Our Research

"Engineering the tunable biochemical mechanisms of centrosomes and cilia biogenesis and targeting them in engineered 3D human tissues for clinical application."

We are a group of scientists interested in understanding the basic principles of centrosomes and cilia biogenesis. These are critical organelles of life. We engineer centrosome and ciliary biomolecules and thus study their functions in the delicate balance between neural stem cell homeostasis and tumorigenesis.

OUR OVERARCHING QUESTIONS

1. How does the human brain develop and degenerate? Can we study these using human brain organoids?
2. How do centrosomes and cilia play a role in these processes? Can we target these structures for potential therapeutic use?

OUR RESEARCH

Our research focuses on dissecting how centrosomes and cilia function as molecular switches that determine the homeostatic control of neural stem cells. We have identified principles of centrosome and cilia biogenesis over the last decade, using powerful Drosophila genetics combined with genetic engineering and biochemistry.

We now wish to understand how these structures critically regulate the functions of neural stem cells in human brain development and degeneration. To this end, we first bioengineer stem cells to generate self-assembling 3D brain-like tissues, such as brain organoids. We use these tissue-engineered brain organoids as a model system to decipher general rules of cilia's role as a molecular switch in brain development, cell physiology, neurodegeneration, and tumorigenesis, with a particular emphasis on translating basic research into the identification of molecular targets for human diseases.

To address these, we develop and apply advanced molecular engineering, super-resolution imaging tools, including 3D SIM and STED microscopy, complemented by high-content live imaging, light-sheet, electron microscopy, multi-omics, machine learning, and computational biology (see our infrastructure section)

IMPACT

Our research focused on engineering biomolecules, stem cells, and tissues to uncover previously unknown mechanisms of neural stem cell maintenance in human brain development and tumorigenesis. The application of basic biology and brain organoid systems will model human brain disorders and apply drug discovery programs for human diseases.

BROAD AREAS OF INTEREST

RESEARCH THEME 1: Next generation brain organoids (see our brain organoid innovation unit and biobank)

• Stem cell and tissue engineering of human brain organoids
• Development of next-generation organoid culturing technologies
• Personalized human brain organoids to model microcephaly and other monogenic mutations causing defective brain development
• Dissecting the mechanisms of emerging neurotropic viruses affecting the human brain

RESEARCH THEME 2: Centrosomes and primary cilia in brain tissue organization

• Mechanisms and discovery of new molecules of centrosome and primary cilium biogenesis
• Cilium dynamics (Cilium checkpoint) regulating neural stem cell maintenance in tissue organization
• Targeting centrosomes and cilia-mediated cellular mechanisms using therapeutic standard small molecules

RESEARCH THEME 3: Patient-specific brain organoids to model rare neurogenetic diseases

• Recruiting patients harboring monogenic mutations and variants of unknown significance
• Modeling rare neurogenetic disorders, including microcephaly, using patient-specific brain organoids
• Dissecting disease mechanisms and therapeutic targets
• Patient outreach activities

RESEARCH THEME 4: Glioblastoma neurobiology and personalized glioblastoma invasion assays in brain organoids

• Recruiting patients and generation of Glioblastoma 3D tumoroids and biobanking
• Developing multi-omics
• Dissecting centrosomes and cilia abnormalities and targeting them
• Generating glioblastoma invasion assays in human brain organoids and patient stratification
• High content imaging and drug screening
• Validating them in preclinical models of patient-specific invasion assays

WE ARE GENEROUSLY SUPPORTED BY