Prof Penny Handford

Prof Penny Handford


We investigate how mammalian cells interact with their extracellular environment in health and disease

Prof Penny Handford

cbEGF containing proteins in health and disease

My group has two main interests:


  1.  Understanding Notch receptor activation. We aim to understand the cell surface organisation of the Notch receptor, its interaction with ligands, and its regulation using a range of molecular, cellular and whole organism methods. The Notch pathway is a universally conserved signaling system in metazoan organisms. Not only does it play a key role in development, but the pathway also regulates cell proliferation, apoptosis and angiogenesis.  Many diseases including a range of cancers  arise as a result of gene mutations  in Notch pathway components. By understanding the molecular mechanisms involved in receptor -ligand recognition and activation, we hope that novel therapies will be developed to modulate the Notch signal in different biological processes.
  2. The role of fibrillin-1 microfibrils in regulating TGFß activation, a crucial extracellular matrix cytokine.We also study the structure, assembly and interactions of the extracellular matrix fibrillins, and the mechanisms by which disease-causing mutations result in the connective tissue disorders Marfan syndrome and the acromelic dysplasias. Our recent structural studies have enabled us to create a GFP-labelled form of fibrillin-1. This has allowed us to track the fate of normal and mutant fibrillin-1 forms in the process of microfibril assembly using a co-culture system We are also currently studying fibrillin-1 intermolecular interactions with the LTBPs in order to gain insight into the role of the fibrillin microfibril matrix in regulating the process of TGFß activation.

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