About

Dr. Yingqun Huang is a Professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. She received her undergraduate and medical degrees from Fudan University School of Medicine in 1988 and her Ph.D. in Biomedical Sciences from the University of Connecticut Health Center in 1997. Her postdoctoral studies included work with Dr. Gordon Carmichael at the University of Connecticut Health Center and Dr. Joan Steitz at Yale University School of Medicine. Her research centers on understanding the mechanisms underlying metabolic disorders such as obesity, diabetes, and infertility, as well as reproductive tract tumors. Using cell and mouse models, her lab generates insights into disease pathogenesis with the goal of improving human health. She has made significant contributions to the field of noncoding RNAs, demonstrating the potential of long noncoding RNA H19 and microRNA let-7 as targets or therapeutics for uterine fibroids, ovarian and endometrial cancers, and type-2 diabetes. Her recent research extends to the epigenetic mechanisms involving TET3 in metabolic diseases and cancer, including regulation of hepatic glucose production, liver fibrosis, insulin sensitivity, feeding behaviors, and development of therapeutic approaches for various disorders. Dr. Huang has published extensively in high-impact journals and is recognized for her dedication to teaching and mentoring, having trained many medical fellows, postdoctoral associates, and graduate students. She has served as Director of the Molecular Biology Core Training Laboratory for the Yale Women’s Reproductive Health Research program and received the Harold Behrman Teaching Award in 2013.

Research topics

• Biology
• Cell biology
• Cancer research
• Endocrinology
• Genetics
• Medicine
• Computer Science
• Computer Security
• Mathematics
• Chemistry
• Bioinformatics
• Physics
• Engineering
• Electrical engineering
• Internal medicine

Selected publications

• TET3 is a common epigenetic immunomodulator of pathogenic macrophages

  Journal of Clinical Investigation · 2025-08-12 · 5 citations

  articleOpen accessSenior author

  Through a combination of single-cell/single-nucleus RNA-Seq (sc/snRNA-Seq) data analysis, immunohistochemistry, and primary macrophage studies, we have identified pathogenic macrophages characterized by Tet methylcytosine dioxygenase 3 (TET3) overexpression (Toe-Macs) in 3 major human diseases associated with chronic inflammation: metabolic dysfunction-associated steatohepatitis (MASH), non-small cell lung cancer (NSCLC), and endometriosis. These macrophages are induced by common factors present in the disease microenvironment (DME). Crucially, the universal reliance on TET3 overexpression among these macrophages enabled their selective elimination as a single population, irrespective of heterogeneity in other molecular markers. In mice, depleting these macrophages via myeloid-specific Tet3 KO markedly mitigated disease progression, and the therapeutic effects were recapitulated pharmacologically using a TET3-specific small-molecule degrader. Through an unexpected mode of action, TET3 epigenetically regulated the expression of multiple genes key to the generation and maintenance of an inflammatory/immunosuppressive DME. We propose that Toe-Macs are a unifying feature of pathogenic macrophages that could be therapeutically targeted to treat MASH, NSCLC, endometriosis, and potentially other chronic inflammatory diseases.

  PublisherOA PDFDOI

• Regulated circRNA nuclear export in neuronal differentiation

  Trends in Cell Biology · 2024-07-03 · 2 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Ablation Study of Diffusion Model with Transformer Backbone for Low-count PET Denoising

  2024-09-25

  articleOpen access1st authorCorresponding

  Diffusion models (DM) built from a hierarchy of denoising autoencoders have achieved remarkable progress in image generation, and are increasingly influential in the field of image restoration (IR) tasks. In the meantime, its backbone of autoencoders also evolved from UNet to vision transformer, e.g. Restormer. Therefore, it is important to disentangle the contribution of backbone networks and the additional generative learning scheme. Notably, DM shows varied performance across IR tasks, and the performance of recent advanced transformer-based DM on PET denoising is under-explored. In this study, we further raise an intuitive question, “{if we have a sufficiently powerful backbone, whether DM can be a general add-on generative learning scheme to further boost PET denoising}”. Specifically, we investigate one of the best-in-class IR models, i.e., DiffIR, which is a latent DM based on the Restormer backbone. We provide a qualitative and quantitative comparison with UNet, SR3 (UNet+pixel DM), and Restormer, on the 25% low dose ${}^{18}\mathrm{F-FDG}$ whole-body PET denoising task, aiming to identify the best practices. We trained and tested on 93 and 12 subjects, and each subject has 644 slices. It appears that Restormer outperforms UNet in terms of PSNR and MSE. However, additional latent DM over Restormer does not contribute to better MSE, SSIM, or PSNR in our task, which is even inferior to the conventional UNet. In addition, SR3 with pixel space DM is not stable to synthesize satisfactory results. The results are consistent with the natural image super-resolution tasks, which also suffer from limited spatial information. A possible reason would be the denoising iteration at latent feature space cannot well support detailed structure and texture restoration. This issue is more crucial in the IR tasks taking inputs with limited details, e.g., SR and PET denoising.

