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Projects

Sempere Laboratory

microRNA RESEARCH PROGRAM

Work in the Sempere Laboratory on various cancer associated-microRNAs is multi-disciplinary and includes:

  • Molecular biology and cellular biology studies to identify microRNA functions and targets
  • Genetic engineering of pre-clinical models to assess microRNA’s role within specific cellular compartments of tumor microenvironment
  • Molecular pathology with innovative human tissue-based multiplex ISH/IHC assays to implement diagnostics applications of microRNA biomarkers in a in clinical setting
  • State-of-the-art core resource services and the expertise of other Van Andel Research Institute faculty also facilitate several investigative areas. Some of these collaborative efforts integrate microRNA knowledge with that of other gene classes, while others build on new technologies developed for microRNA studies.

MOLECULAR PATHOLOGY STUDIES

Tissue samples are the direct connection between cancer research and cancer medicine. Detailed cellular and molecular characterization of tumors presents a unique opportunity to translate scientific knowledge into actionable clinical information. The Sempere lab has implemented multiplex assays for co-detection of microRNA and protein markers using a U.S. Food and Drug Administration-approved automated staining station in a College of American Pathologists-accredited environment. These assays combine the capabilities of gene expression signatures (multiple marker detection) and tissue slide (cell type-specific contextual information) analyses. The Sempere lab plans to establish a fully automated pipeline from multiplex marker detection to computer-assisted image analysis. This technology will enable the lab and collaborators to assess tissue heterogeneity and the tumor microenvironment and to generate clinically-relevant information.


 
MECHANISTIC STUDIES

A more detailed molecular understanding of microRNA-mediated processes in cancer is needed. Pre-clinical models provide an excellent system to address these mechanistic questions and optimize the efficacy and targeted delivery of microRNA activity modulator compounds. The Sempere lab uses complementary genetic engineering (e.g., Cre/LoxP and CRISPR/Cas systems) and synthetic compound approaches to investigate the role of specific microRNAs within specific compartments of the tumor microenvironment. The lab also assesses the contribution of these microRNAs to apoptotic and metastatic programs, and their ability to protect cancer cells against current cytotoxic and/or targeted therapies.

Figure 4. Predominant upregulation of miR-21 expression within reactive stroma in mammary tumor of PyMT-driven breast cancer model.

 

COLLABORATIVE TRANSLATIONAL RESEARCH PROJECTS AND INTERACTIONS

Several lines of investigation in the Sempere Laboratory are facilitated by state-of-the art core resource services (Jewell) and expertise of other Van Andel Research Institute faculty on focused areas of common scientific interest. Some of these collaborative efforts integrate microRNA knowledge with that of other gene classes, including tissue-based diagnostic applications that combine informative power of microRNA and glycan expression in pancreatic cancer (Haab Laboratory). Other collaborative efforts build on new technologies developed for microRNA studies, but that have broader applications for biomarker discovery and contextual characterization of tumor lesions, including identification of immune cell responses and checkpoint regulators.

Key:

  • High-content ISH/IHCplexing
  • Stromal signatures in TNBC
  • Dissecting cell type-specific activity of miR-21

  • Enodometriosis:
    Characterization of hormonal

    and immune responses, and
    stromal composition   

     

  • miRNA/glycome diagnostics
  • Stromal miR-21 interactions
  • PDAC PDX models
  • miR-155 immunotherapy reprogramming