Prof. Dr. Rer. Nat. Natalia Pellegata

For over 2 decades, Natalia’s research projects focused on the elucidation of the molecular mechanisms involved in neuroendocrine tumors (NETs) development/progression, on the genetic predisposition to NETs and on the identification of novel therapeutic targets for these tumors. Natalia exploited novel and unique animal models in translational studies aimed at evaluating novel therapies against NETs based on their genetic profiles (precision medicine).

Capitalizing on the discovery that mutation of Cdkn1b (encoding p27) causes a Multiple Endocrine Neoplasia (MEN) syndrome in the rat (named MENX), Natalia identified the first patient with multiple endocrine tumors carrying a germline mutation in CDKN1B. These and subsequent studies established CDKN1B as novel tumor susceptibility gene for multiple NETs, and led to the definition of a new MEN syndrome in man (MEN4) cause by p27 mutations (PMID: 17030811; article cited >450 times). Given that animal models recapitulating human NETs and suitable for preclinical studies are scarce, Natalia has endeavored to characterize MENX-associated NETs at various levels (pathological, physiological, molecular) and could show that rat NETs quite faithfully recapitulate their human cognate tumors. Rat pheochromocytomas (PCCs) and nonfunctioning pituitary tumors (NFPTs) share genetic signatures, histomorphological, biochemical and physiological features with their cognate human tumors, attesting that rat NETs can be exploited as to gene discovery. Thus, starting from transcriptome data of the rat tumors, Natalia’s group found a new druggable pathway (BMP signaling) active in both rat and human PCCs. Along the same lines, her group recently demonstrated that the angiopoietin/Tie2 pathway is present in pituitary tumor cells (rat and human) and represents a promising target for therapy, as demonstrated by proof-of-principle in vivo studies. Natalia also exploited the MENX rat model for preclinical therapy-response studies to evaluate new drugs for efficacy against NETs, and provided the rationale for clinical implementation of dual PI3K/mTOR inhibitors and anti-angiogenic drugs in pituitary tumors and PCC. Being part of an SFB focusing on imaging for tumor monitoring for 12 years, she established important collaborations to apply functional imaging modalities to follow tumor response to various drugs in vivo.