well as a postintervention parent interview. Results for the addition of this kind of group intervention to support areas of development and provide ongoing strategies and resources for this population was promising.

Two manuscripts were published from this thesis and during the course of the PhD, three book chapters were co-authored.

4. This postdoc project is a collaborative validation study. It involves a new artificial intelligence (AI) powered application developed by ‘Babbly’ which tracks communication during the babbling stages of babies 6-18 months of age. This convenient app, once validated, could be used by clinicians to compare speech and language development to known benchmarks in typically developing children. Families will be able to upload audio/videos of their baby’s communicative interactions and the app will analyze the communication progression over time.

Once validated, the AI will be used to compare datasets of typically developing babies to those at risk for atypical development to identify any differences between the groups in terms of type, frequency, or length of utterance. Any deviations from typical developmental trajectories could then be flagged facilitating early referral and assessment. The goal is to enable the earliest identification of language delays in Canadian children.

This project is funded for two years by the Mitacs Elevate program.

Kimberley Gauthier

Kimberley Gauthier, PhD

Supervisor:

Dr. Julie Brill, Senior Scientist, Cell Biology Program, The Hospital for Sick Children, and Professor, Department of Molecular Genetics, University of Toronto

PhD Thesis Title:

In vivo analysis of the LIN-2/7/10 complex in spatial regulation of LET-23 EGFR signalling C. elegans

PhD Thesis Summary:

Scaffolding proteins play a central role in spatial regulation of signaling cascades, which ensures proper timing, localization, and activation of signaling during development. The nematode Caenorhabditis elegans relies on polarized localization of the Epidermal Growth Factor Receptor (EGFR), a receptor tyrosine kinase that is frequently overactivated in human cancers, for normal signaling activation and cell fate specification during vulva development. During my PhD, I studied the mechanism through which an evolutionarily conserved complex consisting of LIN-2 (CASK), LIN-7 (Lin7a), and LIN-10 (APBA1) (the LIN-2/7/10 complex) maintains EGFR localization to ensure normal vulva development. My research revealed novel Golgi-associated pathways through which these proteins work both as a complex, and also independently of each other, to coordinate polarized trafficking, cell signaling, and development.

Current Research:

During the development of a multicellular organism, epidermal tissue wraps around the embryo and forms a seamless seal, resulting in a continuous epithelial sheet. A prime example is dorsal closure in Drosophila, a fruit fly model organism, in which lateral epidermal cells wrap around the developing embryo and join together along its back. Dorsal closure is driven by similar cellular mechanisms as wound healing: activation of the Jun Kinase (JNK) signaling pathway, and contractions of the actin cytoskeleton (structural filaments that control cell shape and movement of structures and proteins within a cell). Still, our understanding of how cells synchronize their movements and coordinate cellular processes to seal up a hole in an epithelial sheet is incomplete. Work from the Brill and Harden labs found that lipid phosphatase Sac1 is necessary for dorsal closure, possibly due to its requirement for restricted JNK signaling, myosin expression, and cytoskeleton contractility. Throughout my postdoctoral work, I will study the role of Sac1 and of phospholipids during dorsal closure in Drosophila by testing how Sac1 activity is regulated, the mechanism through which Sac1 inhibits JNK signaling, and how Sac1 coordinates cytoskeletal function. These studies will uncover key requirements for phospholipid regulation in mediating cellular and tissue dynamics during development.

Scholarships/Awards:

My graduate research was supported by Master’s and Doctoral scholarships from the Fonds de Recherche du Québec – Santé (FRQS), by a Master’s Canada Graduate Scholarship from the National Science and Engineering Research Council (NSERC), and a Doctoral Post-Graduate Scholarship from NSERC.

Publications:

  1. Gauthier KD, Rocheleau CE (2021). Dynamic expression and localization of the LIN-2/7/10 protein scaffolding complex during C. elegans vulval development. Development, 148: dev194167 doi: 10.1242/dev.194167
  2. Gauthier KD, Rocheleau CE (2021). LIN-10 can promote LET-23 EGFR signaling and trafficking independently of LIN-2 and LIN-7. Mol Biol Cell, doi:1-.1091/mbc.E20-07-0490.
  3. Gauthier K, Rocheleau CE (2017). C. elegans Vulva Induction: An In Vivo Model to Study Epidermal Growth Factor Receptor Signaling and Trafficking. In: Wang Z. (eds) ErbB Receptor Signaling. Methods in Molecular Biology, vol 1652. Humana Press, New York, NY.
  4. Skorobogata O*, Meng J*, Gauthier K, Rocheleau CE (2016). Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling. Mol Biol Cell, doi:10.1091/mbc.E15-11-0757.
  5. Hoang C, Ferraro-Gideon J, Gauthier K, Forer A (2013). Methods for rearing Mesostoma ehrenbergii in the laboratory for cell biology experiments, including identification of factors that influence production of different egg types. Cell Biol Int, 37(10): 1089-1105.
Meryem Baghdadi

Meryem Baghdadi, PhD

Supervisor: 

Scientist, Developmental & Stem Cell Biology Program - The Hospital for Sick Children-Assistant Professor, Department of Molecular Genetics - University of Toronto

PhD thesis: 

Regulation of adult muscle stem cell quiescence by Notch signalling

Meryem completed her PhD at Institut Pasteur (Paris, France) and joined the Dr. Tae-Hee Kim Lab in November 2018 at SickKids.  Her research focus on glial cells, one of the most abundant cell types of the intestine and Inflammatory Bowel Disease (IBD). IBD is an umbrella under which live a number of chronic inflammation disorders in the small or large intestine that induce symptoms like pain, weight loss and diarrhea. All of these make everyday life for patients difficult. Canada has one of the highest IBD incidence rates in the world (1/140 Canadians) and an alarmingly increasing prevalence, especially in infants and children. The intestine is the most highly regenerative organ in the human body as it undergoes constant wear and tear while breaking down food, absorbing nutrients, and eliminating waste. This repair is maintained by resident intestinal stem cells that generate all the different cells type of the gut. To function properly, stem cells need to receive appropriate signals from their environment. If those signals are altered, it can lead to disease, including IBD. Glial cells are located in close physical proximity to stem cells, but their potential interactions are currently unknown. She investigates how glial cells can modulate stem cell behavior under normal conditions, during repair (after injury), and in chronic inflammation. Compiling analysis from a model of IBD created in mice, and from human glial cells from healthy and IBD patients, will reveal the role of glial cells in IBD and inform new targets for drug development and treatment. Improving stem cell response, through glial cells, in the early stage of the disease could enhance intestinal healing and thus prevent and/or alleviate the inflammation, especially in children, reducing or eliminating the human and healthcare costs of IBD in Canada and the world.

Meryem started her postdoc funded by SickKids Restracomp postdoctoral fellowship (William P. Wilder Fund Bursary) and is now holding the highly competitive CIHR postdoctoral fellowship for 3 years.

Meryem published 5 manuscripts (including a first author in Nature and Cell Stem Cell) and is currently working on the revisions of her first postdoc manuscript. Her PhD and postdoctoral trainings converge towards the regulation of the stem cell niche during homeostasis, repair and pathology in two different models: the skeletal muscle and the intestine. After completing her postdoctoral training, she would like to become a principal investigator at a competitive and stimulating academic research institute and continue to investigate stem cell niche interactions in different contexts such as aging or tumorigenesis