All cells in our body have identical genes. During our fetal development, cells specialize by turning on some genes and blocking or reducing activity of others. Thus, we become a complex organism with different specialized cells in different tissues. The activity of different genes in different cells is further fine-tuned from our birth to our death, in response to organismal needs and external stressors. My research is focused on understanding how our genes are turned on and off as an adaptation to changing cellular environment in health and disease.
Out of thousands of genes in human cells only a fraction are active at any given time. The set of active genes defines the cell type. The gene activity profile of a cell often changes in disease. Detecting such changes (gene expression profiling) allows us to detect many diseases at early stages and offer an early intervention or a monitoring program. Gene activity is controlled by regulatory elements in a genome. Proteins that bind to these elements (transcription factors) are ultimately responsible for turning genes on and off. Transcription factors are often altered in disease and could be used as disease indicators or drug targets.
Inflammatory reaction triggers changes in expression of hundreds of genes and profoundly alters cellular physiology. These changes are often short-lived and revert to “normal” after the inflammation is resolved. When inflammation is prolonged or becomes chronic, the expression of inflammation-related genes persists, causing permanent debilitating changes in cells and tissues, often seen in patients with rheumatoid arthritis, lupus, multiple sclerosis, and other inflammatory disorders. Understanding correlations between specific changes in gene activity profile and manifestations of a particular disease is essential for correct diagnosis and selection of optimal treatment. We use next-generation sequencing technologies, such as RNA-seq, to track the activity pattern of all genes in affected cells, in order to identify sets of genes related to a specific inflammatory disorder.
Gene activity is controlled by the joint action of multiple regulatory agents, known as transcription factors, that interact with DNA and other proteins. The repertoire and activity of transcription factors in a given cells is ultimately responsible for its unique pattern of gene activity. Many transcription factors are engaged in shaping inflammatory response. The exact genes regulated by specific transcription factors, however, remain unknown. We use high-throughput whole genomics approaches, such as Chip-seq and ATAC-seq, to determine the specific location of regulatory elements in a genome and match it to the known genomic features – genes, sequence variants, and other regulatory elements. Our ultimate goal is to construct a disease-specific network of transcription factors and their targets to pinpoint specific biological pathways that are either responsible for disease manifestation or serve as diagnostic markers.
Bioinformatics Scientist, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery
For more publications, please see the PubMed listing.
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As of May 31, 2023, Dr. Chinenov reported no relationships with healthcare industry.
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