Research

Research in the Taube Lab focuses on cancer stem cells, epithelial-mesenchymal plasticity and their roles in breast cancer metastasis. Current lab projects are exploring regulators of chromatin accessibility, microRNAs, and drug-like natural products.

Also, check out our publications!

MicroRNA-203 Reverses EMT and Blocks Metastasis

MicroRNAs are small non-coding RNAs, transcribed from the genome, which have the capacity to regulate hundreds of other transcripts by base-pair binding of a 21 nucleotide sequence to a matching sequence on their target. We have demonstrated that microRNA-203 (miR-203) is strongly repressed by EMT. Re-expression of this microRNA in cells which have undergone EMT reverts them to an epithelial phenotpye, decreases their migratory capacity and prevents metastasis (Taube et al. 2013). We are working to characterize the downstream effectors regulated by miR-203 and the potential utility of elevating miR-203 expression in primary tumors.

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Regulators of Histone Methylation Facilitate EMT Reversal

Histones are proteins which facilitate the condensation of DNA in the nucleus. Tight regulation of the accessibility of the DNA is essential for appropriate gene expression. One mechanism underlying this is the post-translational modification of histones, termed the histone code. We have demonstrated that EMT drives genome-wide changes in the histone methylation landscape and that these changes underlie the changes in expression of thousands of genes (Malouf and Taube et al. 2013) and that a histone demethylase is responsible for remodeling bivalency across the genome in cancer stem cells (Taube and Sphyris et al. 2017). We are working to characterize the specific roles of proteins which ‘write’ the histone code, proteins which ‘read’ the histone code, and proteins that ‘erase’ the histone code in epithelial-mesenchymal plasticity.

Funded by Susan G. Komen #CCR18548469

Collaborators

Dr. Michael Lewis, Baylor College of Medicine

Josh Newby, Patient Advocate

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EMT-driven cancer stem cell sensitization to small molecules

Cancer stem cells act as highly-adaptable tumor-initiating cells, which colonize tumor growth in secondary metastatic sites. CSCs may arise naturally from dedifferentiated adult cells, yet, in tumors, the epithelial-to-mesenchymal transition (EMT) has been shown to yield CSCs. It may be through this de-differentiation transition that cancer cells gain their stemness, making EMT an attractive process to target in the attempts to eliminate CSCs. Our work seeks to understand the EMT-associated mechanisms responsible for sensitization to a fungus-derived natural product, driving further insights into the effect of small-molecule inhibition of EMT/CSC-driven phenotypes in reducing chemoresistance in TNBC metastases.

Funded by CPRIT #RP180771

Collaborators

Dr. Daniel Romo, (Baylor, Dept. of Chemistry)

 

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Defining the relationship between bacterial outer membrane vesicles and the biology of colonic epithelia and cancer stem cells

Microbiota shed vesicles containing number biomolecules. These molecules have the potential to modulate the biology of the host epithelium or immune system, potentially affecting homeostasis and cancer progression.

Collaborators

Dr. Leigh Greathouse (Baylor, Dept. of Nutritional Science), webpage

 

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MiniPharma Collaboration

The MiniPharma group is an undergraduate-lead collaboration under the guidance of Drs. Romo (synthetic chemistry), Schuford (computational chemistry), and Taube (cancer biology) and graduate students.

The goal of the collaboration is to provide participating undergraduates with a ‘taste’ of the pharmaceutical industry with respect to development of small molecule inhibitors as potential chemotherapeutics by focusing on early stage drug lead development for cancer treatment.

See the website for more information or to get involved!

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