About

Ming Guo is a professor in the Pharmacology Department at the University of California, Los Angeles. His laboratory investigates molecular genetic mechanisms underlying the two most common neurodegenerative disorders, Alzheimer’s disease (AD) and Parkinson’s disease (PD). His research aims to understand disease mechanisms and translate findings into human studies. A key focus is on the pathological hallmark of AD, amyloid plaques composed of the toxic peptide A-beta, which is generated from the Amyloid Precursor Protein (APP) through the action of proteases including gamma-secretase with Presenilins as the catalytic core. His team has developed an in vivo reporter system to identify regulators of APP levels and gamma-secretase activities via genome-wide genetic screens, leading to the identification of multiple enhancers and suppressors of this reporter, with ongoing characterization of these genes for potential diagnostic and therapeutic applications. In the realm of PD, Ming Guo's work includes pioneering research on mutations in PINK1 and PARKIN, which result in autosomal recessive forms of the disease. His team was among the first worldwide to report the function of PINK1 and to discover that PINK1 and PARKIN operate in a common genetic pathway to regulate mitochondrial integrity and quality control, partly through the regulation of mitochondrial fusion and fission dynamics. Recently, his research identified MUL1, a gene that, when overexpressed, suppresses mitochondrial defects related to PINK1/PARKIN mutations, and when deleted, exacerbates these defects. MUL1 acts in parallel pathways to PINK1/PARKIN to degrade Mitofusin, a pro-mitochondrial fusion protein, with increased Mitofusin levels causing cell death and mitochondrial damage. His work has implications for aging and other neurodegenerative, heart, and metabolic disorders, emphasizing the importance of optimizing MUL1 and Mitofusin levels as potential therapeutic targets.

Research topics

• Biology
• Cell biology
• Genetics
• Chemistry
• Cancer research

Selected publications

• FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein–protein interaction

  Nucleic Acids Research · 2026-04-10

  articleOpen access

  Transcription factor nuclear factor of activated T cells (NFAT) plays a central role in immune gene regulation through cooperative interactions with diverse transcriptional partners. While FOXP family members have been identified as co-regulators of NFAT1, the involvement of other FOX family proteins has remained mechanistically obscure. Here, we solved three crystal structures of NFAT1-RHR/FOXC2-DBD/ARRE DNA ternary complexes and uncovered an unexpected mode of transcriptional repression mediated by FOXC2 through direct, DNA-facilitated binding to the V-shaped groove of NFAT1's Rel-homology region (RHR). Biochemical assays revealed that DNA enhanced FOXC2-NFAT1 interaction by more than five-fold, supporting a model in which DNA acts as a structural co-factor that promotes complex formation. Mutational disruption of the FOXC2-NFAT1 interface impaired complex assembly and abrogated transcriptional repression. Functional assays further confirmed that FOXC2 suppressed NFAT1-driven transcription of multiple cytokines and chemokines, including IL2, TNF, CXCL5, and CCL2. Notably, this repressive mechanism was found to extend to other FOX proteins (FOXI1, FOXO1, and FOXK1), suggesting a broader paradigm of FOX-NFAT1 interaction. Our study defined a previously unrecognized FOX-mediated transcriptional repression mechanism and provides a structural framework for NFAT inhibition by FOX proteins, offering novel insights into the transcriptional regulation of immune-related genes.

  PublisherDOI

• The Essentials of PgPG1, a Polygalacturonase-Encoding Gene for the Invasion of Pyrenophora graminea to Hordeum vulgare

  International Journal of Molecular Sciences · 2025-03-07 · 4 citations

  articleOpen access

  Barley leaf stripe, caused by Pyrenophora graminea, significantly reduces yield. Polygalacturonase, a key fungal pectinase, facilitates cell wall degradation for nutrition acquisition and colonization. To determine whether P. graminea contains polygalacturonase (PgPG)-encoding genes and their role in pathogenicity, four PgPG genes (PgPG1–PgPG4) were identified in the P. graminea genome. Quantitative RT-PCR revealed that PgPG1 had the highest inducible expression during barley infection, suggesting its critical vital role in pathogenesis. PgPG1 was silenced and overexpressed in P. graminea QWC (wild-type) using CaCl2-PEG4000-mediated protoplast transformation. The PgPG1 RNAi mutants exhibited slower growth, while overexpression mutants grew faster. Relative to the wild-type, the disease incidence of Alexis, a highly susceptible barley variety, decreased by 62.94%, 42.19%, 45.74%, and 40.67% for RNAi mutants, and increased by 12.73%, 12.10%, 12.63%, and 10.31% for overexpression mutants. Pathogenicity analysis showed decreased disease incidence with PgPG1 RNAi mutants and increased severity with overexpression mutants. Trypan blue staining and polygalacturonase activity assays confirmed that overexpression mutants caused more severe damage compared to wild-type and RNAi mutants. These findings indicate that PgPG1 plays a vital role in the pathogenicity of P. graminea in barley and has great potential as a pathogen target gene to develop a durable resistance variety to P. graminea.

