The Habib Lab works at the intersection of stem cell biology, biophysics, and tissue engineering to investigate how tissues form. They use this knowledge to develop technologies for tissue repair.
Wnt proteins (Wnts), often secreted locally, are required for self-renewal in many types of stem cells. Shukry pioneered a technology to immobilise hydrophobic Wnts to synthetic surfaces (Science 2013, Nature Protocols 2017), thereby allowing Wnts to be spatially targeted to cells and tissues. Shukry demonstrated how localised and directional Wnts affect mammalian stem cells by inducing asymmetric stem cell division (Science 2013), an essential process for tissue formation. His lab has shown that Wnt-platforms can select for and self-renew Wnt-responsive stem cells (Stem Cell Reports 2016). Using this, they engineered the Wnt-induced osteogenic tissue Model (WIOTM), which maintains human skeletal stem cells (hSSCs) and a cascade of osteogenic differentiating cells, a process driven by asymmetric cell division. This system is ideal for modelling human bone diseases and drug screening. Importantly, they engineered a novel Wnt-bandage and formed the WIOTM on it (WIOTM-bandage). Wnt-bandage treatment doubles bone repair, while the WIOTM-bandage triples bone repair, in critical-sized bone defects that cannot heal by themselves. Importantly, hSSCs are maintained in vivo and uniquely generate human mature bone cells (Nature Materials 2020). A patent, interest from orthopaedic surgeons for clinical trials, and over 107 news articles have resulted, including televised coverage by CBS news.
The Habib lab studies mechanisms of stem cell self-organisation to generate 3D tissues. They identified specialized cytonemes that “seek” self-renewal-promoting Wnt-ligands and pair with niche Wnt-producing cells to initiate morphogenesis. They discovered a unique glutamate-Wnt receptor cross-talk during Wnt recruitment as a mechanism of cytoneme selectivity (PNAS 2020), which they further characterised using statistical mechanics (Physical ReviewX 2020). The Habib lab highlighted roles of Wnt-signalling components and Glutamate receptors, in cytoneme formation, Wnt-interaction and Wnt-mediated asymmetric stem cell division (e-Life; under review & JCB 2021), alongside discovering asymmetric inheritance of histones (Cell Reports 2020, STAR Prot. 2020). In summary the Habib lab, in collaboration with international labs, ventures in new areas of science by building on Shukry’s previous work, resulting in novel technologies for Musculoskeletal tissues growth and repair and insights into early embryogenesis.
© 2016 by Shukry Habib.