Despite increased focus on the clinical relevance of dormant metastatic disease, our understanding of dormant niches, mechanisms underlying emergence from dormancy, and the immune system’s role in this phenomenon, remains in its infancy. Here, we discuss key work that has shaped our current understanding of these topics. Because tumour dormancy provides a unique therapeutic window to prevent metastatic disease, we…
Natural proteins evolved over billions of years to solve biology’s most complex problems. But we face new and pressing challenges today. The goal of my lab at the UW Institute for Protein Design is to develop and apply methods for designing a whole new world of synthetic proteins to address 21st-century challenges in precision medicine, energy production, manufacturing, and more. We combine computer science and molecular biology to design novel proteins from first principles that can serve as medicines, vaccines, catalysts, biomaterials, sensors, and beyond...
Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin-gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRPPBN neurons to either the central nucleus of the amygdala or the bed…
Our team focuses on pediatric brain tumor therapeutics and the discovery of novel peptide therapeutics for a variety of diseases. We discovered “Tumor Paint”, a scorpion-derived peptide that delivers fluorescent markers to cancer cells. Stemming from that work, the investigational agent Tozuleristide (Blaze Bioscience) is now entering a nationwide clinical trial that could potentially lead to FDA registration. We are now using the patient-derived mouse models described in the Nature Medicine paper to prioritize treatment strategies for the types of brain tumors that most often lead to death in children...
We developed a computer-aided analysis tool for quantitatively determining bioluminescent reporter distributions inside small animals. The core innovations are a body-fitting animal shuttle and a statistical mouse atlas, both of which are spatially aligned and scaled according to the animal’s weight, and hence provide data congruency across animals of varying size and pose. In conjunction with a multispectral bioluminescence tomography…
The connexin family of channel-forming proteins is present in every tissue type in the human anatomy. Connexins are best known for forming clustered intercellular channels, structurally known as gap junctions, where they serve to exchange members of the metabolome between adjacent cells. In their single-membrane hemichannel form, connexins can act as conduits for the passage of small molecules in autocrine…
Our paper shows how brain chemistry relates to neural responses, and ultimately to how people perceive visual motion. Using MR spectroscopy, we can measure an index of glutamate, which is a neurotransmitter that affects brain activity. We showed that the amount of glutamate in a particular part of the brain that processes visual motion (called area MT) is related to the strength of the fMRI response (an index of neural activity)...
Animals rely on an internal sense of body position and movement to effectively control motor behavior. This sense of proprioception is mediated by diverse populations of mechanosensory neurons distributed throughout the body. Here, we investigate neural coding of leg proprioception in Drosophila, using in vivo two-photon calcium imaging of proprioceptive sensory neurons during controlled movements of the fly tibia. We found…
Stimulus- or context-dependent routing of neural signals through parallel pathways can permit flexible processing of diverse inputs. For example, work in mouse shows that rod photoreceptor signals are routed through several retinal pathways, each specialized for different light levels. This light-level-dependent routing of rod signals has been invoked to explain several human perceptual results, but it has not been tested…
Darwin famously thought of evolution as a force for creation and improvement. Evolution, in his eyes, was synonymous with natural selection and survival of the fittest – a process that optimizes life to thrive in its environment and produce greater numbers of offspring. A century later, however, the great population geneticist Motoo Kimura challenged this view with his ‘neutral theory’…