Ling Hao

University of Maryland, College Park

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Lingjun Li

University of Wisconsin–Madison

Zhenhong Zhuang

Fujian Agriculture and Forestry University

Dandan Wu

Affiliated Hospital of Southwest Medical University

Yanfang Yao

Fujian Agriculture and Forestry University

Chi Yang

Fujian Academy of Agricultural Sciences

Yanling Yang

Fujian Agriculture and Forestry University

Yule Hu

Fujian Academy of Agricultural Sciences

Kangfu Ye

Academy of Military Medical Sciences

Wenwen Xin

Academy of Military Medical Sciences

Minghui Sun

Shanghai Jiao Tong University

Cooperative Institutions

National Institutes of Health

University of Wisconsin–Madison

National Institute of Neurological Disorders and Stroke

George Washington University

Fujian Agriculture and Forestry University

Capital Medical University

Chinese Academy of Sciences

Shanghai Jiao Tong University

Madison Group (United States)

University of Chinese Academy of Sciences

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RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether

SSRN Electronic Journal (2019)

Ya-Cheng Liao Michael S. Fernandopulle Guozhen Wang Heejun Choi Ling Hao

Long-distance RNA transport plays a critical role in cells by enabling local protein translation at metabolically-active sites distant from the nucleus. This ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a novel mechanism for RNA transport, in which RNA granules indirectly "hitchhike" on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as an adaptor between RNA granules and lysosomes. ANXA11 possesses an Nterminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. ALS-associated mutations in ANXA11 decrease long-range transport of RNA granules in neurons by disrupting their docking onto lysosomes. Thus, ANXA11 enables neuronal RNA transport via lysosomal hitchhiking of RNA granules, performing a critical cellular function that is disrupted in ALS.

Annexin A2

10.2139/ssrn.3312723

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Citations (17)

Contaminant Spot Check and Removal Assay (ContamSPOT) for Mass Spectrometry Analysis

Analytical Chemistry (2024)

Noah Smeriglio Haorong Li Wan Nur Atiqah binti Mazli Katharine Bendel Ling Hao

Mass spectrometry (MS) analysis is often challenged by contaminations from detergents, salts, and polymers that compromise data quality and can damage the chromatography and MS instruments. However, researchers often discover contamination issues only after they acquire the data. There is no existing contaminant assay that is sensitive enough to detect trace amounts of contaminants from a few microliters of samples prior to MS analysis. To address this crucial need in the field, we developed a sensitive, rapid, and cost-effective contaminant spot check and removal assay (ContamSPOT) to detect and quantify trace amounts of contaminants, such as detergents, salts, and other chemicals commonly used in the MS sample preparation workflow. Only 1 μL of the sample was used prior to MS injection to quantify contaminants by ContamSPOT colorimetric or fluorometric assay on a thin layer chromatography (TLC) plate. We also optimized contaminant removal methods to salvage samples with minimal loss when ContamSPOT showed a positive result. ContamSPOT was then successfully applied to evaluate commonly used bottom-up proteomic methods regarding the effectiveness of removing detergent, peptide recovery, reproducibility, and proteome coverage. We expect ContamSPOT to be widely adopted by MS laboratories as a last-step quality checkpoint prior to MS injection. We provided a practical decision tree and a step-by-step protocol with a troubleshooting guide to facilitate the use of ContamSPOT by other researchers. ContamSPOT can also provide a unique readout of sample cleanliness for developing new MS-based sample preparation methods in the future.

Sample Preparation

Trouble shooting

Sample (material)

10.1021/acs.analchem.3c05020

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Abstract 2418: PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis

Cancer Research (2018)

Fabao Liu Fengfei Ma Yuyuan Wang Ling Hao Hao Zeng

Abstract Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP3Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP3R-dependent mitochondrial functions Citation Format: Fabao Liu, Fengfei Ma, Yuyuan Wang, Ling Hao, Hao Zeng, Chenxi Jia, Yidan Wang, Peng Liu, Irene M. Ong, Baobin Li, Guojun Chen, Jiaoyang Jiang, Shaoqin Gong, Lingjun Li, Wei Xu. PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2418.

PKM2

Anaerobic glycolysis

Warburg Effect

10.1158/1538-7445.am2018-2418

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Growth Regulation and the Mechanism of Propiconazole in Maize Seedlings

ACTA AGRONOMICA SINICA (2017)

Ling Hao Jiapeng Xing Liusheng Duan Mingcai Zhang Zhaohu Li

Propiconazole

10.3724/sp.j.1006.2017.01603

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SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus

