When the Damage Is Done: Injury and Repair in Thymus Function

Even though the thymus is exquisitely sensitive to acute insults like infection, shock, or common cancer therapies such as cytoreductive chemo- or radiation-therapy, it also has a remarkable capacity for repair. This phenomenon of endogenous thymic regeneration has been known for longer even than its primary function to generate T cells, however, the underlying mechanisms controlling the process have been…
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Aggregation of the beta cell secretory product human islet amyloid polypeptide (hIAPP) results in islet amyloid deposition, a pathological feature of type 2 diabetes. Amyloid formation is associated with increased levels of islet IL-1β as well as beta cell dysfunction and death, but the mechanisms that promote amyloid deposition in situ remain unclear. We hypothesised that physiologically relevant concentrations of…
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SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However,…
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Engineering Heart Morphogenesis

There is high potential for current technologies to be used to recapitulate heart development in vitro by focusing on its earliest stage of morphogenesis: the embryonic heart tube. Recent advances in stem cell biology have enabled the production of cardiac progenitor lineages for bioengineering approaches. Biofabrication techniques can create structures and features of the heart tube at the appropriate scale. Biochemical cues…
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The Tian Laboratory focuses on the roles of cell metabolism and mitochondrial function in the pathogenesis of human diseases. We take multidisciplinary approaches to engineer and interrogate the metabolic network in both cellular and animal models. Our ability to target molecular regulatory mechanisms in combination of rigorous metabolic phenotyping has led to groundbreaking discoveries in cardiometabolic research.
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Natural killer (NK) cells belong to the innate immune system and contribute to protecting the host through killing of infected, foreign, stressed or transformed cells. Additionally, via cellular cross-talk, NK cells orchestrate antitumor immune responses. Hence, significant efforts have been undertaken to exploit the therapeutic properties of NK cells in cancer. Current strategies in preclinical and clinical development include adoptive…
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Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to degeneration of the Y chromosome. The progression of degeneration is not well understood, as complete sequence assemblies of heteromorphic Y chromosomes have only been generated across a handful of taxa with highly degenerate sex chromosomes. Here, we describe the assembly of…
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The authors observed that virus-specific CAR T-cells were less functional in vivo, relative to CAR T-cells used for cancer. They hypothesized that the difference was due to levels of target antigen: CARs for cancer encounter very high levels of cell-associated antigen, whereas HIV-infected individuals on suppressive antiretroviral therapy have extremely low levels of antigen. To address this, they co-delivered a cell-associated antigen source, and were excited to see robust expansion of our CAR T cells and clear correlates of antiviral function.
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We study a small molecule (NSAC1003) that one of our collaborators (Ryan Cirz) at Achaogen, Inc., found in a screen for inhibitors of the E. coli DNA break repair enzyme RecBCD, a helicase-nuclease.  This compound mimics two RecBCD mutations that make RecBCD cut DNA at novel positions much like the uninhibited, wild-type enzyme cuts at Chi hotspots of genetic recombination.  The novel cuts are at a certain percent of the length of the DNA substrate used in the assay.
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Dissemination of transformed cells is a key process in metastasis. Despite its importance, how transformed cells disseminate from an intact tissue and enter the circulation is poorly understood. Here, we use a fully developed tissue, Drosophila midgut, and describe the morphologically distinct steps and the cellular events occurring over the course of RasV12-transformed cell dissemination. Notably, RasV12-transformed cells formed the Actin- and Cortactin-rich invasive…
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