I. N-Myc transcriptional regulation of gene coding for
neurotrophin receptors (p75NTR, TrkA) and ABC (ATP Binding Cassete
Transporters) in neuroblastoma.
II. Set up and characterization of an animal model trhat recapitulates the mechanisms that cause a block of cell differentiation dependent on an excess of the MYC oncoprotein in a MAX-indepndent manner.
III. Set-up and characterization of an drosophila model of BcrAbl+
Leukemias for genetic and pharmacological screens (external advice;
in collaborazione con Prof. G. Saglio, Dr. D. Cillone e Dr. F.
Messa (divisione di Ematologia e Medicina Interna, Dipartimento di
Scienze Cliniche e Biologiche, Università di Torino, Orbassano
IV. In vivo analysis of the mechanism of action of a new
anti-leukemic drug class (SMO protein inhibitor) studied to
contrast the relapse in Chronic Myelogenous Leukemia
II. The Myc family is formed by three oncoproteins c-Myc, N-Myc and
L-Myc each able to heterodimerize with the Max-family factors and
to work as transcription factors. The identification of the Myc's
target genes is the key step to understand its role in cancer
biology and particularly in cancer where myc is amplified or
overexpressed. We have identified as putative Myc target genes the
ones coding for the neurotrophin receptors (p75NTR and TrkA) and
for some ABC (ATP Binding Cassette) transporters. We are currently:
i) defining how N-Myc regulates transcritpion of the above cited
genes in neuroblastoma cells; ii) Verifying that Myc controls
multidrug resistance especially in cancer stem-cells