Dr Alexander Sobinoff
Children's Medical Research Institute
Faculty of Medicine and Health
Dr Sobinoff is a Senior Research Officer at the Children’s Medical Research Institute and a Senior lecturer at the University of Sydney’s Faculty of Medicine and Health. He is a molecular and cellular biologist with over 10 years’ research experience focusing on telomere biology and DNA damage/repair. Dr Sobinoff’s research has helped define the modern Alternative Lengthening of Telomeres (ALT) field, creating new internationally recognised methods for measuring telomere extension and identifying the first viable therapeutic target for ALT cancers.
My research program involves gene discovery using functional genomics to characterise mechanisms of cancer cell telomere length maintenance and repair. Telomeres are specialised DNA-protein structures which differentiate the ends of linear chromosomes from sites of DNA damage. Telomeres shorten during each round of cell division, eventually triggering cellular senescence and apoptosis when they become critically short. As part of oncogenesis, cancer cells must activate a telomere maintenance mechanism to lengthen their telomeres and achieve cellular immortality. Paradoxically, cancer cells have several telomere deficiencies brought about by replication stress, resulting in fragile and damaged telomeres. These deficiencies represent a unique vulnerability that can be exploited for the treatment of cancer.
I am currently investigating the different DNA damage repair pathways that converge at telomeres in cancer cells and the role of RNA/DNA binding proteins in regulating telomerase activity. I am also testing the efficacy of several telomere-based cancer therapies, including novel telomere targeting peptides and chemical inhibitors designed to induce mitotic catastrophe specifically in ALT cancer cells. Approximately 10% of all cancers rely on the ALT pathway of telomere maintenance to achieve replicative immortality. This percentage is significantly higher (~60%) in bone and soft tissue sarcomas, glioblastomas, pancreatic neuroendocrine tumours, and high-risk neuroblastomas. Collectively, these cancers account for approximately 2,500 new cases in Australia annually, with 150-180 of these cases occurring in children (20-25% of all children’s cancer).
- Cancer cell biology
- Molecular biology
- Cellular biology
- DNA damage and repair
- The role of RNA binding proteins in the DNA replication stress response
- Investigating the role of a novel RNA binding protein in telomerase activity
- Cancer Institute NSW Early Career Fellow
- Australian Society for Medical Research
- The University of Sydney Cancer Research Network
- Kids Cancer Alliance
| Project title | Research student |
|---|---|
| Synthetic Lethality with FANCM inhibition in ALT-negative Cancer Cells | Jake SCHWENKE |
Publications
Book Chapters
- Sobinoff, A., Bernstein, I., McLaughlin, E. (2012). All Your Eggs in One Basket: Mechanisms of Xenobiotic Induced Female Reproductive Senescence. In Tetsuji Nagata (Eds.), Senescence, (pp. 559-584). Croatia: InTech.
- Sobinoff, A., McLaughlin, E. (2010). Contraception Targets in Mammalian Ovarian Development. In Ursula-F. Habenicht and R. John Aitken (Eds.), Fertility Control, (pp. 45-66). Heidelberg Dordrecht London New York: Springer. [More Information]
Journals
- Lu, R., Nelson, C., Rogers, S., Cesare, A., Sobinoff, A., Pickett, H. (2024). Distinct modes of telomere synthesis and extension contribute to Alternative Lengthening of Telomeres. iScience, 27(1). [More Information]
- Bruedigam, C., Porter, A., Song, A., Vroeg in de Wei, G., Stoll, T., Straube, J., Cooper, L., Cheng, G., Kahl, V., Sobinoff, A., Pickett, H., et al (2024). Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia. Nature Cancer, 5(1), 47-65. [More Information]
- Sobinoff, A., Pedone, P., Chambery, A., Cesare, A., Altucci, L., Pickett, H., Cosconati, S., Di Maro, S., Low, R., Benedetti, R., et al (2023). Irreversible inhibition of TRF2
TRFH recruiting functions by a covalent cyclic peptide induces telomeric replication stress in cancer cells. Cell Chemical Biology, 30(12), 1652-1665.e6. [More Information]
2024
- Lu, R., Nelson, C., Rogers, S., Cesare, A., Sobinoff, A., Pickett, H. (2024). Distinct modes of telomere synthesis and extension contribute to Alternative Lengthening of Telomeres. iScience, 27(1). [More Information]