  PublisherOA PDFDOI

• Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α

  Diabetologia · 2024-01-13 · 9 citations

  articleOpen accessSenior author

  AIM/HYPOTHESIS: The peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) plays a critical role in the maintenance of glucose, lipid and energy homeostasis by orchestrating metabolic programs in multiple tissues in response to environmental cues. In skeletal muscles, PGC-1α dysregulation has been associated with insulin resistance and type 2 diabetes but the underlying mechanisms have remained elusive. This research aims to understand the role of TET3, a member of the ten-eleven translocation (TET) family dioxygenases, in PGC-1α dysregulation in skeletal muscles in obesity and diabetes. METHODS: TET expression levels in skeletal muscles were analysed in humans with or without type 2 diabetes, as well as in mouse models of high-fat diet (HFD)-induced or genetically induced (ob/ob) obesity/diabetes. Muscle-specific Tet3 knockout (mKD) mice were generated to study TET3's role in muscle insulin sensitivity. Genome-wide expression profiling (RNA-seq) of muscle tissues from wild-type (WT) and mKD mice was performed to mine deeper insights into TET3-mediated regulation of muscle insulin sensitivity. The correlation between PGC-1α and TET3 expression levels was investigated using muscle tissues and in vitro-derived myotubes. PGC-1α phosphorylation and degradation were analysed using in vitro assays. RESULTS: TET3 expression was elevated in skeletal muscles of humans with type 2 diabetes and in HFD-fed and ob/ob mice compared with healthy controls. mKD mice exhibited enhanced glucose tolerance, insulin sensitivity and resilience to HFD-induced insulin resistance. Pathway analysis of RNA-seq identified 'Mitochondrial Function' and 'PPARα Pathway' to be among the top biological processes regulated by TET3. We observed higher PGC-1α levels (~25%) in muscles of mKD mice vs WT mice, and lower PGC-1α protein levels (~25-60%) in HFD-fed or ob/ob mice compared with their control counterparts. In human and murine myotubes, increased PGC-1α levels following TET3 knockdown contributed to improved mitochondrial respiration and insulin sensitivity. TET3 formed a complex with PGC-1α and interfered with its phosphorylation, leading to its destabilisation. CONCLUSIONS/INTERPRETATION: Our results demonstrate an essential role for TET3 in the regulation of skeletal muscle insulin sensitivity and suggest that TET3 may be used as a potential therapeutic target for the metabolic syndrome. DATA AVAILABILITY: Sequences are available from the Gene Expression Omnibus ( https://www.ncbi.nlm.nih.gov/geo/ ) with accession number of GSE224042.

  PublisherOA PDFDOI

• TET3 Renders Pathogenic Macrophages Vulnerable to Targeted Elimination

  SSRN Electronic Journal · 2024-01-01

  preprintOpen accessSenior author
  PublisherDOI

• TET3-overexpressing macrophages promote endometriosis

  Journal of Clinical Investigation · 2024-08-14 · 24 citations

  articleOpen accessSenior author

  Endometriosis is a debilitating, chronic inflammatory disease affecting approximately 10% of reproductive-age women worldwide with no cure. While macrophages have been intrinsically linked to the pathophysiology of endometriosis, targeting them therapeutically has been extremely challenging due to their high heterogeneity and because these disease-associated macrophages (DAMs) can be either pathogenic or protective. Here, we report identification of pathogenic macrophages characterized by TET3 overexpression in human endometriosis lesions. We show that factors from the disease microenvironment upregulated TET3 expression, transforming macrophages into pathogenic DAMs. TET3 overexpression stimulated proinflammatory cytokine production via a feedback mechanism involving inhibition of let-7 miRNA expression. Remarkably, these cells relied on TET3 overexpression for survival and hence were vulnerable to TET3 knockdown. We demonstrated that Bobcat339, a synthetic cytosine derivative, triggered TET3 degradation in both human and mouse macrophages. This degradation was dependent on a von Hippel-Lindau (VHL) E3 ubiquitin ligase whose expression was also upregulated in TET3-overexpressing macrophages. Furthermore, depleting TET3-overexpressing macrophages either through myeloid-specific Tet3 ablation or using Bobcat339 strongly inhibited endometriosis progression in mice. Our results defined TET3-overexpressing macrophages as key pathogenic contributors to and attractive therapeutic targets for endometriosis. Our findings may also be applicable to other chronic inflammatory diseases where DAMs have important roles.

