Dr. Lazar's research is focused on elucidating the molecular mechanisms of breast cancer cell cycle via proteomics and systems biology approaches. Her lab is using and developing advanced mass spectrometry and micro/nano-fluidic technologies that enable a detailed interrogation of biological systems.
Cancer is a disease of the cell cycle that results in uncontrolled proliferation of cells. The great majority of breast cancers (~70 %) express estrogen receptors (ER) in the cell, mainly in the nucleus, but also in the cytoplasm and plasma membrane. About 20-25% of invasive breast cancers display an amplification of the human epidermal growth factor receptor (HER2) gene and/or ovexpression of HER2 cell surface tyrosine kinase receptors, increasing metastatic potential and decreasing survival rates. Most cancers exhibit some, if not all, of eight major characteristics: cancer cells evade apoptosis, are able to proliferate in the absence of growth factors, ignore inhibitory factors, recruit their own blood supply, avoid immune destruction, display deregulated cell energetics, become immortal and are able to metastasize. Dr. Lazar's laboratory is using ER+ and HER2+ breast cancer cells to investigate the molecular mechanisms that enable cancer cells to bypass tightly regulated molecular checkpoints such as the G1/S restriction point, proliferate in an unrestrained manner, metastasize and hijack normal biological function. Holistic, systems biology approaches based on mass spectrometry and proteomic technologies that have been developed in Lazar's laboratory have led so far to the identification of over 4000 breast cancer proteins, with representative protein clusters being mapped to all hallmarks of cancer. The development of microfluidic technologies have enabled the identification of putative biomarker panels from only a few µg of cell extract. The availability of a priori knowledge regarding the co-expression of relevant cell-cycle control and check-point proteins, growth factor receptors, signal transduction proteins, transcription factors, DNA repair proteins, proteins involved in angiogenesis and metastasis, and proteins that promote apoptosis, will help elucidate the mechanisms of cancer cell proliferation and of molecular cross-talk between various signaling pathways, and will facilitate future studies that aim at the discovery of new biomarkers and drug targets.