Aimee L. Edinger

Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke

Azzurra Cottarelli, Danny Jamoul, Mary Claire Tuohy, Sanjid Shahriar et autres

The integrity of adherens and tight junctions is critical for blood-brain barrier (BBB) function in the healthy brain. Disassembly of cell junctions due to degradation of adherens and tight junction-associated proteins leads to acute BBB dysfunction after ischemic stroke, but the mechanisms …

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Mevalonate Biosynthesis is a Metabolic Vulnerability of Gemcitabine-resistant Pancreatic Cancer

Alica K. Beutel, S. Calderón, Ethan Nghiem, Kevin Christian Montecillo Gulay et autres

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a devastating prognosis. Gemcitabine, a pyrimidine anti-metabolite, is a cornerstone in PDAC therapy. However, resistance remains a major hurdle in clinical care. Resistance can arise from microenvironmental metabolites or through direct metabolic …

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Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A

Vaishali Jayashankar, Peter Kubiniok, Alison N. McCracken, Rebeca G Gentry et autres

Sphingosine and constrained analogs like FTY720 and SH-BC-893 restrain tumor growth through incompletely defined mechanisms that include protein phosphatase 2A (PP2A) activation. Here we show that these compounds directly bind not only the PP2A scaffolding subunit PPP2R1A, but also the structurally related …

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CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy

Rebecca Lim, Ailing Lu, Brennan M. Chuang, Cecily Anaraki et autres

Macropinocytosis is reported to fuel tumor growth and drug resistance by allowing cancer cells to scavenge extracellular macromolecules. However, accurately defining the role of macropinocytosis in cancer depends on our ability to selectively block this process. 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) is widely used to …

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Abstract C045: Targeting metabolic heterogeneity in pancreatic ductal adenocarcinoma

Taryn Morningstar, Cecily Anaraki, Lorenzo Scipioni, G Tedeschi et autres

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the US. This poor prognosis is related to the complex tumor microenvironment and tumor heterogeneity that drives resistance to chemotherapy. Here the heterogeneity of the stromal, immune, and …

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Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients

Varvara I. Rubtsova, Yujin Chun, Joo‐Hwan Kim, Cuauhtemoc B. Ramirez et autres

Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the …

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A high dose KRP203 induces cytoplasmic vacuoles associated with altered phosphoinositide segregation and endosome expansion

Satoshi Kofuji, Kara Wolfe, Kazutaka Sumita, Shun Kageyama et autres

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Abstract B071: A genetic approach to selectively inhibit macropinocytosis while sparing autophagy

Rebecca Lim, Brandon Chu, Aimee L. Edinger

Abstract Macropinocytosis is a bulk endocytic process that can fuel tumor growth and drug resistance by providing access to extracellular protein and necrotic cell debris. This process is primarily studied by utilizing the chemical inhibitor, 5-(N-ethyl-N-isopropyl)-Amiloride (EIPA), but this inhibitor is nonselective …

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Diversifying faculty recruitment in biomedical sciences

Michael A. Yassa, Aimee L. Edinger

A wealth of data has consistently demonstrated that a diverse faculty maximizes productivity and innovation in the research enterprise and increases the persistence and success of groups that are underrepresented in STEM. While the diversity of students in graduate programs has steadily …

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Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke

Azzurra Cottarelli, Danny Jamoul, Mary Claire Tuohy, Sanjid Shahriar et autres

SUMMARY Adherens (AJ) and tight junction (TJ) integrity is critical for blood-brain barrier (BBB) function in the healthy brain. Junction disassembly due to degradation of AJ and TJ proteins leads to acute BBB dysfunction after ischemic stroke, but the mechanisms are not …

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Disruption of the Rab7-Dependent Final Common Pathway of Endosomal and Autophagic Processing Results in a Severe Podocytopathy

Kristin Vöing, Ulf Michgehl, Nils David Mertens, Cara Picciotto et autres

SIGNIFICANCE STATEMENT: Endocytosis, recycling, and degradation of proteins are essential functions of mammalian cells, especially for terminally differentiated cells with limited regeneration rates and complex morphology, such as podocytes. To improve our understanding on how disturbances of these trafficking pathways are linked …

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Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics

Brendan T. Finicle, Kazumi Eckenstein, Alexey S. Revenko, Brooke A. Anderson et autres

Inefficient endosomal escape remains the primary barrier to the broad application of oligonucleotide therapeutics. Liver uptake after systemic administration is sufficiently robust that a therapeutic effect can be achieved but targeting extrahepatic tissues remains challenging. Prior attempts to improve oligonucleotide activity using …

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