  PublisherOA PDFDOI

• One-hour extraction-free loop-mediated isothermal amplification HPV DNA assay for point-of-care testing in Maputo, Mozambique

  Nature Communications · 2025-08-07 · 5 citations

  articleOpen access

  Human papillomavirus (HPV) is responsible for nearly all cases of cervical cancer. Affordable point-of-care DNA testing is needed for cervical cancer screening in low- and middle-income countries, where most cervical cancer cases occur. HPV DNA testing typically requires complex lab infrastructure and trained personnel. In this work, we develop a loop-mediated isothermal amplification (LAMP)-based HPV DNA test, which targets three of the most oncogenic HPV types (HPV16, HPV18, HPV45) and a cellular control and achieves analytical sensitivity comparable to gold standard methods. Our extraction-free sample preparation strategy permits adding sample lysate directly to the LAMP reaction. We utilize a low-cost benchtop heater/fluorimeter, delivering results in less than one hour. We analytically evaluate our assay with clinical samples in Houston, Texas (n = 38) and Maputo, Mozambique (n = 191). Results show 100% and 93% concordance, respectively, with a reference test widely used in low-resource settings. This sensitive and specific four-step assay can potentially expand cervical cancer screening in resource-limited settings.

  PublisherOA PDFDOI

• A Novel Homozygous Mutation in ZMYND10 Cause Primary Ciliary Dyskinesia and Female Infertility

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01 · 1 citations

  article

  Abstract Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by defective ciliary motility, typically inherited in an autosomal recessive manner. The main pathogenic mechanisms of PCD are structural or functional abnormalities of motile cilia, along with reduced generation of motile cilia(RGMC). ZMYND10 is a MYND zinc finger protein. Previous studies have reported that its functional defects can lead to PCD and multiple morphological abnormalities of the flagella (MMAF) by affecting the assembly of dynein arms. However, no association with female infertility has been reported. Case: Patient is a 34-year-old female with a clinical history of persistent cough and expectoration of yellow-green sputum for over 9 years, accompanied by anosmia, and primary infertility despite normal sexual activity for 5 years. Further examination revealed bilateral bronchiectasis on chest CT, a sputum culture positive for Pseudomonas aeruginosa infection, and a nasal nitric oxide (nNO) measurement of 6.6 nL/min. Nasal sinus CT showed bilateral chronic sinusitis. Cardiac ultrasound revealed situs inversus with mild mitral and tricuspid valve regurgitation. Chromosomal analysis showed a normal karyotype (46, XX, no significant abnormalities). We further conducted high-speed video microscopy (HSVM) on nasal cilia, which showed almost no ciliary movement. Whole exome sequencing revealed a pathogenic homozygous mutation in ZMYND10 (NM_015896.4: c.511-1G>A). Subsequent transmission electron microscopy (TEM) and immunofluorescence analysis of ciliary structural proteins revealed loss of both inner and outer dynein arms in the patient's cilia. Immunofluorescence showed a loss of DNAH5, DNALI1, and GAS8 expression, while DNAH2 expression was present. qPCR further confirmed a significant reduction in ZMYND10 mRNA expression in the patient (p<0.0001). Based on all these findings, we considered the patient to have the classic presentation of Kartagener syndrome, and the diagnosis of PCD with primary infertility was made. The patient had no acute exacerbation after active airway clearance and is actively seeking in vitro fertilization. Discussion: PCD exhibits extensive clinical heterogeneity and genetic specificity, with different gene mutations presenting diverse clinical manifestations in affected individuals. We report the first case of female infertility caused by a ZMYND10 gene mutation. The potential mechanism involves impaired assembly of the inner dynein arm monomer and outer dynein arm in the fallopian tube cilia, leading to defective ciliary motility. This study broadens the genetic spectrum of PCD in relation to female infertility and provides a theoretical basis for genetic counseling and precision medicine.

  PublisherDOI

• Transcriptome Analysis and Functional Characterization of the HvLRR_8-1 Gene Involved in Barley Resistance to Pyrenophora graminea

