Chromatin and Regulation of Gene Expression

Research includes:

  • Biochemistry
  • Chromatin
  • DNA Repair
  • Gene Expression
  • Genomics
  • Nucleic Acids
  • Transcription

Training Group Mission:

Students in this training group work with a diverse group of faculty who employ an extensive range of experimental approaches with the goal of understanding chromatin and regulation of eukaryotic gene expression. Recent advances in the identification of chromatin modifying proteins and in the elaboration of the “histone code hypothesis” illustrate the value of interdisciplinary approaches in gaining insights into this exciting area of research. Students also have the opportunity to examine the effect of chromatin on other DNA-based processes such as replication, recombination, and repair. All students receive broad training in genetic, biochemical, and genome-based approaches in analysis of these fundamental processes.


Faculty Membership

Faculty
Research Area
The role of protein phosphatases in regulating cellular plasticity and therapeutic resistance in cancer
Role of histone methylation in gene expression and oncogenesis
Transcriptional regulation in poxviruses
Structure and function of large protein complexes; Cryo-electron microscopy.
The genetic basis of reproductive barriers and molecular mechanisms of plant adaptation. Cost effective integration of genomics for comparative and forward genetics research approaches.
Our major goal is to understand how the misregulation of chromatin leads to cancer progression. A major focus for the lab is on chromatin targeting subunits of chromatin remodeling complexes, in particular the heterogeneous collection of SWI/SNF chromatin remodeling complexes. We have determined that Polybromo 1 (PBRM1), a chromatin targeting subunit of the PBAF subcomplex, is important for the transcription of stress response genes in renal cancer, and that BRD9, a chromatin targeting subunit of the recently characterized GBAF (or ncBAF) subcomplex, is required for androgen receptor signaling in prostate cancer. Another focus of the lab is on the CBX chromatin targeting subunit of Polycomb repressive complex 1, which is represented by five CBX paralogs in mammals. We have made significant progress in establishing glioblastoma's dependence on CBX8 expression for viability, defining downstream targets of CBX8, and defining the contribution of the chromodomain to CBX8 targeting. Our current goal is to use our recently developed CBX8 inhibitors in combination with biochemical and proteomic approaches to connect paralog-specific biochemical function for CBX8 to a paralog-specific role in glioblastoma.
Genetic and genomic investigation of naturally-occurring canine diseases and traits
Regulation of mineral metabolism, molecular actions of vitamin D in calcium metabolism and cancer prevention, gene-environment interactions influencing bone/calcium metabolism or cancer
Mechanism of the transfer to and expression of the Agrobacterium tumefaciens Ti-plasmid in plant cells
Regulation of gene expression by epigenetic mechanisms has emerged as a fundamental process that controls mammalian development and normal function. Epigenetic mechanism constitutes DNA methylation, post translational modification of histone tails, chromatin conformation and non-coding RNA. The histone tail modifications and DNA methylation are established and maintained by various enzymes which include methyltransferases. The expression and activity of these enzymes particularly the DNA methyltransferases (DNMTs) is subjected to a tight regulation during development and in somatic cells. Research in Gowher lab is largely focused on unravelling mechanism/s that regulate the expression and activity of the mammalian DNA methyltransferases during development and in diseased state. Dr. Gowher has published 37 peer-reviewed publications in the field of epigenetics. Most of her work has focused on questions related to DNA methylation, including the specificity of Dnmts, their distinct functions, and interactions with other epigenetic regulators. All these studies are performed using innovative biochemistry and molecular biology techniques, which include high throughput Bisulphite-sequencing (Bis-SEQ), Chromatin Immunoprecipitation-sequencing (ChIP-SEQ), RNA-SEQ and Mass Spectrometry. The lab is currently funded for four major projects. 1) Regulation of enhancer activity by cross talk of chromatin modifiers and Dmt3A and 3B; 2) Role of chromatin configuration (enhancer-promoter interactions) in regulation of DNMT3A and DNMT3B activity; 3) Mechanism by which Vezf1 regulates gene expression during endothelial differentiation and angiogenesis; 4) co-regulation of DNMT3B transcription and alternative splicing by its upstream enhancer and non-coding RNA.
We study the initiation, progression, and metastasis of vascular sarcomas with a focus on the role of microRNAs.
The Hu lab has developed an integrated research program that involves technology development, basic biological research, and clinical translation. The lab uses multiple approaches (including biochemical, structural, molecular, cellular, imaging, genetic, mice studies, 'omics', clinical patient analysis, and bioinformatics) to study several aspects of cancer. The lab focuses on clinically relevant problems and studies cancer development, progression, and mechanisms of treatment resistance. Current research in the lab is focused on the epigenetic role of protein arginine methyltransferase 5 (PRMT5) in reprogramming therapy-induced neuroendocrine differentiation in prostate, lung and pancreatic cancers and the development of novel therapeutics for cancer treatment.
Biological roles of miRNAs and their use as cancer therapeutics
Epigenetics, Impacts of Chromatin on Gene Expression, DNA Replication & DNA Repair
Gene expression during mammalian development; cancer model systems
The Konradt lab studies infections and the subsequent host immune response in two separate, yet overlapping compartments: the vascular system and the placenta.
Understanding how the cell nucleus directs expression and stability of the genome and how tissue architecture influences nuclear organization; development of 3D cell culture and organ-on-a-chip models for discovery of targets and cell nucleus-based readouts in cancer prevention and treatment;
Epigenetic regulation of transposable elements
Functional genomics; Epigenomics; Histone modification; Environmental responses; Systems Biology; Plant Genetics
Regulation of cell identity, signal transduction, chromatin remodeling
Oncogene expression in eukaryotic cells
Defining the Molecular Basis for p68 (Dbp2) in Gene Expression and Cellular Proliferation

Aging photoreceptors in the eye show characteristic changes in gene expression. Our lab is interested in understanding the mechanisms that drive these changes in gene expression. These studies provide a model for understanding how aging contributes to ocular diseases such as age-related macular degeneration. Our work is funded by the National Eye Institute of the NIH. We are actively seeking new graduate students, so please contact us if you are interested in joining our group.

Maize genetics, genomics, value-added traits
Signal transduction in cancer biology, early neuronal development and cancer metabolism.
1. Structures and functions of DNA G-quadruplex secondary structures. We seek to understand the molecular structures and cellular functions of the biologically relevant DNA G-quadruplexes, including those formed in the promoter regions of human oncogenes such as MYC, BCL-2, and PDGFR-b, as well as in human telomeres. 2. Protein interactions of G-quadruplexes. We work to understand the structures and cellular functions of proteins that interact with DNA G-quadruplexes, and their therapeutic targeting. 3. Targeting G-quadruplexes for anticancer drug development. DNA G-quadruplexes are emerging as a new class of cancer-specific molecular targets. We seek to discover small molecular anticancer drugs that target the DNA G-quadruplexes for oncogene suppression (e.g. MYC). We hope to combine the potency of DNA-interactive anticancer drugs with the selectivity properties of molecular-targeted approaches. 4. Structure-based rational drug design. We use structure-based rational design in combination with structural biology, biophysical, biochemical, and cellular methods for our drug development efforts. 5. Topoisomerases’ and transcription factors’ inhibitors.

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