  PublisherOA PDFDOI

• A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model

  Proceedings of the National Academy of Sciences · 2023-04-10 · 20 citations

  articleOpen accessSenior author

  Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3 , which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

  PublisherDOI

• Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production

  Molecular Metabolism · 2023-10-27 · 22 citations

  articleOpen accessSenior authorCorresponding

  FAS-mediated apoptosis of hepatocytes and aberrant TGF-β signaling are major drivers of liver fibrosis. Decreased miRNA let-7 expression in the livers of patients and animals with fibrosis suggests a mechanistic link of let-7 to hepatic fibrogenesis. Using transient transfection we tested the effects of let-7 overexpression and TET3 siRNA knockdown on FAS and TGF-β1 expression and FAS-mediated apoptosis in human and mouse primary hepatocytes. We assessed the therapeutic activity of let-7 miRNA delivered via adeno-associated viral vectors in mouse models of carbon tetrachloride (CCl4)-induced and bile duct ligation (BDL)-induced liver fibrosis. Let-7 decreased TGF-β1 production from hepatocytes through a negative feedback loop involving TET3. On the other hand, let-7 post-transcriptionally inhibits FAS expression, thereby suppressing hepatocyte apoptosis. Hepatic-specific delivery of let-7 miRNA mitigated liver fibrosis in both CCl4 and BDL mouse models. Let-7 is a crucial node in the signaling networks that govern liver fibrosis progression. Let-7 and/or its derivatives may be used as therapeutic agents for liver fibrosis.

  PublisherDOI

• Identification and Comparative Analysis of the miRNAs in Gonads of High-altitude Species, Batrachuperus tibetanus

  Russian Journal of Bioorganic Chemistry · 2022-12-01

  article

  MicroRNAs (miRNAs) are a kind of small non-coding RNA molecules that regulate gene expression by targeting mRNA and play critical roles involved various life processes of organisms. Batrachuperus tibetanus (B. tibetanus) as an endangered amphibian species of salamander endemic to China, has attracted much attention because of its value of studying paleontology evolutionary history and decreasing population size. Until now, research in gonadal miRNA of B. tibetanus have not been reported. In this study, RNA sequencing technology was used to screen miRNAs based on the construction of two cDNA libraries from adult testis and ovary tissues of B. tibetanus, respectively. Totally, 15 481 068 and 15 929 246 raw reads were yielded in testis and ovary, respectively, representing five known and 88 novel miRNAs. Among all these identified miRNA, 54 differentially expressed miRNAs were found between testis and ovary of B. tibetanus containing 25 up-regulated as well as 29 down-regulated miRNAs. Ten miRNAs were randomly chosen to verify their expression by using stem-loop qRT-PCR indicating the reliability and accuracy of sequenced data. Additionally, further analysis of target mRNAs of differentially expressed miRNAs reveals that they were mainly involved in cellular processes, reproduction and reproductive process related GO terms. Our current result is the first to perform the identification, characterization, differential expression and functional analysis of gonadal miRNAs both in testis and ovary of B. tibetanus, which also provide a valuable reference to enhance the resource protection of stream salamander species.

  PublisherDOI

• TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons

  Journal of Clinical Investigation · 2022-10-02 · 25 citations

  articleOpen accessSenior authorCorresponding

  The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.

  PublisherOA PDFDOI

Recent grants

• H19 Long Noncoding RNA in Hepatic Gluconeogenesis Regulation

  NIH · $1.2M · 2018–2022

Frequent coauthors

• Wei Ma

  46 shared

• Jie Xu

  Second Affiliated Hospital of Fujian Medical University

  33 shared

• Chong Qiao

  Chengdu Institute of Biology

  32 shared

• Jing Ma

  30 shared

• Hugh S. Taylor

  Yale University

  24 shared

• Da Li

  National Health and Family Planning Commission

  23 shared

• Jichun Zhou

  22 shared

• Lei Yan

  20 shared

Labs

• Division of Reproductive SciencesPI

Education

• M.D.

  Fudan University School of Medicine

  1988

• Ph.D., Biomedical Sciences

  Fudan University School of Medicine

Awards & honors

• Harold Behrman Teaching Award (2013)