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Papa Lab research

Collaborations | Student research projects | Publications

About Dr Antonella Papa

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 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 1500 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.


Our research

Current projects

  1. To define the functional role of PTEN catalytic activity in breast cancer
  2. To characterise the contribution of the mTOR signalling pathway to neoplastic transformation of glial cells

Visit Dr Papa's Monash research profile to see a full listing of current projects.

Research activities

The PI3K-Akt-mTOR cascade is a key intracellular signalling pathway that mediates several biological processes including cell growth, proliferation, metabolism and cytoskeleton reorganisation. As such it is not surprising that mutations in key regulators of this pathway are frequently associated with cancer. PTEN (phosphatase and tensin homologue deleted 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.

We apply a combination of in vitro studies and in vivo analyses and use 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 more effective treatments of human diseases, including cancer.

Figure 1. Cartoon depicting natural tumour evolution. 

Honours Projects

1. Validation of candidate Pten-targets: We have performed phosphoproteomics of primary cells derived from two knock-in mouse lines harbouring loss-of-function and cancer-associated mutations in Pten. These mutations differentially affect the lipid or the lipid-and-protein Pten phosphatase activities and as a result their expression induces activation of distinct signalling pathways. This project aims to validate the activation status of newly identified Pten-regulated pathways and requires the execution of a number of experiments including: i) expansion, treatment, and purification of human and mouse cell lines; ii) protein analyses; and iii) gene expression profiling.

2. Mammary gland morphology and tumour onset of mutant mice:  We have generated new mouse models expressing mutant version of Pten in combination with additional oncogenic mutations and this has resulted in rapid mammary tumour formation. To characterise tumour onset and assess how alterations in the mammary gland development contributes to tumour formation, we plan to collect fat pads from experimental and control mice and study branching morphogenesis and evolution of epithelial buds. This projects requires working with animal models, processing of mouse tissues, and a number of immunostaining techniques.

Carmine alum-stained wholemount of 12 weeks old mammary gland.


Techniques/expertise

  • Mouse model of human cancer
  • Tissue analyses (e.g. immunohistochemistry; immunofluorescence; DNA, RNA, and protein extraction)
  • Molecular biology (e.g. small and large scale protein analyses; cDNA cloning and mutagenesis)
  • Tissue culture (e.g. primary murine cell purification and expansion; human and mouse cancer cell lines)

Disease models

  • Breast cancer
  • Metabolic syndrome
  • Brain and neurodevelopmental disorders

Collaborations

We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).


STUDENT RESEARCH PROJECTS

The Papa Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact Dr Antonella Papa regarding potential projects that align with the presented research themes.