About

Guo-Li Ming, M.D., Ph.D., is the Perelman Professor of Neuroscience in the Department of Neuroscience at the University of Pennsylvania's Perelman School of Medicine. His research expertise centers on the neurobiology of mental disorders, neural development, human induced pluripotent stem cells, cell signaling, and cell and molecular biology. His laboratory focuses on understanding the molecular mechanisms underlying neurodevelopment and how its dysregulation may contribute to developmental neurological disorders. The research employs a combination of experimental approaches, including molecular biology, biochemistry, mouse genetics, imaging, electrophysiology, electron microscopy, optogenetic manipulations, next-generation sequencing, and behavioral tests. The laboratory uses genetically modified mouse models and patient-derived induced pluripotent stem cell (iPSC) systems to study neuronal migration, axon and dendritic development, synapse formation, circuitry integration, neuronal plasticity, and functional regeneration of mature neurons.

Research topics

• Biology
• Neuroscience
• Cell biology
• Genetics
• Medicine
• Computer Science
• Physics
• Surgery
• Chemistry
• Oncology
• Cancer research
• Computational biology
• Immunology
• Virology
• Nanotechnology
• Zoology
• Psychology
• Psychiatry
• Internal medicine
• Pharmacology
• Biophysics
• Biochemistry

Selected publications

• Targeting G9a-m6A translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae

  UNC Libraries · 2025-05-22

  articleOpen access
  PublisherDOI

• m6A deficiency impairs hypothalamic neurogenesis of feeding-related neurons in mice and human organoids and leads to adult obesity in mice

  Cell stem cell · 2025-03-19 · 12 citations

  articleOpen access
  PublisherOA PDFDOI

• Development and Characterization of a Primary Patient Tumor Tissue-Derived Skull-Base Chordoma Organoid Model

  Journal of Neurological Surgery Part B Skull Base · 2025-02-01

  articleSenior author
  PublisherDOI

• W51. PATIENT-SPECIFIC SETD1A MUTATIONS IMPAIR NEURONAL DIFFERENTIATION AND FUNCTION IN HUMAN CORTICAL ORGANOIDS

  European Neuropsychopharmacology · 2025-10-01

  article
  PublisherDOI

• Bioengineering tools for next-generation neural organoids

  Current Opinion in Neurobiology · 2025-03-24 · 7 citations

  reviewOpen accessSenior authorCorresponding

  Human stem cell-derived neural organoids were recently introduced as powerful in vitro 3D experimental model systems that innately undergo critical steps of organogenesis in culture and exhibit molecular, cellular, and structural features similar to the fetal human nervous system. These organoids have yielded new insights into human neurodevelopment and associated disorders. However, neural organoids have some crucial limitations that arise from the loosely controlled conditions for their development, an inability to maintain their spatial orientation in culture and a lack of technologies for taking long-term measurements on their morphology and electrical activity. Here, we review recent progress in using bioengineering methods to improve neural organoid formation and analysis by leveraging microfabrication, biomaterials, 3D printing, and flexible electrodes. We discuss how the applications of each technique can help to address critical limitations with standard neural organoid models. We conclude with a perspective on future applications of bioengineered next-generation neural organoids.

  PublisherDOI

• Lack of mRNA Methylation in Schwann Cells Results in Demyelination and Regenerative Failure

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-07

  preprintOpen access

  Abstract Schwann cells are essential for peripheral nerve myelination and regeneration. N6-methyladenosine (m6A) RNA methylation, regulated by methyltransferase-like 14 (Mettl14), is a critical post-transcriptional modification, but its role in Schwann cell biology remains unclear. Using a conditional knockout (cKO) mouse model, we investigated the impact of Mettl14-mediated m6A methylation on Schwann cells. Mice born with Schwann cell-specific genetic deletion of Mettl14 developed normally but starting in young adulthood exhibited progressive motor deficits, severe demyelination, and axonal degeneration, confirmed by behavioral assessments and histological analyses. Mettl14-deficient Schwann cells displayed impaired proliferation and mitochondrial dysfunction in vitro. Following sciatic nerve injury, Mettl14 cKO mice showed defective macrophage recruitment, slowed axonal degeneration, and impaired regeneration. These findings suggest that Mettl14-mediated m6A methylation is critical for Schwann cell maintenance but not development. Given that Mettl14 cKO mice developed a demyelinating polyneuropathy, it is possible that manipulation of m6A methylation in Schwann cells is a promising therapeutic strategy targeting peripheral nerve repair and myelination.

