About

The Lu Lab is located in the Yale Stem Cell Center in the Amistad Building on the Yale School of Medicine campus. We are proud members of the Yale Stem Cell Center and Department of Genetics. We are also members of Yale Cancer Center, Yale Center of RNA Science and Medicine, and Yale Cooperative Center of Excellence in Hematology. We are a bunch of science lovers. We value challenging our minds to think out of the box, keeping our curiosity, critical analysis of experimentation and data, enjoying the journey toward discovery, and appreciating each other's friendship.

Research topics

• Biology
• Immunology
• Biochemistry
• Cancer research
• Genetics
• Pharmacology
• Internal medicine
• Cell biology
• Medicine

Selected publications

• The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option

  Gut Microbes · 2026-01-07

  articleOpen access

  = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.

  PublisherDOI

• Evaluation of GFM1 mutations pathogenicity through in silico tools, RNA sequencing and mitophagy pahtway in GFM1 knockout cells

  International Journal of Biological Macromolecules · 2025-02-12 · 5 citations

  articleOpen accessSenior authorCorresponding

  GFM1 is a nuclear gene that plays a role in mitochondrial function. In recent decades, various homozygous and compound heterozygous mutations have been identified, leading to significant health issues in patients and often resulting in early death. There is a few experimental research on this gene, particularly regarding its pathogenicity through in silico methods and RNA sequencing and experimental validation in GFM1 knockout cells. This study aims to explore how high-risk pathogenic variants affect protein stability and function using a comprehensive bioinformatics approach. Analyses with Align-GVGD, PolyPhen-2, MupRo, and SIFT indicated that most variants are likely to be highly pathogenic and destabilize the protein structure. The variants were consistently classified as high-risk by Align-GVGD and were deemed "probably damaging" or "possibly damaging" by PolyPhen-2. MupRo analysis suggested a reduction in protein stability, while SIFT indicated functional impacts for all variants. Further analysis with MetaRNN and structural assessments showed that these variants affect protein size, charge, and hydrophobicity, which may disrupt inter-domain interactions and hinder protein function. Differential gene expression analysis in GFM1 knockout HK2 and 293 T cells revealed significant changes in gene expression, particularly in areas related to translation, mitochondrial function, and cellular responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the affected genes are linked to neurodegenerative diseases, cancer, and various signaling pathways. GFM1 knockout cells displayed notable pathway changes, including those related to oxidative phosphorylation and neurodegenerative diseases (e.g., Parkinson's, Alzheimer's, Huntington's). Upregulation of mitochondrial electron transport chain components (COX17, NDUFB1, ATP5MC1) suggests a compensatory mechanism in response to impaired mitochondrial function. Disruptions in proteostasis and protein synthesis were highlighted by dysregulated proteasome and ribosomal pathways. Markers of mitophagy, such as increased HSP90 and decreased TOMM20 levels, along with changes in PINK1 protein, emphasize GFM1's involvement in mitophagy. Protein-protein interaction analysis connected GFM1 to key mitophagy proteins (e.g., OPTN, Park2/Parkin). Functional experiments confirmed increased mitophagy, indicating a protective response. These results highlight the negative impact of high-risk pathogenic variants on protein stability and cellular function, shedding light on their potential roles in disease progression. This study offers valuable insights into the pathogenic mechanisms linked to GFM1 mutations, underscoring its critical role in mitochondrial function and cellular balance. The findings highlight the gene's involvement in mitophagy, oxidative phosphorylation, and neurodegenerative pathways, laying the groundwork for future research into therapeutic approaches targeting GFM1-related dysfunctions.

  PublisherDOI

• Silencing LINC01547 induces hepatocellular carcinoma cell apoptosis and metastasis inhibition via the ADAR1/FAK and miR-146b-5p/RAC1 axes

  APOPTOSIS · 2025-02-04 · 2 citations

  articleCorresponding
  PublisherDOI

• Sugar coats shield immunogenic RNA modification:A new function for RNA glycosylation

  Molecular Cell · 2025-10-01

  articleSenior author
  PublisherDOI

• Corrigendum to “Evaluation of GFM1 mutations pathogenicity through in silico tools, RNA sequencing and mitophagy pathway in GFM1 knockout cells” [Int. J. Biol. Macromol. Volume 304, Part 2, April 2025, 140970]

