Many of the signaling pathways that are involved in development are also involved in the onset and progression of disease. As an example, the Wnt signaling pathway is required during many stages of development and in the homeostasis of stem cells in the adult. Perturbation of this pathway in stem cells in the adult often leads to cancer. It is now known that greater than 90% of colorectal cancers are caused by mutations in the Wnt signaling pathway. As this pathway is important for both proper development and disease, I am curious to know how this pathway can turn it self on and off so many times during development and why it fails to turn off in disease. The lab focuses on two negative feedback regulators of Wnt signaling: Nkd1 and Axin2.Learn More
My lab focuses on two main axes of research:
1) Unfolded Protein Response and Human Diseases: We study proteins that play key roles in animal stress responses, specifically the Unfolded Protein Response (UPR), which has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimer’s, diabetes, cancer and viral infection.
2) Molecular Mechanisms of Aging: We are working to establish planarians as a new aging model to test the hypothesis that longevity requires multiplex resistance to stress. We hope to identify genes or alleles that confer such multiplex stress resistance and/or promote longevity.
My lab aims to understand 1) the molecular genetic mechanisms of recombination in mammalian cells; 2) how defects in recombination contribute to tumorigenesis; and, 3) the nature of recombination hotspots. We are presently researching questions pertaining to: the mechanism and frequency of recombination in mammalian cells; the role of large palindromes in promoting recombination; mammalian heteroduplex DNA formation and repair; genetics of strand invasion and 3' end polymerization; how DNA sequences act to stimulate recombination; non-crossover mechanisms of homologous recombination; the genetic control of recombination.Learn More
Cell adhesion and migration are fundamentally important to the existence of multicellular organisms. This is obvious in light of the numerous diseases that can afflict humans when these processes are impaired. Disruption of normal cellular adhesive and migratory activities can lead to developmental disorders and contribute to the progression of arthritis, immunological deficiencies and cancer. Both cell adhesion and migration are complex processes involving numerous biochemical signalling events, reorganization of the cellular cytoskeleton and localized remodelling of the plasma membrane. It is the goal of my laboratory to elucidate the molecular mechanisms that link these activities, allowing them to be coordinated during changes in cell adhesion and motility.Learn More
Research in our laboratory is focused on defining eukaryotic signal transduction pathways, and investigating how mutations in components of these pathways can contribute to human disease. Signal transduction is a central process in multicellular organisms that allows for the exchange of informational cues between and within cells. Current areas of research include: 1) Signalling pathways controlling kidney podocyte morphology; 2) focal adhesion dynamics in cancer cells; and, 3) characterization of a novel neuronal adaptor protein, ShcD.Learn More
We currently have several projects in various areas that explore aspects of the gut microbiome and beyond:
1) Understanding how gut microbes are involved in the modulation of disease in colorectal cancer, diabetes, infection, and inflammatory bowel diseases
2) Isolation and characterisation of hunter-gatherer people's gut microbiome in an effort to discover novel microbial species and understand their function
3) Characterisation of the non-bacterial microbes of the human microbiome and their functions
4) Building model systems to study human gut microbes in vitro and in vivo
5) The study of 'oncomicrobes' (in particular, Fusobacterium nucleatum), and the development of colorectal cancer.
6) Translation to the clinic - development of 'microbial ecosystem therapeutics'
Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis consists of the eukaryotic translation initiation factor 4E (eIF4E) binding to the 5' cap of mRNAs. However, many cellular stresses repress cap-dependent translation to conserve energy by sequestering eIF4E. This raises a fundamental question in biology as to how proteins are synthesized during periods of cellular stress and eIF4E inhibition. Research in our laboratory will build upon the discovery that cells switch to an alternative cap-binding protein, eIF4E2, to synthesize the bulk of their proteins during periods of oxygen scarcity (hypoxia).Learn More
First, we have systematically generated inhibitors and activators for E3 ubiquitin ligases to discover new enzyme catalytic mechanism and new substrates. We continue to develop synthetic peptides and proteins to delineate biochemical mechanisms of E3 ubiquitin ligases.
Second, we showed that structure-based protein engineering enables development of anti-viral reagents for Middle East respiratory syndrome (MERS) coronavirus. Now we started engineering post-translational modifications to probe and rewire DNA damage signaling for cancer therapeutics.
Finally, we created molecular tools to increase CRISPR-Cas9 genome-editing efficiency. Now we are developing new tools as "off-switch" for CRISPR-based gene editing through targeted protein degradation.