The Laboratory of Chromatin
Biology and Cancer Epigenetics

Research

The human genome is estimated to contain approximately 20,000 protein-coding genes, all within a staggering total of 3,200 megabases of DNA. Perhaps even more astonishing is the complex network of factors encoded by the DNA that act in the cell to precisely control its own accessibility and expression, while enabling flexibility to respond to external stimuli. In the cell, the DNA exists wrapped around histone protein complexes, forming a structure known as chromatin. Chromatin provides the dynamic platform for which transcription can be regulated in a spatiotemporal manner. Fundamentally, the field of chromatin biology represents an investigation into this intricate function of DNA, the molecules that interact with it, and how these associations facilitate underlying cellular processes necessary for life.

 

Paramount to precisely controlling gene expression is the selective deposition of biochemical modifications, such as cytosine methylations or post-translational modifications (PTMs) of amino acid residues in histones. These epigenetic alterations are installed and manipulated by a range of chromatin-modifying and remodeling enzymes, which collectively dictate transcriptional output and coordinate specific molecular programs within a given cell. In addition to the vital role of chromatin regulators in normal biology, mutations can drive chromatin dysregulation, leading to cancer. It is an active goal of the chromatin biology field to understand how these chromatin-modifying and remodeling enzymes operate and influence phenotypes and the mechanistic principles underlying how they are able to regulate with exquisite specificity.

 

 

The Soto-Feliciano lab seeks to investigate this landscape of chromatin-modifying and epigenetic factors to understand how they operate in normal physiology and disease, notably in leukemias and pediatric cancers, where genetic abnormalities in chromatin regulators are common. Uniquely, our research program focuses on the roles of an underappreciated class of chromatin regulators that serve as adaptors or scaffolds for other chromatin-modifying complexes, which we hypothesize may function as a central link for transcriptional control and specificity. Utilizing and developing a wide array of experimental tools and models, we aim to discover new paradigms of chromatin biology that will enrich our understanding of gene expression and lead to novel treatment strategies. Guided by a deep scientific curiosity and adherence to data reproducibility and rigor, the Soto-Feliciano lab is eager to collaborate with biologists, engineers, and clinicians alike to illuminate the mysteries of chromatin biology!

 

Please consider supporting our work or joining our team as a new member. For inquiries, please contact us.

 

Locus-specific targeting and gene regulation by chromatin adaptors

We study how chromatin adaptor/scaffold proteins achieve precise targeting of molecular machinery to specific genomic loci to regulate transcription. We aim to uncover the mechanisms by which these adaptors recognize and bind to particular histone modifications and DNA sequences and interact with transcription factors, guiding the assembly of multiprotein complexes that control gene expression. By integrating advanced genetic and multi-omic approaches with cutting-edge epigenetic techniques, including CUT&RUN, we seek to elucidate the critical roles of chromatin adaptors in gene regulation, with a focus on their implications in cancer and other diseases.

Context-specific nature of chromatin regulators in development and disease

We explore the role of adaptors/scaffolds in chromatin interactions and gene regulation. Using innovative techniques such as CRISPR-based genome targeting (dCas9-Adaptor fusions), proximity labeling (CASPEX), and quantitative proteomics, we map the interaction networks of chromatin adaptors and identify their key effectors. By integrating genetic, biochemical, cell and molecular biology, and epigenomics and structural biology approaches, we seek to uncover the molecular mechanisms underlying the context-specific functions of chromatin adaptors in cancer and other human disorders.

Disease-associated mutations in chromatin and epigenetic regulators

Our research is also dedicated to uncovering how aberrant chromatin and epigenetic mechanisms contribute to cancer and developmental disorders. We study how mutations in chromatin and epigenetic regulators disrupt the normal functions of tumor suppressor genes, activate oncogenes, and lead to abnormal cell fate transitions. Through a combination of CRISPR screens, saturation mutagenesis, advanced in vitro and in vivo models, and cutting-edge transcriptomics and epigenomics tools, we aim to unravel the biological impact of these mutations.

Locus-specific targeting and gene regulation by chromatin adaptors

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Context-specific nature of chromatin regulators in development and disease

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Disease-associated mutations in chromatin and epigenetic regulators

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We study how chromatin adaptor/scaffold proteins achieve precise targeting of molecular machinery to specific genomic loci to regulate transcription. We aim to uncover the mechanisms by which these adaptors recognize and bind to particular histone modifications and DNA sequences and interact with transcription factors, guiding the assembly of multiprotein complexes that control gene expression. By integrating advanced genetic and multi-omic approaches with cutting-edge epigenetic techniques, including CUT&RUN, we seek to elucidate the critical roles of chromatin adaptors in gene regulation, with a focus on their implications in cancer and other diseases.

We explore the role of adaptors/scaffolds in chromatin interactions and gene regulation. Using innovative techniques such as CRISPR-based genome targeting (dCas9-Adaptor fusions), proximity labeling (CASPEX), and quantitative proteomics, we map the interaction networks of chromatin adaptors and identify their key effectors. By integrating genetic, biochemical, cell and molecular biology, and epigenomics and structural biology approaches, we seek to uncover the molecular mechanisms underlying the context-specific functions of chromatin adaptors in cancer and other human disorders.

Our research is also dedicated to uncovering how aberrant chromatin and epigenetic mechanisms contribute to cancer and developmental disorders. We study how mutations in chromatin and epigenetic regulators disrupt the normal functions of tumor suppressor genes, activate oncogenes, and lead to abnormal cell fate transitions. Through a combination of CRISPR screens, saturation mutagenesis, advanced in vitro and in vivo models, and cutting-edge transcriptomics and epigenomics tools, we aim to unravel the biological impact of these mutations.

Please consider supporting our work or joining our team as a new member.
For inquiries, please contact us.

Funders