The Nelson lab’s primary research focus is on prostate cancer, the second most common malignancy in men worldwide. The molecular landscape of prostate cancer is complex, and our lab works to identify and understand the underlying drivers which may inform treatment strategies for patients living with this disease. Further, we aim to elucidate the role of the tumor microenvironment in therapeutic resistance and develop a comprehensive understanding of disease progression.
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In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute to chronic infection. To form aggregates, P. aeruginosa can use different mechanisms, each with its own pathogenic implications. However, how they form in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix that holds the aggregates together. Pel and Psl exopolysaccharides are structural and protective components of…
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Intracellular pathogens alter their host cells’ mechanics to promote dissemination through tissues. Conversely, host cells may respond to the presence of pathogens by altering their mechanics to limit infection. Here, we monitored epithelial cell monolayers infected with intracellular bacterial pathogens, Listeria monocytogenes or Rickettsia parkeri, over days. Under conditions in which these pathogens trigger innate immune signaling through NF-κB and…
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Compartmentalization of Phosphatidylinositol 4,5-Bisphosphate Metabolism Into Plasma Membrane Liquid-Ordered/Raft Domains

Lipids of bilayer membranes can segregate laterally into distinct liquid phases of different composition called liquid ordered and liquid disordered, and corresponding in the plasma membrane of living cells to nanodomains called raft and nonraft domains. Using Förster resonance energy transfer and genetically expressible protein probes of lipid domains, we find that several steps of the metabolism of phosphoinositide lipids…
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Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent–child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic variation even across complex loci. We identify 107,590 structural variants (SVs), of which 68% are…
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The work discussed here highlights our work on gap junctions. Gap junctions are highly organized membrane domains, consisting of thousands of intercellular channels, made up of connexin proteins. The cytoplasmic tails of these proteins interact with a wide variety of kinases and signaling molecules providing a scaffold function at the plasma membrane. Thus, gap junctions can couple intercellular communication with intracellular signaling.
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The research in our lab focuses on the smallest blood vessels that deliver oxygen and nutrients to the brain. In the human brain, an estimated 400 miles of blood vessels deliver blood to 100 billion neurons. This immensely complex task can easily go awry during human disease. We use an imaging approach called in vivo two-photon microscopy and mouse models to study how blood vessels grow, degrade, and respond to injury from birth to senescence.
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The Krüppel-Like Factor Cabut Has Cell Cycle Regulatory Properties Similar to E2F1

Using a gain-of-function screen in Drosophila, we identified the Krüppel-like factor Cabut (Cbt) as a positive regulator of cell cycle gene expression and cell proliferation. Enforced cbt expression is sufficient to induce an extra cell division in the differentiating fly wing or eye, and also promotes intestinal stem cell divisions in the adult gut. Although inappropriate cell proliferation also results…
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There is increasing interest in targeting CD33 in malignant and non-malignant disorders. In acute myeloid leukemia, longer survival with the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO) validates this strategy. Still, GO benefits only some patients, prompting efforts to develop more potent CD33-directed therapeutics. As one limitation, CD33 antibodies typically recognize the membrane-distal V-set domain. Using various artificial CD33 proteins, in…
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BRCA1/BARD1 Site-Specific Ubiquitylation of Nucleosomal H2A Is Directed by BARD1

Mutations in the E3 ubiquitin ligase RING domains of BRCA1/BARD1 predispose carriers to breast and ovarian cancers. We present the structure of the BRCA1/BARD1 RING heterodimer with the E2 enzyme UbcH5c bound to its cellular target, the nucleosome, along with biochemical data that explain how the complex selectively ubiquitylates lysines 125, 127 and 129 in the flexible C-terminal tail of…
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