Medical Institute of Bioregulation, Kyushu University

Title

Deciphering transcriptional mechanisms to drug them: a path from development to rare diseases

Speaker

Mathias Francois, Ph.D.
Professor
University of Sydney School of Medical Science and The Centenary Institute

Date

Mar. 6 (Wed), 2024
17：00〜18：00

Venue

Seminar Room 105, 1F, Biomedical Research Station, Hospital Campus
No.34 on the map.

Abstract

Despite a growing catalogue of secreted factors critical for tissue assembly during organogenesis, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells . Recent work from the laboratory has uncovered multiple roles for endothelial cells as tissue organiser which coordinate the growth and morphogenic process of the lymphatic vascular network and cardiac tissue. In this talk, I will highlight the importance of an endothelial specific transcription factor that coordinates paracrine signalling and cell to cell interactions to instruct cardiac tissue formation. Our findings reveal that the endothelium has the potential to contribute to the aetiology of left ventricular non compaction and offer new research directions to improve the early detection of this heart disease.
Further, I will show a novel molecular strategy that is efficient to interfere with transcription factors activity to perturb vascular outgrowth in pre-clinical model systems. Using this new strategy we have identified FDA-approved drugs that has been successfully repurposed to manage two rare vascular disorders in human and infantile hemangiomas. Our work provides a proof of therapeutic utility for a novel strategy to inhibit transcription factor activity, re-establishing transcription factors as a viable class of molecular targets for small molecules in therapeutic settings.

References

1. E.S. Wong et al.
   Deep conservation of the enhancer regulatory code in animals. Science , 2022.
2. C.T. Seebauer et al.
   Non–beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma. J. Clin. Invest. , 2022.
3. I.K.N. Chiang et al.
   The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner. EMBO J. , 2023.

Contact

Division of Gene Expression Dynamics,
Medical Research Center for High Depth Omics,
Medical Institute of Bioregulation
Hiroshi Ochiai
TEL: 092 (642) 6882