BRIEF DESCRIPTION OF RESEARCH PROJECTS
A. ErbB family of receptor tyrosine kinases.
1. One goal of our studies is to understand the role of growth factors and their receptors in neurodegenerative diseases.
2. Recently we have found that ErbB receptors interact with nucleolin via their cytoplasmic tail. Since ErbBs, Ras and nucleolin were implicated in cancer formation, our hypothesis is that the interaction between these proteins enhances cell transformation. Thus our goal is to study the crosstalk between ErbB receptors, nucleolin and Ras and the involvement of this interaction in malignant transformation.
B. Autophagy and Beclin 1 and neurodegeneration
1. Autophagy in neurodegeneration. Autophagy is a process of regulated turnover of cellular constituents that in some cases may lead to Type II cell death. Defects in autophagy are linked to neurodegenerative diseases and cancer. We propose to further study the involvement of autophagy in neurodegenerative diseases and to substantiate our findings of rapamycin treatment as a valuable neuroprotective drug.
2. Beclin 1 interacting proteins and autophagy. Beclin 1, a Bcl-2-interacting protein, represents a potentially important junction of the apoptotic and autophagic machinery, and as such it interacts with proteins important for autophagy, such as Vps34, UVRAG, Ambra1, as well as with anti-apoptotic proteins such as Bcl-2. Recently, using GST pull-down assay and mass spectroscopy analysis we identified new Beclin1 interactions. Our results indicate that Beclin 1 may also interact with nonmuscle myosin heavy chain IIB (NMHC-IIB) and it also self interacts. We therefore propose to further study the involvement of Beclin 1, via its interactions with other proteins, to regulate autophagy/apoptosis in various cell types.
3. Autophagy as pro-oncogenic process. Recently we have found that found that Ras inhibition by Salirasib (FTS) induces autophagy in several cancer cell lines. The autophagy induced by FTS seems to protect cells from FTS induced cell death since in the absence of autophagy cell death is enhanced by FTS treatment. Thus we suggest that autophagy inhibition may promote FTS-mediated tumor cell growth inhibition. We will further study the protective effect of autophagy following treatments with anti cancer drugs. We expect that the combined treatment (with autophagy inhibitor and anti cancer drugs) may lead to enhanced cell growth inhibition and cell death and may lead to development of better future treatment.
