In this study we used a mouse model of acute lymphoblastic leukemia, the most common pediatric malignancy, to identify the components of an immune response that are necessary to achieve a long-lasting remission. We found that while a response directed against a single target antigen was able to exert early control over leukemia, it was not sufficient to sustain remission; prolonged survival required that the immune response...
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In this study we inserted lumbar drains in patients with acute SCI, and evaluated how monitoring of the cerebrospinal fluid (CSF) pressure around the spinal cord could assist in optimizing the hemodynamic management of these patients.    By showing that the monitoring of CSF pressure (and subsequent calculation of spinal cord perfusion pressure) was a better predictor of neurologic improvement than our standard monitoring...
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The bacterial flagellum is a complex multi-component structure including a whip-like appendage, the flagellar filament, which is composed of approx. 20,000 protein units (flagellins) that link up together and form a structure of about 10 micrometers in length. We discovered and characterized a new family of flagellins...
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First, we show that models of depression in mouse produce brain function changes resembling those observed in humans who are depressed. This, of course, opens up the possibility of testing questions that are prohibitive in humans. As such, we used a next generation fluorescent sensor that allowed us to look at a specific neurotransmitter system...
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Engineered T-cell receptors (TCRs) have tremendous therapeutic potential for targeted, T-cell-mediated killing of infected or malignant cells. A key hurdle in realizing this vision is understanding and manipulating the interactions of TCRs with their cognate antigens. Rules for TCR engagement have been difficult to define owing to the complexity of the system, and platforms for de novo TCR design remain aspirational. A…
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Cancers, including Hodgkin lymphoma can change their face over time. Specifically in Hodgkin lymphoma, we have shown that the so called tumor microenvironment changes form initial diagnosis to relapse. This has implications for prognostication, treatment resistance and the rational choice of therapies in the era of personalized medicine. In the Journal of Clinical Oncology publication, we have developed  an assay, called RHL30, at the time point of disease relapse when testing is most needed for physicians...
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Due to their unique optical and electromagnetic properties, inorganic nanoparticles are extremely promising for therapeutics as well as diagnostics (theranostics: therapeutic + diagnostic). For example, iron oxide nanoparticles can be used as an MRI contrast agent but also can generate heat when stimulated by an external electromagnetic and can be used to destroy cancer...
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We present the structures of Type IV pili from two bacterial pathogens of major medical importance, Pseudomonas aeruginosa and Neisseria gonorrhoeae. P. aeruginosa use Type IV pili to adhere to the lungs of cystic fibrosis patients, causing deadly infections, and N. gonorrhoeae use their Type IV pili to adhere to and invade cells of the urogenital tract to cause the sexually transmitted disease gonorrhea. These Type IV pili...
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Death by HDAC Inhibition in Synovial Sarcoma Cells

In synovial sarcoma, there is a known oncogene, SS18-SSX, but we have no drugs that target it directly. We have found that SS18-SSX acts by changing the epigenome, and it does so by hijacking and redirecting the activity of enzymes that modify histones. We found that a histone deacetylase inhibitor, quisinostat, is able to reverse some of the oncogenes changes, break up the abnormal complexes it forms, and kills synovial sarcoma cells in vitro and in a new mouse...
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A key challenge to traditional genome wide association studies (GWAS) is that many identified genetic variants lie outside the protein coding regions, hence their functions are difficult to determine. To address this challenge, we performed quantitative trait locus (QTL) analyses on one of the largest multi-omic datasets for brain tissues, which comprises gene expression, DNA methylation, and histone modification...
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