Ching Man Wai

Therapy-associated lineage plasticity in DIPG following combined CDK4/6 inhibitor, temozolomide, and radiation

Zilu Huang, Tongchao Jiang, Milagros M. Suarez Palacios, Tommy Ouyang et autres

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Multisite Assessment of Methods for Cell Preservation Upstream of Single-Cell RNA Sequencing

Fred Kolling, Jessica W. Podnar, Owen Michael Wilkins, Madolyn L. MacDonald et autres

Introduction/Objective: Single-cell RNA sequencing (scRNA-seq) resolves cell types and molecular phenotypes within heterogeneous specimens but typically requires fresh, high-quality single-cell suspensions processed immediately to preserve transcriptional profiles. This constraint complicates samples with long preparation times and prevents collection at remote sites lacking …

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Abstract 2496: In silico screening of therapeutics candidates targeting minimal residual disease in glioblastoma

Harrshavasan T. S. Congivaram, Shashwat Tripathi, Mateo Gomez, Katy McCortney et autres

Abstract Background: Glioblastoma recurrence is inevitable despite aggressive surgical resection of contrast enhancing (CE) tumor. Unlike the deep molecular characterization of CE glioblastoma, unresected infiltrating tumor, representing minimal residual disease (MRD) has not been well profiled. Increasingly, clinical trials are being conducted …

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Abstract 1150: Combining CDK4/6 inhibitor with TMZ and radiation alters cell states for synergistic responses in orthotopic DIPG models

Zilu Huang, Tongchao Jiang, Milagros M. Suarez Palacios, Tommy Ouyang et autres

Abstract Background: To develop effective therapies for DIPG at different clinical stages, we examined efficacy and mechanisms of action of a combination therapy—abemaciclib (a CDK4/6 inhibitor), temozolomide (TMZ), and radiation (XRT)—in two patient-derived orthotopic xenograft (PDOX) models derived from treatment-naïve (IBs-9119DIPG) and …

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Single-cell capture of on-ART SIV transcription reveals TGF-β–mediated metabolic control of viral latency

Romaila Abd-El-Raouf, Jakob Harrison-Gleason, Jinhee Kim, Ching Man Wai et autres

We previously demonstrated that blocking TGF-β with galunisertib, a safe, orally available small drug, reactivated latent SIV in vivo by shifting T cells toward a transitional effector phenotype. Here, we investigated the mechanisms underlying this effect using single-cell RNA sequencing, metabolic profiling, …

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STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways

Mark W. Youngblood, Shashwat Tripathi, Hinda Najem, Harrshavasan T. S. Congivaram et autres

Meningiomas are common tumors of the central nervous system that are typically treated with surgery or radiation, but lack established systemic therapies. Activation of the stimulator of interferon genes pathway with an agonist such as 8803 can trigger anti-tumor immune responses. Using …

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Machine Learning Identifies Distinct Treg-Mediated Remodeling in HFpEF Hearts Treated with Neonatal Mesenchymal Stem Cells and Their Secretome

Zhi‐Dong Ge, Jonghyeuk Han, Felipe Takaesu, Rachana Mishra et autres

Abstract Background Heart failure with preserved ejection fraction (HFpEF) remains a major therapeutic challenge due to its complex pathophysiology and pronounced heterogeneity. Regenerative approaches using neonatal mesenchymal stromal cells (nMSCs) and their secretome (SEC) have shown promise in other heart failure contexts. …

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Recreating viable YYh genotype uncovers the role of CpYYL underlying YY lethality in papaya

Jingjing Yue, Juan Liu, Qiuxia Zeng, Ching Man Wai et autres

Papaya is a trioecious species with XX females, XY males, and XYh hermaphrodites. Any combination of Y and Yh chromosomes is lethal. The gene underlying YY lethality is pivotal in the transition from stage 2 to stage 3 in sex chromosome evolution. …

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Alcohol use disorder–associated gene FNDC4 alters glutamatergic and GABAergic neurogenesis in neural organoids

Xiujuan Zhu, August J. John, Sooan Kim, Li Wang et autres

Large-cohort GWAS for alcohol use disorder (AUD) drug treatment outcomes and AUD risk have repeatedly identified genetic loci that are splicing quantitative trait loci for the fibronectin III domain containing 4 (FNDC4) gene in the brain. However, FNDC4 function in the brain …

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Spatial transcriptomic dissection of the myeloproliferative neoplasm niche uncovers mutant clone interactions and microenvironmental rewiring

Honghao Bi, Pan Wang, Ching Man Wai, Kehan Ren et autres

Abstract The development of myeloid neoplasms involves complex cell-cell communication and functional changes within the bone marrow niche. Current NGS techniques, such as scRNA-seq, capture transcriptomic changes at the single-cell level but fail to reveal cell-cell spatial context and physical interactions. To …

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DDDR-62. Dissecting cellular state alterations critical for the synergistic response and therapy resistance of the combined Abemaciclib, Temozolomide, and Radiation in DIPG PDOX models

Zilu Huang, Tongchao Jiang, Milagros Melanie Suarez Palacios, Aalaa Sanad Abdallah et autres

Abstract Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain cancer. Here, we demonstrated that combining the CDK4/6 inhibitor abemaciclib with temozolomide and radiation (the triple therapy) yields synergistic anti-tumor effects in DIPG organoids and significantly extends survival times in patient-derived …

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IMMU-07. Synergistic STING activation in meningioma neoplastic and immune populations triggers programmed necrosis and modulates the collagen-rich immunosuppressive microenvironment

Mark W. Youngblood, Shashwat Tripathi, Hinda Najem, Harrshavasan T. S. Congivaram et autres

Abstract Despite recent progress in elucidating the molecular events underlying meningioma aggressiveness, there remain no established adjuvant therapies for tumors that are intractable to surgery and radiation. Using integrated approaches of single-cell RNA/ATAC-seq, spatial multiprotein immunofluorescence, and bulk RNA-seq and methylation profiling, …

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