Associate Professor of Biological Sciences
Program Focus
Research in our group is focused on elucidating the molecular mechanisms of breast cancer cell cycle via proteomics and holistic, systems biology approaches. 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. Our 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. The mass spectrometry and proteomic technologies that we developed in our laboratory have enabled, so far, the identification of over 4000 breast cancer proteins, with representative protein clusters being mapped to all hallmarks of cancer. Differential protein expression analysis of the G1 and S cell cycle stages of breast cancer cells has revealed functional protein clusters that uncover new relationships between co-regulated protein networks with essential roles in transcription activation/repression, signaling and cell cycle control. Originators of proliferation, as possible drivers through the G1/S transition point in cancerous cell states, were found to be decisively abundant.
By providing novel insights into the functional categories that drive cancer cells into division, the data points to a broad range of potential therapeutic targets that concurrently affect the cell cycle signaling and transcriptional/translational machinery. The identified proteins can be used alone, or in combination, as target molecules for developing novel anti-cancer drugs and therapies, or as biomarker sets for cancer detection and diagnosis. We are pursuing the expansion of these projects with studies that will provide a better understanding of the functional implications of drug delivery and impact on signaling pathways that control cell proliferation.
Selected Publications
Tenga, M.J.; Lazar, I.M., “Proteomic Study Reveals a Functional Network of Cancer Markers in the G1-Stage of the Breast Cancer Cell Cycle,“ BMC Cancer 2014, 14, 710 (17 pages). DOI: 10.1186/1471-2407-14-710.
Yang, X.; Lazar, I.M., “XMAn: A Homo sapiens Mutated-Peptide Database for MS Analysis of Cancerous Cell States,” J. Proteome Res. 2014, 13(12), 5486-5495. DOI: 10.1021/pr5004467.
Tenga, M.J.; Lazar, I.M., “Proteomic Snapshot of Breast Cancer Cell Cycle: G1/S Transition Point,” Proteomics 2013, 13(1), 48-60. DOI: 10.1002/pmic.201200188.
Armenta, J.M.; Hoeschele, I.; Lazar, I.M., “Differential Protein Expression Analysis Using Stable Isotope Labeling and PQD Linear Ion Trap MS Technology,” J. Am. Soc. Mass Spectrom., 2009, 20, 1287-1302.DOI:10.1016/j.jasms.2009.02.029.
Yang, X.; Lazar, I.M., “MRM Screening and Biomarker Discovery: A Library of Human Cancer-Specific Peptides,” BMC Cancer 2009, 9(1), 96 (11 pages). DOI: 10.1186/1471-2407-9-96.