All human cells possess the same genome, yet their diverse identities and functionalities are determined by the intricate interplay of gene expression, epigenetic modifications, and chromatin structure. While each cell contains the complete set of genetic information, specific genes are selectively activated or silenced, leading to distinct cell types and specialized functions. This regulation is achieved through epigenetic modifications, such as DNA methylation and histone modifications, which act as "marks" on the DNA and associated proteins, influencing gene accessibility and expression. These epigenetic modifications create a complex regulatory landscape, allowing cells to respond to environmental cues and developmental signals.

Furthermore, maintaining the integrity of the genetic material is crucial for cellular function and viability. Cells are constantly exposed to various sources of DNA damage, including chemical insults, radiation, and errors during DNA replication. DNA damage repair mechanisms play a critical role in preserving the fidelity of the genome and preventing the accumulation of mutations. Cells employ intricate pathways and repair enzymes to detect and correct DNA lesions, ensuring the stability and functionality of the genetic material.

Additionally, the three-dimensional organization of chromatin within the nucleus plays a crucial role in cell fate determination and DNA damage repair. Chromatin architecture, including the positioning of nucleosomes, interaction between regulatory elements, and higher-order chromatin structures, contributes to the precise control of gene expression patterns and the accessibility of damaged DNA for repair machinery. Different cell types exhibit unique chromatin configurations that define their transcriptional profiles, functional characteristics, and capacity to respond to DNA damage.

By investigating the dynamic processes of gene expression, epigenetic modifications, chromatin structure, and DNA damage repair, we aim to unravel the mechanisms underlying cell identity, differentiation, and genome stability. Understanding how these factors interact and influence each other will provide valuable insights into the development, maintenance, and dysfunction of various cell types. Furthermore, this knowledge can offer potential therapeutic targets for diseases that involve aberrant gene expression, chromatin regulation, and DNA repair processes, such as cancer, neurological disorders, and aging. Our multidisciplinary research approaches, encompassing biophysical tools (NMR spectroscopy, Cryo-EM), molecular biology, protein chemistry, and sequencing techniques, allow us to delve into the intricate workings of these processes and contribute to advancing our understanding of cellular biology and its implications for human health.

Kim Lab at Case Western Reserve University

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