  International Journal of Biological Macromolecules · 2025-07-01

  erratumSenior authorCorresponding
  PublisherDOI

• ASTRO: Automated Spatial Whole-Transcriptome RNA-Expression Workflow

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-27 · 1 citations

  preprintOpen access

  Abstract Motivation Despite significant advances in spatial transcriptomics, the analysis of formalin-fixed paraffin-embedded (FFPE) tissues, which constitute most clinically available samples, remains challenging. Additionally, capturing both coding and noncoding RNAs in a spatial context poses significant challenges. We recently introduced Patho-DBiT, a technology designed to address these unmet needs. However, the marked differences between Patho-DBiT and existing spatial transcriptomics protocols necessitate specialized computational tools for comprehensive whole-transcriptome analysis in FFPE samples. Results Here, we present ASTRO, an automated pipeline developed to process spatial transcriptomics data. In addition to supporting standard datasets, ASTRO is optimized for whole-transcriptome analyses of FFPE samples, enabling the detection of various RNA species, including non-coding RNAs such as miRNAs. To compensate for the reduced RNA quality in FFPE tissues, ASTRO incorporates a specialized filtering step and optimizes spatial barcode calling, increasing the mapping rate. These optimizations allow ASTRO to spatially quantify coding and non-coding RNA species in the entire transcriptome and achieve robust performance in FFPE samples. Availability Codes are available at GitHub ( https://github.com/gersteinlab/ASTRO ).

  PublisherDOI

• Rett syndrome: Pathogenicity and regulation of MECP2 (human) and Mecp2 (mouse) genes and their protein products through various molecular mechanisms

  Mutation Research/Reviews in Mutation Research · 2025-07-01

  reviewSenior authorCorresponding
  PublisherDOI

• Global trends and frontiers in iNKT cells: a bibliometric and visualized analysis

  Frontiers in Immunology · 2025-07-08 · 1 citations

  articleOpen accessSenior author

  Background: Invariant natural killer T (iNKT) cells are an unconventional lymphocyte subset that has garnered increasing attention due to their shared features with both natural killer cells and conventional T cells, as well as their unique dual immunological functions. In this study, we conducted a comprehensive bibliometric analysis to trace the evolution of research in the iNKT cell field, identify emerging trends, and highlight current research hotspots and frontier directions. Methods: We performed a literature search in the Web of Science Core Collection database to retrieve all publications related to iNKT cells published to December 31, 2024. We then used the visualization tools CiteSpace and VOSviewer to conduct a bibliometric analysis of the retrieved data. Results: We identified 2,579 relevant publications authored by 12,108 individuals from 2,218 institutions across 70 countries. These publications appeared in 540 journals and collectively cited 60,342 references from 4,322 different journals. The publication volume in the iNKT cell field has significantly increased since 2008, peaking at 151 articles in 2018. This surge highlights the sharp rise of research interest in this area. The United States led in publication output within this field. Among the journals, the Journal of Immunology was the most prolific and also ranked first in total citations. Besra was the most published author, while Bendelac's research was highly influential. Research on iNKT cells is undergoing a paradigm shift from mechanistic exploration to clinical application. Conclusions: Our bibliometric analysis delineates the thematic evolution within the iNKT cell research landscape. Future investigations will converge on several pivotal frontiers, including improving the tumor microenvironment, reprogramming the functional activity of iNKT cells within tumors, and advancing engineered immunotherapies. Additionally, strategies to engineer iNKT cells for more targeted and effective therapeutic interventions are likely to gain momentum, as researchers aim to overcome the current limitations in the field and transition from basic mechanistic studies to more impactful clinical applications.

  PublisherDOI

• A1 BACTERIAL LYSOPHOSPHATIDYLCHOLINE (LPC) AND LYSOPHOSPHATIDIC ACID (LPA) INDUCE VISCERAL HYPERSENSITIVITY THROUGH TRANSIENT RECEPTOR POTENTIAL CANONICAL 5 (TRPC5) AND LYSOPHOSPHATIDIC ACID RECEPTOR 1 (LPAR1) AND 3 (LPAR3) DEPENDENT-MECHANISMS