  PublisherOA PDFDOI

• Oropouche virus disrupts neurodevelopment and is vertically transmitted

  Research Square · 2025-09-09 · 1 citations

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes

  UNC Libraries · 2025-10-17

  articleOpen access
  PublisherDOI

• Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-17

  preprintOpen accessCorresponding

  Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development. We further identified human-specific transcriptomic features of imGCs and demonstrated functional roles of human imGC-enriched expression of a family of proton-transporting vacuolar-type ATPase subtypes in development of imGCs derived from human pluripotent stem cells. Our study reveals divergent gene expression patterns but convergent biological processes in the molecular characteristics of imGCs across species, highlighting the importance of conducting independent molecular and functional analyses for adult neurogenesis in different species.

  PublisherOA PDFDOI

• CNSC-24. A CHOLINERGIC NEURON-TO-TUMOR CIRCUIT ENHANCES HUMAN GLIOBLASTOMA PROGRESSION VIA SYNAPTIC AND PARACRINE MECHANISMS

  Neuro-Oncology · 2025-11-01

  articleOpen access

  Abstract Neuronal influences on malignant brain tumor pathogenesis and progression have been increasingly recognized in the central nervous system. In glioblastoma (GBM), mainly glutamatergic inputs have been identified, and so far, they have largely been studied in the context of interspecies xenotransplantation models. We and others have recently leveraged viral tools, such as rabies virus-based retrograde tracing, to define brain-wide connectivity of GBM, which suggested the potential for GBM to receive projections from diverse neuronal subtypes, including modulatory neurons. Here, we explored the cholinergic neuron-to-glioma circuit in in vivo and all-human models to elucidate the impact of cholinergic neuronal activity on GBM biology. In mice, we leveraged electron microscopy to provide structural evidence for a basal forebrain cholinergic neuron (BFCN)-to-GBM synapse. Stimulation of BFCNs via chemogenetic approaches increased tumor cell proliferation. We further found that CHRM3 mediates the effects of BFCNs on GBM proliferation by either overexpressing CHRM3, whose specific activation increased proliferation, or knocking down CHRM3 in tumor cells, which extended mouse survival. We also developed a co-culture system employing patient-derived glioblastoma organoids and human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. In this system, we provided evidence of structural human cholinergic synaptic inputs onto GBM cells via trans-monosynaptic tracing and electron microscopy and functional synaptic interactions through the CHRM3 receptor via calcium imaging. Deep single-cell RNA sequencing of co-cultures compared to GBM monocultures further revealed shifts in tumor transcriptional profiles toward a more proliferative state, with contributions from both diffusible factors and direct contacts. Finally, pharmacological blockade of cholesterol biosynthetic pathways attenuated these effects, suggesting that lipid metabolism at least partially mediates the pro-proliferative effects of cholinergic neurons on GBM. Collectively our findings uncover a cholinergic circuit that drives GBM progression via contact-dependent and independent programs, highlighting a previously underappreciated modulatory pathway for GBM.

  PublisherOA PDFDOI

Recent grants

• Epigenetic regulation of neurogenesis

  NIH · $8.5M · 2016–2021

• Loss-of-Function Analyses of SETD1A in Human Neural Models

  NIH · $3.2M · 2021–2026

• NIH Grant R21NS095348

  NIH · $294k · 2017

• NIH Grant RF1MH123979

  NIH · $1.7M · 2024

• NIH Grant U19AI131130

  NIH · $15.7M · 2023

Frequent coauthors

• Hongjun Song

  1053 shared

• Kimberly M. Christian

  University of Pennsylvania

  169 shared

• Ki‐Jun Yoon

  Korea Advanced Institute of Science and Technology

  115 shared

• Junjie U. Guo

  Affiliated Hospital of Qingdao University

  103 shared

• Zhexing Wen

  Emory University

  100 shared

• Fadi Jacob

  Emory University

  100 shared

• Yijing Su

  96 shared

• Kurt A. Sailor

  Institut Pasteur

  84 shared

Labs

• Ming LabPI

Education

• M.D., Medicine (OBGYN)

  Tongji Medical University

  1994

• Ph.D., Biology

  University of California at San Diego

  2002