  Plants · 2025-07-30

  articleOpen access

  Barley leaf stripe, caused by Pyrenophora graminea (Pg), significantly reduces yields across various regions globally. Understanding the resistance mechanisms of barley to Pg is crucial for advancing disease resistance breeding efforts. In this study, two barley genotypes—highly susceptible Alexis and immune Ganpi2—were inoculated with the highly pathogenic Pg isolate QWC for 7, 14, and 18 days. The number of differentially expressed genes (DEGs) in Alexis was 1350, 1898, and 2055 at 7, 14, and 18 days, respectively, while Ganpi2 exhibited 1195, 1682, and 2225 DEGs at the same time points. Gene expression pattern analysis revealed that Alexis responded more slowly to Pg infection compared to Ganpi2. A comparative analysis identified 457 DEGs associated with Ganpi2’s immunity to Pg. Functional enrichment of these DEGs highlighted the involvement of genes related to plant-pathogen interactions and kinase activity in Pg immunity. Additionally, 20 resistance genes and 24 transcription factor genes were predicted from the 457 DEGs. Twelve candidate genes were selected for qRT-PCR verification, and the results showed that the transcriptomic data was reliable. We conducted cloning of the candidate Pg resistance gene HvLRR_8-1 by the barley cultivar Ganpi2, and the sequence analysis confirmed that the HvLRR_8-1 gene contains seven leucine-rich repeat (LRR) domains and an S_TKc domain. Subcellular localization in tobacco indicates that the HvLRR_8-1 is localized on the cell membrane. Through the functional analysis using virus-induced gene silencing, it was demonstrated that HvLRR_8-1 plays a critical role in regulating barley resistance to Pg. This study represents the first comparative transcriptome analysis of barley varieties with differing responses to Pg infection, providing that HvLRR_8-1 represents a promising candidate gene for improving durable resistance against Pg in cultivated barley.

  PublisherDOI

• Structural basis and selectivity of sulfatinib binding to FGFR and CSF-1R

  Communications Chemistry · 2024-01-03 · 13 citations

  articleOpen access

  Abstract Acquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1R T663I . This study not only sheds light on the structural basis governing sulfatinib’s FGFR/CSF-1R inhibition, but also provides valuable insights into the rational design of dual- or multi-target FGFR inhibitors with selectivity for CSF-1R and sensitivity to gatekeeper mutations.

  PublisherOA PDFDOI

• Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4

  European Journal of Medicinal Chemistry · 2024-02-28 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• Structural insights into the HDAC4–MEF2A–DNA complex and its implication in long-range transcriptional regulation

  Nucleic Acids Research · 2024-01-28 · 13 citations

  articleOpen access

  Class IIa Histone deacetylases (HDACs), including HDAC4, 5, 7 and 9, play key roles in multiple important developmental and differentiation processes. Recent studies have shown that class IIa HDACs exert their transcriptional repressive function by interacting with tissue-specific transcription factors, such as members of the myocyte enhancer factor 2 (MEF2) family of transcription factors. However, the molecular mechanism is not well understood. In this study, we determined the crystal structure of an HDAC4-MEF2A-DNA complex. This complex adopts a dumbbell-shaped overall architecture, with a 2:4:2 stoichiometry of HDAC4, MEF2A and DNA molecules. In the complex, two HDAC4 molecules form a dimer through the interaction of their glutamine-rich domain (GRD) to form the stem of the 'dumbbell'; while two MEF2A dimers and their cognate DNA molecules are bridged by the HDAC4 dimer. Our structural observations were then validated using biochemical and mutagenesis assays. Further cell-based luciferase reporter gene assays revealed that the dimerization of HDAC4 is crucial in its ability to repress the transcriptional activities of MEF2 proteins. Taken together, our findings not only provide the structural basis for the assembly of the HDAC4-MEF2A-DNA complex but also shed light on the molecular mechanism of HDAC4-mediated long-range gene regulation.

  PublisherOA PDFDOI

• P05-37 Graph attention networks using knowledge graphs, for predicting novel points of departure for brominated flame retardants

  Toxicology Letters · 2024-09-01

  article
  PublisherDOI

• Predicting miRNA–Disease Associations by Combining Graph and Hypergraph Convolutional Network

  Interdisciplinary Sciences Computational Life Sciences · 2024-01-29 · 16 citations

  article
  PublisherDOI

Recent grants

• Studying of pink1/parkin cellular pathway in Drosophila

  NIH · $1.5M · 2008–2015

• Mitochondrial DNA Quality Control and Neurodegeneration

  NIH · $1.2M · 2013–2018

• NIH Grant K08NS042580

  NIH · $853k · 2007

• NIH Grant R01NS048396

  NIH · $1.7M · 2011

• The Pink1-Parkin Pathway, Mitochondria and Parkinson's Disease

  NIH · $714k · 2008–2014

Frequent coauthors

• Yongheng Chen

  Central South University

  94 shared

• Longying Jiang

  Central South University

  61 shared

• Hudie Wei

  Xiangya Hospital Central South University

  56 shared

• Lingzhi Qu

  Central South University

  55 shared

• Shuyan Dai

  Central South University

  54 shared

• Zhuchu Chen

  Xiangya Hospital Central South University

  53 shared

• Xiaojuan Chen

  Beijing Radiation Center

  25 shared

• Lin Chen

  University of Southern California

  21 shared