RESEARCH

Discover what we're discovering
We're passionate about many questions. How do various dynamic epigenetic changes in chromatin structure impact gene expression during stem cell pluripotency/self-renewal, cellular differentiation, and reprogramming? How does three-dimensional chromosomal structure and disregulation contribute to development of diseases such as aging and cancer? The long-term goal of the Wang Lab is to translate our understanding of these complex mechanisms to studies of human diseases.

Stem cell
pluripotency
and self-renewal

ROyal jelly for royal bees...

Significant phenotypic differences exist between queens and worker honey bees, yet both develop from identical larvae. What drives their developmental differences is the amount of Royal Jelly fed to the larvae: all larvae receive these nutrients, however, the selected larvae to become queens are fed far larger quantities. The active component of Royal Jelly, called Royalactin, has regenerative effects in mammals and can impact longevity and fertility across different species. In studying the effects and biology of Royalactin, we discovered its mammalian structural analog, Regina. Studies on the current method of culturing mouse embryonic stem cells have shown the deleterious effects of long-term cultured ES cells in a group of inhibitors that target MAPK/ERK Kinase (Mek) and glycogen synthase kinase-3 (GSK3), in conjunction with Leukemia inhibitory factor (LIF). Prolonged suppression of these pathways limit the cells’ developmental potential, rendering them ineffective for long-term applications. Using Royalactin and Regina, we have successfully maintained long-term stem cell pluripotency without compromising genetic integrity and renewed the ES cells to an earlier embryonic state. We are actively working on completing our understanding of the biology of these proteins and other applications for their use.

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Notable Publications

HONEY BEE ROYALACTIN UNLOCKS CONSERVED PLURIPOTENCY PATHWAY IN MAMMALS
Fanucchi et al., Nature Communications, 2018

THE PHENOTYPIC EFFECTS OF ROYAL JELLY ON WILD-TYPE D. MELANOGASTER ARE STRAIN-SPECIFIC
Morgan et al., PLoS Genetics, 2016

dynamic chromosomal architecture

Cloud nine?

The distinct shape in which our genome is organized can determine and play a significant role in gene expression. How chromatin folds on itself naturally and abnormally is particularly important in the contexts of cancer and development. We created CLOuD9, a unique tool that allows for selective and reversible modification of chromatin loops. Using this tool, we can create artificial loops, reverse de novo loops, and study their effects on gene expression.

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Notable Publications

CRISPR-MEDIATED REORGANIZATION OF CHROMATIN LOOP STRUCTURE
Morgan et al., Journal of Vis Experiments, 2018

MANIPULATION OF NUCLEAR ARCHITECTURE THROUGH CRISPR-MEDIATED CHROMOSOMAL LOOPING
Morgan et al., Nature Communications, 2017

LONG NONCODING RNAS

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LONG NONCODING RNAS

Long noncoding RNAs have been recognized as an important gene regulation mechanism, and have been observed acting on a transcriptional, RNA processing, translational, and post‐translational level. We are currently investigating an saRNA-mediated RNA-activation mechanism that upregulates lncRNAs targeting important TH2 cytokines.

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Notable Publications

IMMUNE GENES ARE PRIMED FOR ROBUST TRANSCRIPTION BY PROXIMAL LONG NONCODING RNAS LOCATED IN NUCLEAR COMPARTMENTS
Fanucchi et al., Nature Genetics, 2019

NONCODING RNAS IN WOUND HEALING: A NEW AND VAST FRONTIER
Luan et al., Advances in Wound Care, 2018

PICSAR: LONG NONCODING RNA IN CUTANEOUS SQUAMOUS CELL CARCINOMA
Luo et al., Journal of Investigative Dermatology, 2016