Wei Gu, MD, PhD, is a board-certified pathologist at UCSF. His research focuses on minimally invasive diagnostics using cell-free DNA/RNA with an emphasis on infectious disease, oncology, and prenatal diagnostics. He received his Bioengineering MD/PhD from Stanford University working with Dr. Stephen Quake on cell-free prenatal (NIPT) and cancer diagnostics. Dr. Gu completed his Clinical Pathology residency and Molecular Genetic Pathology fellowship at UCSF.

Jenner Institute: "Malaria Vaccines – quite a challenge", Prof Adrian Hill -- Silver Star: Chair: Prof Richard Cornall

Forced expression of defined transcription factors leads to the direct conversion of various cell types into induced neurons (iNs). Specifically, successful reprogramming of resident brain astrocytes in vitro as well as in vivo represents a great advantage for the generation of neurons and derived circuits. However, whether astrocytes from distinct brain regions might show a reprogramming specificity towards a unique iN type remains largely unknown. Here, we use direct reprogramming of thalamic astrocytes by Neurog2 to generate specific excitatory sensory-modality thalamocortical neurons. Moreover, we show that the origin, but not the environment of the astrocytes determines the fate of the iNs after direct reprogramming. Indeed, clonal analysis in the thalamus shows that astrocytes from the distinct thalamic nuclei are clonally related determining the specificity of the iNs generated from those astrocytes. We also found that the potential of the same transcription factor to reprogram nuclei-specific thalamic astrocytes into precise subsets of thalamocortical neurons depends on particular epigenetic modifications. In sum, our study provides novel insights into the mechanisms that control the specification of thalamic neurons and importantly those that are required for direct programming of sensory neurons. Generation of specific sensory brain circuits might be an approach for future rehabilitation strategies.

T cell-dependent immunity commences with T-cell antigen receptor (TCR-CD3) signalling. TCR-CD3 features unique ligand recognition, signalling modalities and convoluted quaternary structure, diverging considerably from “classic”, evolutionary ancient membrane receptors of simpler molecular design and univocal relationship to ligands. TCR-CD3 recognises with exceptional sensorial and discriminatory ability antigens of varying structure, quantity and detection context. Given such a complexity, it is perhaps unsurprising that controversy exists on how TCR-CD3 works. I will report new data suggesting an allosteric mechanism by which TCR-CD3 transmits signals across the plasma membrane that should improve our understanding of how T cell activation begins.

Recent technological advances now enable in-depth assessment of blood based 'omic' markers at scale and can provide important insights into the aetiology of metabolic and other diseases. Existing studies are limited by their design, size, analytical strategy and single disease focus. We combine large-scale genomic with metabolomic and proteomic data to define the genetic architecture of thousands of ‘omic’ traits. We integrate data from different platforms and studies to maximise power for the identification of genetic variants associated with life-long differences in metabolite and protein levels and enable investigation of their relevance for disease aetiology and prediction, with a specific focus on type 2 diabetes and related traits.

Combined Medical-Surgical Grand Round: Chair: TBA