  Journal of the Canadian Association of Gastroenterology · 2025-02-01

  articleOpen access

  Abstract Background Abdominal pain is the key symptom in Irritable Bowel Syndrome (IBS). Its pathophysiology is not fully understood, but low-grade inflammation and gut microbiota-diet interactions have been implicated. LPC and LPA are phospholipids generated by inflammatory processes in mammals, which are known to induce neurogenic pain through multiple channels and G-protein-coupled receptors. It is unknown whether bacteria can produce LPC/LPA and through which pathways they signal to the host. Aims To investigate whether bacterial LPC and LPA induce visceral hypersensitivity and identify the underlying mechanisms. Methods Germ-free NIH Swiss and Swiss Webster mice (n=117) were colonized for 5 weeks with fecal microbiota from IBS patients with either low or high fecal LPC/LPA levels, or microbiota from healthy controls. The mice were fed either regular chow or a diet enriched with phosphatidylcholine (PC) (2g/kg) a precursor of LPC and LPA. Visceral sensitivity was assessed by visceromotor responses (VMRs) to colorectal distension. Dorsal root ganglion (DRG) neurons from C57BL/6 mice were pretreated with a TRPC5 inhibitor (AC1903; 30 μM), an LPAR1 antagonist (AM095; 10 μM), or an LPAR1 and LPAR3 antagonist (Ki16425; 10 μM) or their vehicle (0.1% DMSO), and then treated with LPC (10 μM) or LPA (10 μM), respectively. Calcium mobilization was measured by a Cytation C10 imaging reader using a fluorescent probe Fluo-4 (1 mM). C57BL/6 mice received intracolonic infusion with a vehicle or a mix of LPC (600 μM) /LPA (25 μM), one group of mice was pretreated with AC1903 (30 μM) and Ki16425 (10 μM) prior to LPC/LPA administration, CRD was performed 90 minutes later. Results Mice with fecal microbiota from IBS patients with high fecal LPC/LPA displayed visceral hypersensitivity compared to mice with microbiota from healthy controls or from patients with low fecal LPC/LPA. These increased responses were seen only in mice fed PC-enriched diet, but not with regular chow. Both LPC and LPA administration increased the percentage of responding DRG neurons compared to the vehicle. The pretreatment with AC1903, AM095 or Ki16425 decreased the percentage of responding neurons when treated with LPC or LPA, respectively, compared to the vehicle. Intracolonic administration of LPC and LPA induced a significant increase in visceral sensitivity compared to the vehicle-treated mice. This increase was prevented in mice pretreated with an intracolonic injection of AC1903 and Ki16425. Conclusions Bacterial LPC and LPA induce neuronal activation and visceral hypersensitivity through TRPC5 and LPAR1/LPAR3-dependent mechanisms, respectively. Funding Agencies CIHRWeston Family Foundation

  PublisherDOI

• Spatially Exploring RNA Biology in Archival Formalin-Fixed Paraffin-Embedded Tissues

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-08 · 16 citations

  preprintOpen accessCorresponding

  Abstract Spatial transcriptomics has emerged as a powerful tool for dissecting spatial cellular heterogeneity but as of today is largely limited to gene expression analysis. Yet, the life of RNA molecules is multifaceted and dynamic, requiring spatial profiling of different RNA species throughout the life cycle to delve into the intricate RNA biology in complex tissues. Human disease-relevant tissues are commonly preserved as formalin-fixed and paraffin-embedded (FFPE) blocks, representing an important resource for human tissue specimens. The capability to spatially explore RNA biology in FFPE tissues holds transformative potential for human biology research and clinical histopathology. Here, we present Patho-DBiT combining in situ polyadenylation and deterministic barcoding for spatial full coverage transcriptome sequencing, tailored for probing the diverse landscape of RNA species even in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for five years. Furthermore, genome-wide single nucleotide RNA variants can be captured to distinguish different malignant clones from non-malignant cells in human lymphomas. Patho-DBiT also maps microRNA-mRNA regulatory networks and RNA splicing dynamics, decoding their roles in spatial tumorigenesis trajectory. High resolution Patho-DBiT at the cellular level reveals a spatial neighborhood and traces the spatiotemporal kinetics driving tumor progression. Patho-DBiT stands poised as a valuable platform to unravel rich RNA biology in FFPE tissues to study human tissue biology and aid in clinical pathology evaluation.

  PublisherOA PDFDOI

Recent grants

• Quantitative Modeling of MicroRNA:Target Interactions in Cell Fate Transition

  NIH · $2.2M · 2016–2021

• Novel Bioinformatics Tools for Quantitative Prediction of Primary MicroRNA Processing

  NIH · $1.8M · 2020–2025

• Novel Approaches to Mammalian MicroRNA Target Prediction

  NIH · $2.4M · 2012–2017

• The role of microRNAs in leukemic initiation and maintenance

  NIH · $1.7M · 2011–2017

• CRISPR-based Enhanced Molecular Chipper Technology for Identifying Functional Noncoding Elements in Cancer

  NIH · $1.2M · 2018–2022

Frequent coauthors

• Todd R. Golub

  Broad Institute

  104 shared

• Přemysl Berčík

  McMaster University

  66 shared

• Jijun Cheng

  Yale University

  62 shared

• Stephen M. Collins

  Population Health Research Institute

  58 shared

• Shangqin Guo

  Yale Cancer Center

  57 shared

• Elena F. Verdú

  McMaster University

  51 shared

• Giada De Palma

  Digestive Health Research Institute

  44 shared

• Rong Fan

  43 shared

Labs

• Yale Lu LabPI

Education

• PhD, Biochemistry

  Boston University

  2003

Awards & honors

• Yale Ventures