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.
One of the goals of HSS is to advance the science of orthopedic surgery, rheumatology, and related disciplines for the benefit of patients. Research staff at HSS may collaborate with outside companies for education, research and medical advances. HSS supports this collaboration in order to foster medical breakthroughs; however, HSS also believes that these collaborations must be disclosed.
As part of the disclosure process, this website lists Research staff collaborations with outside companies if the Research staff member received any payment during the prior year or expects to receive any payment in the next year. The disclosures are based on information provided by the Research staff and other sources and are updated regularly. Current ownership interests and leadership positions are also listed. Further information may be available on individual company websites.
As of July 24, 2018, Dr. Chinenov reported no financial interest relationships with healthcare industry.
By disclosing the collaborations of HSS Research staff with industry on this website, HSS and its Research staff make this information available to patients and the public, thus creating a transparent environment for those who are interested in this information. Further, HSS’ Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.