- Bruedigam, C., Porter, A., Song, A., Vroeg in de Wei, G., Stoll, T., Straube, J., Cooper, L., Cheng, G., Kahl, V., Sobinoff, A., Pickett, H., et al (2024). Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia. Nature Cancer, 5(1), 47-65. [More Information]
2023
- Sobinoff, A., Pedone, P., Chambery, A., Cesare, A., Altucci, L., Pickett, H., Cosconati, S., Di Maro, S., Low, R., Benedetti, R., et al (2023). Irreversible inhibition of TRF2
TRFH recruiting functions by a covalent cyclic peptide induces telomeric replication stress in cancer cells. Cell Chemical Biology, 30(12), 1652-1665.e6. [More Information]
2022
- de Nonneville, A., Salas, S., Bertucci, F., Sobinoff, A., Adélaïde, J., Guille, A., Finetti, P., Noble, J., Churikov, D., Chaffanet, M., Pickett, H., Reddel, R., et al (2022). TOP3A amplification and ATRX inactivation are mutually exclusive events in pediatric osteosarcomas using ALT. EMBO Molecular Medicine, 14(10). [More Information]
2020
- Sobinoff, A., Pickett, H. (2020). Mechanisms that drive telomere maintenance and recombination in human cancers. Current Opinion in Genetics & Development, 60, 25-30. [More Information]
- Kahl, V., Allen, J., Nelson, C., Sobinoff, A., Lee, M., Kilo, T., Vasireddy, R., Pickett, H. (2020). Telomere Length Measurement by Molecular Combing. Frontiers in Cell and Developmental Biology, 8, 1-14. [More Information]
2019
- Perera, O., Sobinoff, A., Teber, E., Harman, A., Maritz, M., Yang, S., Pickett, H., Cesare, A., Arthur, J., Mackenzie, K., Bryan, T. (2019). Telomerase promotes formation of a telomere protective complex in cancer cells. Science Advances, 5(10), 1-14. [More Information]
- Lu, R., O'Rourke, J., Sobinoff, A., Allen, J., Nelson, C., Tomlinson, C., Lee, M., Reddel, R., Deans, A., Pickett, H. (2019). The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT). Nature Communications, 10(1), 1-14. [More Information]
2018
- Sutherland, J., Sobinoff, A., Fraser, B., Redgrove, K., Siddall, N., Koopman, P., Hime, G., McLaughlin, E. (2018). RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis. Journal of Cellular Physiology, 233(4), 3262-3273. [More Information]
2017
- Sobinoff, A., Pickett, H. (2017). Alternative Lengthening of Telomeres: DNA Repair Pathways Converge. Trends in Genetics, 33(12), 921-932. [More Information]
- Sobinoff, A., Allen, J., Neumann, A., Yang, S., Walsh, M., Henson, J., Reddel, R., Pickett, H. (2017). BLM and SLX4 play opposing roles in recombination-dependent replication at human telomeres. EMBO Journal, 36(19), 2907-2919. [More Information]
- Dagg, R., Pickett, H., Neumann, A., Napier, C., Henson, J., Teber, E., Arthur, J., Reynolds, C., Murray, J., Haber, M., Sobinoff, A., Lau, L., Reddel, R. (2017). Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres. Cell Reports, 19(12), 2544-2556. [More Information]
2015
- Killedar, A., Stutz, M., Sobinoff, A., Tomlinson, C., Bryan, T., Beesley, J., Chenevix-Trench, G., Reddel, R., Pickett, H. (2015). A Common Cancer Risk-Associated Allele in the hTERT Locus Encodes a Dominant Negative Inhibitor of Telomerase. PLoS Genetics, 11(6), 1-23. [More Information]
2014
- Sutherland, J., Fraser, B., Sobinoff, A., Pye, V., Davidson, T., Siddall, N., Koopman, P., Hime, G., McLaughlin, E. (2014). Developmental expression of Musashi-1 and Musashi-2 RNA-binding proteins during spermatogenesis: analysis of the deleterious effects of dysregulated expression. Biology Of Reproduction, 90(5), 92. [More Information]
2012
- Sobinoff, A., Bernstein, I., McLaughlin, E. (2012). All Your Eggs in One Basket: Mechanisms of Xenobiotic Induced Female Reproductive Senescence. In Tetsuji Nagata (Eds.), Senescence, (pp. 559-584). Croatia: InTech.
- Sobinoff, A., Nixon, B., Roman, S., McLaughlin, E. (2012). Staying alive: PI3K pathway promotes primordial follicle activation and survival in response to 3MC-induced ovotoxicity. Toxicological Sciences, 128(1), 258-271. [More Information]
2010
- Sobinoff, A., McLaughlin, E. (2010). Contraception Targets in Mammalian Ovarian Development. In Ursula-F. Habenicht and R. John Aitken (Eds.), Fertility Control, (pp. 45-66). Heidelberg Dordrecht London New York: Springer. [More Information]
Selected Grants
2017
- Targeting telomeric repeat-binding factor 2 TRF2 with small molecule inhibitors to promote a DNA damage response and prevent cancer cell growth, Sobinoff A, Pickett H, Cancer Institute NSW/Early Career Fellowship
2016
- Developing a rapid and quantitative telomere length test to measure chemotherapeutic response to telomerase inhibition, Sobinoff A, Cancer Australia/Priority Driven Collaborative Cancer Research Scheme