POST DOC area neuro in Humanitas University

Research Program Title

Elucidating the pathomechanisms by which PAM mutations predispose to pituitary neuroendocrine tumors (PitNETs) formation

PI

Giampaolo Trivellin

Objectives of the research

Background: Pituitary neuroendocrine tumors (PitNETs) impact health via hormonal hypersecretion and brain invasion, with most cases lacking known driver mutations. We recently identified germline mutations in the PAM gene in PitNET patients. PAM, a multifunctional protein, regulates hormone amidation and secretion, with altered expression linked to cancer mortality.

Hypothesis: PAM defects predispose to PitNETs by disrupting its non-catalytic functions, unveiling a novel disease mechanism.

Aims: We aim to elucidate how PAM loss drives pituitary tumorigenesis via three approaches:

1. Investigate how PAM mutations affect intracellular pathways and hormone secretion in tumor cell lines.

2. Study pituitary-specific PAM loss in mice to assess tumorigenesis and systemic effects.

3. Evaluate PAM staining as a biomarker in human PitNETs.

Expected Results: Our findings will reveal PAM’s non-enzymatic roles in PitNET development, provide systemic insights, and assess PAM as a diagnostic/prognostic tool, advancing genetic testing and early diagnosis.

Activities to be carried out

The work will include:

• Mammalian cell culture, including performing functional studies of different genetic mutations;
• establishing and phenotyping mouse models.

Work place

PIEVE EMANUELE - Milan

Mandatory requirements

• Master degree in Biology, Molecular Biology, Medical, Industrial, veterinary and pharmaceutical biotecnologies,
•  PhD or equivalent;
• Adequate scientific and professional background to carry out the research activity described in this call.

Selection criteria

Selection criteria are predetermined by the Selection Committee. As part of the selection process, the Committee will evaluate the curriculum, titles and publications presented by the candidate and in particul will consider:

• Good knowledge of the English language,
• experience with molecular biology techniques and mammalian cell culture,
• experience in working with mouse models.