- Role: Postdoctoral ScientistGroup: Germline Stem Cell Biology
Dr Ai-Leen Chan is a Postdoctoral Scientist in the Germline Stem Cell Biology Group led by Associate Professor Robin Hobbs at the Centre for Reproductive Health, Hudson Institute of Medical Research. She is also an Adjunct Research Fellow at the Australian Regenerative Medicine Institute, Monash University.
Dr Chan’s research investigates molecular mechanisms underlying the maintenance of adult stem cells. This is often dependent on a resident population of stem cells that have the ability to self-renew and generate differentiating daughter cells. As a model system, she studies germline stem cells from the mouse testis that are essential for life-long production of spermatozoa and fertility. Appropriate control of stem cell self-renewal and differentiation is critical for tissue homeostasis while disruption of the balance between these processes can contribute to tissue degeneration or cancer.
Dr Chan completed her PhD at the Peter MacCallum Cancer Centre. She studied the regulation of tumour suppressors in prostate and colon cancers. Using xenograft mouse models, she demonstrated that down-regulation of E3 ligase E6AP prevents tumour initiation and growth by restoring PML tumour suppression function. She also identified the regulation of E6AP through phosphorylation by the tyrosine kinase c-Abl in response to stress. These studies highlight the therapeutic potential of E3 ligases in tumour suppression. She has also collaborated with Cancer Therapeutics to convert a lab-based assay that measures E3 ligase activity into a high-throughput screen.
Besides her research work, Dr Chan is actively involved in representing Early Career Researchers at Hudson. She works closely with the post-graduate student committee to coordinate the PhD-ECR mentoring program.
Chan AL, La H, Legrand J, Makela J, Eichenlaub M, De Seram M, Ramialison M, Hobbs RM (2017) Germline stem cell activity is sustained by SALL4-dependent silencing of distinct tumor suppressor genes. Stem Cell Reports 9:1-16.
Legrand J, Chan AL, La H, Rossello F, Anko M, Fuller-Pace F, Hobbs RM (2019) DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia. Nature Communications 10 (1):2278.
La H, Chan AL, Legrand J, Rossello F, Gangemi C, Papa A, Cheng Q, Morand E, Hobbs RM (2018) GILZ-dependent modulation of mTORC1 regulates spermatogonial maintenance. Development 145 (18).
La H, Makela J, Chan AL, Rossello F, Nefzger C, Legrand J, De Seram M, Polo J, Hobbs RM (2018) Identification of dynamic undifferentiated cell states within the male germline. Nature Communications 9 (1):2819.
Sinha D, Murugan K, Bowles J, Chan AL, Merriner D, Bain A, Simmons J, Freire R, Lopez, J, Hobbs R, O’Bryan M, Khanna K (2018) Cep55 overexpression causes male-specificity sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling. FASEB 32 :4984-4999.
Chan AL, Grossman T, Zuckerman V, Campigli Di Giammartino D, Moshel O, Scheffner M, Monahan B, Pilling P, Jiang YH, Haupt S, Schueler-Furman O, Haupt Y (2013) c-Abl phosphorylates E6AP and regulates its E3 ubiquitin ligase activity. Biochemistry 52(18):3119-3129.
Raghu D, Piotr P, Gulati T, Deb S, Khoo C, Russo A, Gallo E, Blandino G, Chan AL, Takano E, Fox S, Williams S, Haupt S, Gamell C, Haupt Y (2017). E6AP promotes prostate cancer by reducing p27 expression. OncoTarget 8(26):42939-42948.
Piotr P, Raghu D, Chan AL, Gulati T, Lambeth L, Takano E, Herold M, Hagekyriakou J, Vessella R, Fedele C, Shackleton M, Williams E, Fox S, Williams S, Haupt S, Gamell C, Haupt Y (2016) Restoration of tumor suppression in prostate cancer by targeting the E3 ligase E6AP. Oncogene 35(48):6235-6245.
Birch SE, Kench JG, Takano E, Chan P, Chan AL, Chiam K, Veillard AS, Stricker P, Haupt S, Haupt Y, Horvath L, Fox SB (2014) Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death. Annals of Oncology 25(12):2392-2397.
Wolyniec K, Chan AL, Haupt S and Haupt Y (2012) Restoring PML tumor suppression to combat cancer. Cell Cycle 11(20):3705-3706.