Direcții de cercetare

A. DIRECȚII DE CERCETARE - STUDENȚI

(teze de licență, de disertație, de doctorat)

1. ErbB proteins and cancer

The epidermal growth factor (EGF) family of receptor tyrosine kinases (TKs) contain 4 members HER1 (EGFR/ErbB1), HER2 (ErbB2, neu), HER3 (ErbB3), and HER4 (ErbB4) and they play important roles in differentiation, apoptosis and cell proliferation. In early 1980s was found that the avian erythroblastosis tumor virus was responsible for generating an abnormal form of the human epidermal growth factor receptor (EGFR). The retroviral gene (v-erb) responsible for avian erythroblastosis showed a high homology with c-erbB1. Also, in 1981 was identified that DNA obtained from rat neuroblastoma cell lines was able to induce transformation of mouse fibroblasts (1981, Nature) and the neu oncogene encoded a 185 kDa membrane-bound glycoprotein related to ErbB1. Amplification of the HER2 gene in cancer cells leads to overexpression of HER2 receptors on the cell surface, conducing to unbalanced signaling. In breast cancer, HER2 is gene amplified in 20%-25% of primary tumors and is associated with a more aggressive phenotype and poorer prognosis. HER2 is a type I transmembrane glycoprotein that contains an N-terminal extracellular domain (ECD), a single transmembrane helix, a TK domain, and an intracellular regulatory domain. ErbB3 has no kinase activity, ErbB2 has no direct ligand and in overexpressing ErbB2 tumors there are formed both heterodimers and homodimers. The list of partners interacting with ErbB proteins also includes integrins, which are heterodimers of an α and a β subunit. Several studies implied that integrins and growth factor receptors cooperate in tumor formation and demonstrated the existence of integrin-growth factor receptor complexes. Similar to ErbB2, integrins were shown to be raft-associated. Patients with ErbB2-overexpressing breast cancer are routinely treated with Herceptin/ Trastuzumab including drug regimens. Herceptin is the humanized version of an anti-ErbB2 mouse monoclonal antibody, 4D5, and is thought to lead to down-modulation of ErbB2 cell surface expression and inactivation of the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways. Taking advantage of studying hierarchical levels of molecular interactions using biophysical methods and correlate them with cellular and molecular responses to treatments against cell proliferation and metastasis will probably offer further significant advances in the future.

2. Tau and amyloid proteins in neurodegenerative diseases

3. Polyphenols in cancer research

B. DIRECȚII DE CERCETARE - CADRE DIDACTICE

1. Principalele aplicații ale citometriei în flux în cercetare și clinică