Chunni Zhu

Abstract PS1-12-12: Comparative transcriptomic and proteomic analysis of lasofoxifene and fulvestrant, in an ER-mutated metastatic breast cancer explant model, identifies potential molecular mechanisms underlying differential treatment efficacy

M. Laine, D. A. Tieri, Chunni Zhu, I. Raman et autres

Abstract Background: Metastatic breast cancer (mBC) is one of the leading causes of death among women. Mutations in estrogen receptor alpha (ERα) are acquired as the disease becomes resistant to current therapies, leading to tumor cell metastasis to distant organs. A combination …

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Ferumoxytol-Enhanced Cardiac Magnetic Resonance for Delineation of Hyperacute Intramyocardial Hemorrhage With Ex Vivo Validation

Arutyun Pogosyan, Caroline M. Colbert, Mostafa Mahmoudi, Mary Keushkerian et autres

OBJECTIVES: Intramyocardial hemorrhage (IMH) is the most severe form of injury associated with reperfusion therapy during acute myocardial infarction (AMI). Although T2*-weighted cardiac MRI is regarded as the reference standard for IMH detection, its application is limited in the hyperacute phase. Ferumoxytol, …

MI-181 enhances ciliation and cilia length in a cigarette smoke exposed airway epithelial model

Ankur A. Gholkar, Caroline Cherry, Thomas V. Gimeno, Claire Nocon et autres

Multiciliated airway epithelial cells possess motile cilia, which are essential for mucociliary clearance, facilitating the removal of particulates from the respiratory system. Previous studies showed that exposure to cigarette toxins causes damage to motile cilia formation, length, and function, and can lead …

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Discovery of an ApoE4‐Targeted Small‐Molecule SirT1 Enhancer for the Treatment of Alzheimer’s Disease

Samar Padder, Jesus Campagna, Sujyoti Chandra, Bruce Teter et autres

BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid plaques and tau tangles, with apolipoprotein E4 (ApoE4) recognized as a strong genetic risk factor for sporadic AD. ApoE4 has been shown to repress the expression of Sirtuin 1 (SirT1), a key neuroprotective protein, …

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Small Molecule of Secreted Clusterin Promotes Mitochondrial Function, Synaptic Plasticity and Improved Memory in an Alzheimer's Disease Mouse Model

Samar Padder, Whitaker Cohn, Jesus Campagna, Dongwook Wi et autres

BACKGROUND: Clusterin (CLU) is a key genetic risk factor for late-onset Alzheimer's disease (AD). Its secreted clusterin isoform (sCLU) is neuroprotective, promoting amyloid beta (Aβ) and tau clearance, reducing oxidative stress, and modulating immune responses, while the nuclear form (nCLU) is neurotoxic. …

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Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease

Jesus Campagna, Barbara Jagodzinska, Dongwook Wi, Chunni Zhu et autres

Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1) has been a target for Alzheimer's disease (AD) therapeutic development. Here, we report our identification of APP-selective BACE1 (ASBI) inhibitors that are selective for APP as the substrate and BACE1 as …

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Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice

Whitaker Cohn, Jesus Campagna, Dongwook Wi, Jessica Lee et autres

Despite substantial research and drug discovery efforts, Alzheimer's Disease (AD) remains the sixth leading cause of death in the United States, underscoring the urgent need for novel therapeutic targets. A mutation in the clusterin (CLU) gene that hinders expression of the cyto-protective …

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Discovery of an ApoE4-targeted small-molecule SirT1 enhancer for the treatment of Alzheimer’s disease

Jesus Campagna, Sujyoti Chandra, Bruce Teter, Whitaker Cohn et autres

Decreased expression of sirtuin 1 (SirT1) has been implicated in Alzheimer's disease (AD), and as we previously reported, is related to transcriptional repression by the major risk factor for sporadic AD, apolipoprotein E4 (ApoE4). Herein we describe the discovery of an orally …

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Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein

Hope Pan, Melinda Balbirnie, Ke Hou, Naomi S. Sta Maria et autres

Aggregation of the protein α-synuclein (α-syn) is the histopathological hallmark of neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Currently, patients with synucleinopathies are diagnosed by physical …

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A Therapeutic Small Molecule Enhances γ‐Oscillations and Improves Cognition/Memory in Alzheimer’s Disease Model Mice

Xiaofei Wei, Jesus Campagna, Barbara Jagodzinska, Dongwook Wi et autres

Abstract Background Brain rhythms provide the timing for recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks. The γ‐oscillations (30‐120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. High temporal resolution recording methods, such as …

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A therapeutic small molecule enhances γ-oscillations and improves cognition/memory in Alzheimer’s disease model mice

Xiaofei Wei, Jesus Campagna, Barbara Jagodzinska, Dongwook Wi et autres

Brain rhythms provide the timing for recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks. The γ-oscillations (30 to 120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological …

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Successful Gene Editing of Apolipoprotein E4 to E3 in Brain of Alzheimer Model Mice After a Single IV Dose of Synthetic Exosome-Delivered CRISPR

Bruce Teter, Jesus Campagna, Chunni Zhu, Grace E. McCauley et autres

Abstract Background The gene for apolipoprotein E4 (ApoE4 E4) confers an increased risk for development and lowers the age of onset of Alzheimer’s disease (AD), and is a highly suitable target for CRISPR-based editing because ApoE4 differs from ApoE3 by a single …

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