John DiGuglielmo
Associate Professor, Acting Graduate Program Chair BSc Biochemistry at McGill University Office: Medical Sciences Building 228
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Why Science?
I chose to go into science during my undergraduate degree because I was always interested in figuring out how things worked. I especially enjoyed learning about the inner workings of the cell, and how cells communicate with different systems in the body. I first realized that I was interested in pursuing research while I was doing an independent research project in Cell Biology, which is equivalent to the 4th year research projects in our department. I appreciated how my supervisor gave me the opportunity to be independent and explore a specific research question. This was also my first immersion into carrying out research on a daily basis. I found that I enjoyed research and interacting with people in the lab. This experience really sparked my interest in academia because I saw my supervisor’s daily routine as well. There was never two days in a row that were exactly the same, as he would lecture, attend meetings, work on manuscripts and/or grants, etc.
Research Goals:
My lab is working on mechanisms of how epithelial cells undergo processes to become tumourigenic. One cytokine that we work with is Transforming Growth Factor Beta (TGFβ), which can do two things once it is bound to its receptor. In normal cells, it causes apoptosis of cells to keep epithelial cells in check. However, once mutations accumulate in the cells, the cells start to respond to TGFβ differently. Instead of stopping the growth of cells, it begins to promote metastasis through the process of epithelial to mesenchymal transition. Cancer has a lot of the same aspects as uncontrolled wound healing, as TGFβ is involved in both. We want to understand the switch and how we can stop and understand it in terms of cellular mechanisms.
Specific Research Interests:
- We want to figure out the subcellular trafficking of TGFβ receptors and their regulation within the normal cell, as well as the tumour cell. We hope to figure out how to block the signalling in a tumour cell without interfering with signalling in a normal cell.
- We also want to understand how TGFβ feeds into autophagy. Autophagy and endocytosis have various common intermediates and processes between them, and we wish to tease out how these processes alter TGFβ signaling to promote EMT and tumorigenesis.
Our lab makes use of immunofluorescence microscopy, Western blotting, subcellular fractionation, gene silencing, and pharmacological inhibition to explore endocytosis, autophagy, and trafficking within the cell.
Undergraduate Teaching:
Physiol 3140A: Cellular Physiology - lecturer and course manager
Pharm 4360B: Mechanisms of Cancer Chemotherapy – lecturer
Physiol 4520B: Stem Cell Biology & Regenerative Medicine – lecturer
Physiol/Pharm 4980E: Seminar and Research Project – lab supervisor
Most Rewarding Moments:
Rewarding moments have changed throughout my career. At first, they were personal achievements; getting my first position at the university, being awarded my first research grant, publishing our independent laboratory’s first manuscript, etc. However, over the years, the most satisfying moments have shifted to participating and witnessing the success of my trainees. Indeed, I am very proud that so many of my trainees have gone on to successful careers in medicine, industry, and academia.
Advice to Students:
One piece of advice that I have for students who may be interested in research is to try to carry out an independent research project, either as part of a formal course or as a summer student. That way they can work in a lab full-time without other major distractions. The immersive experience will be a good indication of whether one will enjoy carrying out research.
Interests Outside of Academia:
Outside of academia, I enjoy reading, and learning how to play piano and guitar. I also enjoy designing and 3D printing items needed around the lab or home.
Awards and Recognitions:
UWO Dean’s Awards of Excellence for Undergraduate education (2018)
Highlighted Publications:
Trelford CB, Di Guglielmo GM. (2021) Canonical and Non-canonical TGFβ Signaling Activate Autophagy in an ULK1-Dependent Manner. Front Cell Dev Biol. 2021 Oct 25;9:712124. doi: 10.3389/fcell.2021.712124. eCollection 2021.
Wojtowicz S, Lee S, Chan E, Ng E, Campbell CI, Di Guglielmo GM. (2020) SMURF2 and SMAD7 induce SARA degradation via the proteasome.Cell Signal. 2020 Aug;72:109627. doi: 10.1016/j.cellsig.2020.109627. Epub 2020 Apr 10.
To C, Roy A, Chan E, Prado MAM, Di Guglielmo GM. (2017) Synthetic triterpenoids inhibit GSK3β activity and localization and affect focal adhesions and cell migration.Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1274-1284. doi: 10.1016/j.bbamcr.2017.03.012.
Chan E, Saito E, Honda T and Di Guglielmo GM. (2016) The acetylenic tricyclic bis(cyano enone), TBE-31, targets microtubule dynamics and cell polarity in migrating cells. Biochim Biophys Acta. 1863:638-49.
Adrian Gunaratne, Eddie Chan, Tarek El-Chabib, David Carter, and Gianni M Di Guglielmo (2015) aPKC alters TGFβ response in NSCLC cells via both Smad-dependent and Smad-independent pathways J. Cell Science 128:487–98.