Deng Lab
Research Interests
Our general goal is to understand how environmental toxins influence development and health in molecular level. In particular, we are exploring the novel molecular mechanisms and biological functions of the Keap1-Nrf2 oxidative and xenobiotic response pathway in fruit fly (Drosophila melanogaster), using a combination of imaging, genetic, and molecular approaches.
Deng lab is also interested in developing fluorescence imaging tools to visualize protein complexes on chromatin, and using these methods to study protein interactions among transcription factors and chromatin modifiers at specific genomic loci.
Join Us
Deng lab is recruiting motivated scientists, including postdocs, graduates and undergraduates, to participate in our diverse research projects.
Please contact Dr. Deng (dengh@d.umn.edu) directly if you are interested in our lab.
Current Studies
1. Developmental functions of dKeap1-CncC
The Keap1-Nrf2 complex plays a central role in the oxidative and xenobiotic responses that protect cells from a variety of internal and external toxins. Nrf2 is a transcription factor that can bind to and activate a cassette of antioxidant and detoxifying genes. According to the established model, Keap1 interacts and inhibits Nrf2 in the cytoplasm in basal conditions. Mis-regulations of Keap1 and Nrf2 are associated with many diseases, including cancer, cardiovascular defects, chronic inflammation, neurodegeneration, and respiratory diseases. However, the pathological roles of Keap1 and Nrf2 are complicated, hindering the development of therapies targeting these proteins.
Recent studies have uncovered the roles of Keap1 and Nrf2 family proteins in regulating developmental genes and processes. Understanding the novel developmental functions of Keap1 and Nrf2 can offer new insights into their roles in human health. Using the Drosophila model, we're exploring the novel functions of dKeap1 and CncC in various developmental programs including adipogenesis, metamorphosis, and oogenesis. We have also demonstrated that dKeap1's chromatin-binding and transcriptional activity is mediated by its C-terminal domain.
Relevant publication:
Carlson et al. Drosophila Keap1 protein regulates developmental transcription through binding to chromatin. Developmental Biology 2022
Deng and Kerppola. Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation. Development 2014
Deng. Multiple roles of Nrf2-Keap1 signaling: Regulation of development and xenobiotic response using distinct mechanisms. Fly 2014
Deng and Kerppola. Regulation of Drosophila metamorphosis by xenobiotic response regulators. PLoS Genetics 2013
2. Epigenetic functions of dKeap1-CncC
Our preliminary studies suggest a potential role for dKeap1-CncC in regulating the structure of Drosophila polytene chromosomes. To gain a comprehensive understanding of the epigenetic functions of Keap1-Nrf2 family proteins, we are currently employing imaging and genetic tools to investigate how dKeap1 and CncC influence chromatin architecture and gene expression, both globally and at specific genomic loci. Additionally, we are exploring the molecular and genetic interactions between the dKeap1-CncC complex and various chromatin modifiers, including lamin.
Our hypothesis is that the dKeap1-CncC xenobiotic response signaling pathway mediates the modulation of the epigenome and development in response to environmental toxins.
Relevant publication:
Carlson et al. Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture. Molecular Biology Reports 2024
Carlson et al. Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors. Genesis 2019
3. Imaging protein complexes on chromatin
The Biomolecular Fluorescence Complementation (BiFC) assay is a powerful tool for visualizing protein interactions within living cells. In this assay, fluorescent protein fragments are fused to interacting protein partners, and the formation of protein complexes is indicated by the resulting fluorescence. We have successfully introduced the BiFC assay into Drosophila, allowing us to visualize protein interactions in various tissues. By adapting the BiFC assay for use with polytene chromosomes, we have developed a novel imaging technique that for the first time enables direct visualization of protein complexes at specific genomic loci. This method can be applied to identify genes specifically targeted by a protein complex.
We are currently using the polytene chromosome BiFC assay to investigate the formation of multiple protein complexes at specific chromatic loci and to study how xenobiotic stimuli influence the binding specificities of these complexes on chromatin.
Relevant publication:
Neidviecky and Deng. Determination of complex formation between Drosophila Nrf2 and GATA4 factors at selective chromatin loci demonstrates transcription coactivation. Cells 2023
Deng and Kerppola. Visualization of the genomic loci that are bound by specific multiprotein complexes by bimolecular fluorescence complementation (BiFC) analysis on Drosophila polytene chromosomes. Methods in Enzymology 2017
Deng and Kerppola. Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation. Development 2014