Venom-inspired design of novel peptide drug leads for diabetes and pain
Helena Safavi-Hemami
Associate Professor, University of Utah
Peptide hormones and neuropeptides, collectively referred to as signaling peptides, play critical roles in human health and disease and are important molecules for drug development. However, several biophysical properties severely limit the usefulness of native signaling peptides as therapeutics. These include poor in vitro and in vivo stability and lack of selectivity for receptors that belong to closely related families. Optimized by millions of years of evolution, venomous animals have generated toxins that mimic the endogenous signaling peptides of their prey and predators. Because of their streamlined role in manipulating the physiology of another organism, these “doppelganger toxins” exhibit several advantageous properties that render them ideal candidates for drug development. Here, I will give an overview of the diversity of doppelganger toxins in venomous cone snails and highlight how our discovery of toxins that mimic insulin and somatostatin inspired the design of new drug leads for diabetes and pain.
Helena Safavi is an Associate Professor of Biochemistry at the University of Utah in Salt Lake City. Dr. Safavi studied biology at the University of Cologne (Germany) and the Australian Institute of Marine Sciences in Townsville (Australia). She obtained her PhD in Biochemistry and Molecular Biology at the University of Melbourne (Australia) in 2011 where she was trained in the transcriptomics and proteomics identification of bioactive peptides from animal venoms under the supervision of Prof. Anthony Purcell. Following her PhD studies Dr. Safavi received a Marie Curie Postdoctoral Fellowship to conduct a joined research project on the large-scale identification and biomedical characterization of peptide toxins and biosynthetic enzymes with Lars Ellgaard at the University of Copenhagen (Denmark) and Toto Olivera at the University of Utah (USA). During this time, she discovered that predatory cone snails use insulin-like toxins to induce dangerously low blood sugar in their fish prey, a discovery that inspired the design of new fast-acting insulin drug leads for the treatment of diabetes. Having had broad training in the characterization of bioactive peptides from animal venoms, her independent research focuses on the identification of hormone-like toxins as drug leads for the treatment of diabetes and pain. Her group’s recent findings on a novel class of somatostatin-like toxins elucidated an ancient origin of the somatostatin signaling system in animals and has led to the design of several stable and selective somatostatin analogs that provide analgesia in mouse models of acute and chronic pain.