Projects per year
Personal profile
Research interests
Cancer is a complex disease that evolves over time and becomes more malignant by acquiring multiple genetic alterations.
The PI3K-Akt-mTOR cascade is a key intracellular signalling pathway that mediates several biological processes including cell growth, proliferation, metabolism and migration. As such it is not surprising that mutations in key regulators of this pathway are frequently associated with cancer. PTEN (phosphatase and tensin homology on chromosome 10) is a major negative regulator of the PI3K-Akt-mTOR pathway and is frequently inactivated or silenced in a range of human cancer and cancer syndromes.
The research in the Papa lab focuses on the identification and characterization of signalling pathways and molecular networks responsible for the correct functioning of cells in mammals with a special focus on the tumour suppressor PTEN.
Through a combination of in vitro studies and in vivo analyses, the Papa lab utilises recently generated mouse models to investigate how loss of PTEN functions alters normal cell behaviour to promote uncontrolled cell growth and survival, at a systemic level and in a tissue specific manner. The final goal of these studies is to identify new therapeutic targets for the development of novel treatments or treatment modalities of human diseases, including cancer.
Biography
Dr Antonella Papa received her PhD in Cellular Biology and Physiology working in the laboratory of Prof Della Valle, Department of Biology, University of Bologna, Italy. As PhD student Antonella worked on the functional role of Neurotrophin receptors TrkA and p75NTR in the regulation of neuronal differentiation and cell death implicated in Neuroblatoma development and Alzheimer’s disease (Exp Cell Res, 2007; Cancer Research, 2011).
In 2008 Antonella joined the laboratory of Prof Pier Paolo Pandolfi at the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA, USA, for her post-doctoral training. During that time she worked on the functional characterisation of mouse models with single and compound loss of tumour suppressors such as Pml, Tsc2, p53, and more predominantly with the phosphatase Pten. Antonella primary focus was on the in vivo phenotyping and functional characterisation of novel molecular mechanisms underlining Pten loss-of-function-driven tumourigenesis. Through her work she has established a new working model for the regulation and function of this essential tumour suppressor and published a research article as sole first author in Cell, 2014. As postdoc fellow, Antonella contributed to the development of new pre-clinical trials for the treatment of mouse models of breast and prostate cancer through single and combinatorial targeting of oncogenic pathways such as the PI3K-Akt-mTOR signalling pathway and the DNA damage response pathway (Cancer Discovery 2012, and 2014). In addition, she established several collaborations with many independent laboratories and published as co-author in several high impact journals including Nature, Cell Stem Cell, EMBO Mol Medicine, and Blood, with over 1200 citations in the last 5 years.
In late 2014, Antonella joined the Dept. of Biochemistry and Mol. Biology at Monash University where she has established her own lines of research focused on the identification of the molecular mechanisms driving breast and brain cancer formation and associated with mutations in members of the PI3K pathway.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Research area keywords
- Signal Transduction
- Cancer Biology
- PI3K pathway
- PTEN
- Breast Cancer
Collaborations and top research areas from the last five years
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Optimising combination therapies for breast cancer
Papa, A., Yip, K. & McLean, C.
19/03/21 → 18/06/25
Project: Research
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Targeting the cell cycle machinery for Alpelisib-resistant breast cancer cells
Suriyasena, S. & Papa, A.
Project: Research
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Targeting therapy-induced senescence to treat breast cancer
Papa, A. & Shamizadeh, M.
10/01/22 → 25/02/22
Project: Research
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Cabrini Hospital/Monash Biomedicine Discovery Institute (BDI) Breast Cancer Project
Richardson, G. E. (Primary Chief Investigator (PCI)), Abud, H. (Chief Investigator (CI)), Daly, R. (Chief Investigator (CI)), Mitchell, C. (Chief Investigator (CI)), Jarde, T. (Chief Investigator (CI)), Papa, A. (Chief Investigator (CI)), Lang, T. (Chief Investigator (CI)), Kerr, G. (Chief Investigator (CI)), Gregory, P. (Chief Investigator (CI)) & Vereker, M. (Chief Investigator (CI))
1/07/18 → 30/06/19
Project: Research
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Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer
Juvekar, A., Burga, L. N., Hu, H., Lunsford, E. P., Ibrahim, Y. H., Balmañà, J., Rajendran, A., Papa, A., Spencer, K., Lyssiotis, C. A., Nardella, C., Pandolfi, P. P., Baselga, J., Scully, R., Asara, J. M., Cantley, L. C. & Wulf, G. M., Nov 2012, In: Cancer Discovery. 2, 11, p. 1048-1063 16 p.Research output: Contribution to journal › Article › Research › peer-review
Open Access383 Citations (Scopus) -
The PTEN tumor suppressor forms homodimers in solution
Heinrich, F., Chakravarthy, S., Nanda, H., Papa, A., Pandolfi, P. P., Ross, A. H., Harishchandra, R. K., Gericke, A. & Losche, M., 2015, In: Structure. 23, 10, p. 1952 - 1957 6 p.Research output: Contribution to journal › Article › Research › peer-review
31 Citations (Scopus) -
Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function
Papa, A., Wan, L., Bonora, M., Salmena, L., Song, M., Hobbs, R. M., Lunardi, A., Webster, K., Ng, C., Newton, R. H., Knoblauch, N. W., Guarnerio, J., Ito, K., Turka, L. A., Beck, A. H., Pinton, P., Bronson, R. T., Wei, W. & Pandolfi, P. P., 2014, In: Cell. 157, 3, p. 595 - 610 16 p.Research output: Contribution to journal › Article › Research › peer-review
232 Citations (Scopus) -
Compound In Vivo Inactivation of Pml and p53 Uncovers a Functional Interaction in Angiosarcoma Suppression
Papa, A., Cordon-Cardo, C., Bernardi, R. & Pandolfi, P. P., 2012, In: Genes & Cancer. 3, 9-10, p. 599-603 5 p.Research output: Contribution to journal › Article › Research › peer-review
4 Citations (Scopus) -
Pml represses tumour progression through inhibition of mTOR
Bernardi, R., Papa, A., Egia, A., Coltella, N., Teruya-Feldstein, J., Signoretti, S. & Pandolfi, P. P., May 2011, In: EMBO Molecular Medicine. 3, 5, p. 249-257 9 p.Research output: Contribution to journal › Article › Research › peer-review
Open Access20 Citations (Scopus)