Abstract

Many years and billions spent for research has not yet produced an effective answer to cancer. Not only each human, but even each cancer nodule in the same tumor, has unique transcriptome topology. The differences go beyond the expression level to the expression control and networking of individual genes. Moreover, the transcriptome topology has random dynamics due to the stochastic fluctuations of the microenvironment and external stimuli. The unrepeatable heterogeneous transcriptomic organization among humans makes senseless the meta-analysis of large populations and the quest for universal biomarkers and “fit-for-all” treatments. We present a bioinformatics procedure to identify for each patient his/her unique triplet of cancer Gene Master Regulators (GMRs) and predict consequences of their experimental manipulation from high throughput gene expression profiles. The procedure is based on the Genomic Fabric Paradigm (GFP), which characterizes each individual gene by the independent expression level, variability and coordination with each other gene, a four order of magnitude increase of the information provided by the transcriptomic experiments. GFP can identify the GMRs whose controlled alteration would selectively kill the cancer cells with little consequence on the normal tissue. So far, the method was applied to microarray data generated in the IacobasLab by profiling surgically removed prostates, kidneys and thyroids from people with metastatic cancers, and standard cell cultures of human cancers of prostate, thyroid, lung and blood. The applications verified that each cancer case is unique and predicted the consequences of the GMRs’ manipulation. The experiments were performed in the academic laboratories of former trainees from: Australia, Brazil, Georgia, Israel, New Jersey, New York, Romania and Texas.

Speaker Bio

Dr. Dumitru A. Iacobas, Research Professor and Director of the CCSB Personalized Genomics Laboratory since 2018, is an expert of both experimental and computational genomics. Trained as a biophysicist (PhD of the University of Bucharest, Romania), he was on faculty positions at medical schools from Romania (1981-2001) and NY (Albert Einstein College of Medicine-Neuroscience 2001-2013, New York Medical College-Pathology 2013-2017). At NYMC he founded and directed the Systems Biology Core and at Einstein he was the Associate Director of the Neurogenomics and Biometry Core Facilities. Of the 323 Iacobas’ publications (3 patents, 37 books/editions, 21 book chapters, 105 articles, 27 conference proceedings, 86 genomic dbases, 2 bioprotocols, 7 bioprojects, 7 nucleotides, 24 proteins etc.) 74 are as single author, 157 as first author and 32 as last (senior) author. The cancer-related publications include 3 book chapters and 10 papers in: Biological Theory, Cancers, Cancer and Oncology Research, Cells, Current Issues in Molecular Biology, Genes, J Cancer Immunology, Oncotarget, and World J Clinical Oncology. Moreover, he is the Guest Editor of the MDPI Special Issue “Molecules at Play in Cancer” https://www.mdpi.com/journal/cimb/special_issues/molecules_cancer (12 articles so far).