Dandan Wu Chi Yang Yanfang Yao Dongmei Ma Hong Lin

The epigenetic reader SntB was identified as an important transcriptional regulator of growth, development, and secondary metabolite synthesis in Aspergillus flavus . However, the underlying molecular mechanism is still unclear. In this study, sntB gene deletion (Δ sntB ), complementary (Com- sntB ), and HA tag fused to sntB ( sntB -HA) strains were constructed by using the homologous recombination method, respectively. Our results revealed that deletion of sntB inhibited the processes of mycelia growth, conidial production, sclerotia formation, aflatoxin synthesis, and ability to colonize host compared to wild type (WT), and the defective phenotype of knockout strain Δ sntB could be restored in its complementary strain Com- sntB . Chromatin immunoprecipitation sequencing (ChIP-seq) of sntB- HA and WT and RNA sequencing (RNA-seq) of Δ sntB and WT strains revealed that SntB played key roles in oxidative stress response of A. flavus . The function of catC (encode a catalase) gene was further analyzed based on the integration results of ChIP-seq and RNA-seq. In Δ sntB strain, the relative expression level of catC was significantly higher than in WT strain, while a secretory lipase encoding gene (G4B84_008359) was down-regulated. Under the stress of oxidant menadione sodium bisulfite (MSB), the deletion of sntB obvious down-regulated the expression level of catC . After deletion of catC gene, the mycelia growth, conidial production, and sclerotia formation were inhibited, while ROS level and aflatoxin production were increased compared to the WT strain. Results also showed that the inhibition rate of MSB to Δ catC strain was significantly lower than that of WT group and AFB1 yield of the Δ catC strain was significantly decreased than that of WT strain under the stress of MSB. Our study revealed the potential machinery that SntB regulated fungal morphogenesis, mycotoxin anabolism, and fungal virulence through the axle of from SntB to fungal virulence and mycotoxin bio-synthesis, i.e. H3K36me3 modification-SntB-Peroxisomes-Lipid hydrolysis-fungal virulence and mycotoxin bio-synthesis. The results of the study shed light into the SntB mediated transcript regulation pathway of fungal mycotoxin anabolism and virulence, which provided potential strategy for control the contamination of A. flavus and its aflatoxins.

Sterigmatocystin

10.7554/elife.94743.3

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SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis inAspergillus flavus

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Dandan Wu Chi Yang Yanfang Yao Dongmei Ma Hong Lin

Abstract The epigenetic reader SntB was identified as an important transcriptional regulator of growth, development, and secondary metabolite synthesis in Aspergillus flavus . However, the underlying molecular mechanism is still unclear. In this study, sntB gene deletion (Δ sntB ), complementary (Com- sntB ), and HA tag fused to sntB ( sntB -HA) strains were constructed by using the homologous recombination method, respectively. Our results revealed that deletion of sntB inhibited the processes of mycelia growth, conidial production, sclerotia formation, aflatoxin synthesis, and ability to colonize host, and the defective phenotype of knockout strain Δ sntB could be restored in its complementary strain Com- sntB . Chromatin immunoprecipitation sequencing (ChIP-seq) of sntB- HA and WT, and RNA sequencing (RNA-seq) of Δ sntB and WT strains revealed that SntB played key roles in oxidative stress response of A. flavus . The function of catC gene (encode a catalase) was further analyzed based on the integration results of ChIP-seq and RNA-seq. In Δ sntB strain, the relative expression level of catC was significantly higher than in WT strain, while a secretory lipase encoding gene (G4B84_008359) was down-regulated. Under the stress of oxidant menadione sodium bisulfite (MSB), the deletion of sntB obvious down-regulated the expression level of catC . After deletion of catC gene, the mycelia growth, conidial production, and sclerotia formation were inhibited, while ROS level and aflatoxin production were increased compared to the WT strain. Results also showed that the inhibition rate of MSB to Δ catC strain was significantly lower than that of WT group and AFB1 yield of the Δ catC strain was significantly decreased than that of WT strain under the stress of MSB. Our study revealed the potential machinery that SntB regulated fungal morphogenesis, mycotoxin anabolism, and fungal virulence through the axle of from SntB to fungal virulence and mycotoxin bio-synthesis, i.e. H3K36me3 modification-SntB-Peroxisomes-Lipid hydrolysis-fungal virulence and mycotoxin bio-synthesis. The results of this study shed light into the SntB mediated transcript regulation pathways of fungal mycotoxin anabolism and virulence, which provided potential strategy for control the contamination of A. flavus and its aflatoxins.

Sterigmatocystin

10.1101/2023.12.19.572357

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Correction: Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons

Molecular Neurodegeneration (2023)

Saadia Hasan Michael S. Fernandopulle Stewart W. Humble Ashley M. Frankenfield Haorong Li

Proteostasis

10.1186/s13024-023-00696-3

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Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure

Scientific Reports (2024)

Hewang Lee Bibhas Amatya Van Anthony M. Villar Laureano D. Asico Jin Kwon Jeong

Abstract The kidney and brain play critical roles in the regulation of blood pressure. Neuropeptide FF (NPFF), originally isolated from the bovine brain, has been suggested to contribute to the pathogenesis of hypertension. However, the roles of NPFF and its receptors, NPFF-R1 and NPFF-R2, in the regulation of blood pressure, via the kidney, are not known. In this study, we found that the transcripts and proteins of NPFF and its receptors, NPFF-R1 and NPFF-R2, were expressed in mouse and human renal proximal tubules (RPTs). In mouse RPT cells (RPTCs), NPFF, but not RF-amide-related peptide-2 (RFRP-2), decreased the forskolin-stimulated cAMP production in a concentration- and time-dependent manner. Furthermore, dopamine D1-like receptors colocalized and co-immunoprecipitated with NPFF-R1 and NPFF-R2 in human RPTCs. The increase in cAMP production in human RPTCs caused by fenoldopam, a D1-like receptor agonist, was attenuated by NPFF, indicating an antagonistic interaction between NPFF and D1-like receptors. The renal subcapsular infusion of NPFF in C57BL/6 mice decreased renal sodium excretion and increased blood pressure. The NPFF-mediated increase in blood pressure was prevented by RF-9, an antagonist of NPFF receptors. Taken together, our findings suggest that autocrine NPFF and its receptors in the kidney regulate blood pressure, but the mechanisms remain to be determined.

Fenoldopam

10.1038/s41598-024-64484-9

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Citations (1)

Generation of serotonin neurons from human pluripotent stem cells

Nature Biotechnology (2015)

Jianfeng Lü Xuefei Zhong Huisheng Liu Ling Hao Cindy Huang

Tryptophan hydroxylase

Raphe nuclei

Monoaminergic

10.1038/nbt.3435

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