Bachelor of Science, Fudan University (2011)
Ph.D., University of Connecticut Health Center & The Jackson Laboratory for Genomic Medicine, Genetics and Genome Science (2019)
Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales. This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.
View details for DOI 10.2337/db19-0592
View details for PubMedID 32366680
Over the past few decades, most attention to Chinese Cordyceps-associated endogenous microorganism was focused on the fungal community that creates critical bioactive components. Bacterial community associated with Chinese Cordyceps has been previously described; however, most studies were only presenting direct comparisons in the Chinese Cordyceps and its microenvironments. In the current study, our objectives were to reveal the bacterial community structure composition and predict their function.We collected samples of Chinese Cordyceps from five sites located in the Qinghai-Tibet Plateau and used a high throughput sequencing method to compare Chinese Cordyceps-associated bacterial community composition and diversity quantitatively across sites. The results indicated that for the Chinese Cordyceps-associated bacterial community there is no single core microbiome, which was dominated by the both Proteobacteria and Actinobacteria. Predictive functional profiling suggested a location specific function pattern for Chinese Cordyceps and bacteria in the external mycelial cortices involved in the biosynthesis of active constituents.This study is firstly used high throughput sequencing method to compare the bacterial communities inhabiting Chinese Cordyceps and its microhabitat and to reveal composition functional capabilities of the bacteria, which will accelerate the study of the functions of bacterial communities in the micro-ecological system of Chinese Cordyceps.
View details for DOI 10.1186/s12866-019-1472-0
View details for Web of Science ID 000468899100003
View details for PubMedID 31122191
View details for PubMedCentralID PMC6533680
Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2Dbetter, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.
View details for DOI 10.1038/s41586-019-1236-x
View details for PubMedID 31142858
Estrogen (E2) modulates a wide range of neural functions such as spine formation, synaptic plasticity, and neurotransmission in the hippocampus. Dendritic spines and synapse numbers in hippocampal neurons of female rats cyclically fluctuate across the estrous cycle, but the key genes responsible for these fluctuations are still unknown. In order to address this question, we explore the hippocampal transcriptome via RNA-sequencing (RNA-seq) at the proestrus (PE) and estrus (ES) stages in female rats. At standard fold-change selection criteria, 37 differentially expressed genes (DEGs) were found in PE vs. ES groups (FDR adjusted p-value (q)<0.05). The transcriptional changes identified by RNA-seq were confirmed by quantitative real-time PCR. To gain insight into the function of the DEGs, the E2-regulated genes were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG). Based on GO and KEGG pathways, the identified DEGs of PE vs. ES stages are involved in extracellular matrix formation, regulation of actin cytoskeleton, oxidative stress, neuroprotection, immune system, oligodendrocyte maturation and myelination, signal transduction pathways, growth factor signaling, retinoid signaling, aging, cellular process, metabolism and transport. The profiles of the gene expression in the hippocampus identified at the PE vs. ES stages were compared with the gene expression profiles in ovariectomized (OVX) rats receiving E2 replacement via RNA-seq and qPCR. The profiles of gene expression between the OVX+E2 and the estrous cycle were different and the possible causes were discussed.
View details for DOI 10.1080/07435800.2019.1674868
View details for PubMedID 31608702
Regressing an outcome or dependent variable onto a set of input or independent variables allows the analyst to measure associations between the two so that changes in the outcome can be described by and predicted by changes in the inputs. While there are many ways of doing this in classical statistics, where the dependent variable has certain properties (e.g., a scalar, survival time, count), little progress on regression where the dependent variable are microbiome taxa counts has been made that do not impose extremely strict conditions on the data. In this paper, we propose and apply a new regression model combining the Dirichlet-multinomial distribution with recursive partitioning providing a fully non-parametric regression model. This model, called DM-RPart, is applied to cytokine data and microbiome taxa count data and is applicable to any microbiome taxa count/metadata, is automatically fit, and intuitively interpretable. This is a model which can be applied to any microbiome or other compositional data and software (R package HMP) available through the R CRAN website.
View details for DOI 10.1038/s41598-019-56397-9
View details for PubMedID 31882682
View details for PubMedCentralID PMC6934614
Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome. Young, middle-aged, and aged caloric restricted (CR) and ad lib fed (AL) mice were examined after a sublethal flu infection. All mice lost 10-20% body weight and, as expected for these early time points, losses were similar at different ages and between diet groups. Cytokine and chemokine levels were also similar with the notable exception of IL-1?, which rose more than fivefold in aged AL mouse serum, while it remained unchanged in aged CR serum. Fecal microbiome phyla abundance profiles were similar in young, middle-aged, and aged AL mice at baseline and at 4?days post flu infection, while increases in Proteobacteria were evident at 7?days post flu infection in all three age groups. CR mice, compared to AL mice in each age group, had increased abundance of Proteobacteria and Verrucomicrobia at all time points. Interestingly, principal coordinate analysis determined that diet exerts a greater effect on the microbiome than age or flu infection. Percentage body weight loss correlated with the relative abundance of Proteobacteria regardless of age, suggesting flu pathogenicity is related to Proteobacteria abundance. Further, several microbial Operational Taxonomic Units from the Bacteroidetes phyla correlated with serum chemokine/cytokines regardless of both diet and age suggesting an interplay between flu-induced systemic inflammation and gut microbiota. These exploratory studies highlight the impact of caloric restriction on fecal microbiome in both young and aged animals, as well as the many complex relationships between flu responses and gut microbiota. Thus, these preliminary studies provide the necessary groundwork to examine how gut microbiota alterations may be leveraged to influence declining immune responses with aging.
View details for DOI 10.3389/fimmu.2017.01164
View details for Web of Science ID 000411178700001
View details for PubMedID 28979265
View details for PubMedCentralID PMC5611400
Chronic viral infections (e.g., HIV, HBV, HCV) represent a significant source of morbidity and mortality with over 500 million people infected worldwide. Dendritic cells (DCs) and macrophages are key cell types for productive viral replication and persistent systemic infection. We demonstrate that the plant virus cowpea mosaic virus (CPMV) displays tropism for such antigen presenting cells in both mice and humans, thus making it an ideal candidate for targeted drug delivery toward viral infections. Furthermore, we show inhibition of a key host protein for viral infection, site-1 protease (S1P), using the small molecule PF-429242 in the model pathogen arenavirus lymphocytic choriomeningitis virus (LCMV) limits viral growth. By packaging PF-429242 in CPMV, we are able to control drug release and efficiently deliver the drug. This sets the groundwork for utilizing the natural tropism of CPMV for a therapeutic approach that specifically targets cell types most commonly subverted by chronic viruses.
View details for DOI 10.1021/acsbiomaterials.5b00344
View details for Web of Science ID 000369348500001
View details for PubMedID 27280157
View details for PubMedCentralID PMC4894745
Langerhans cell histiocytosis (LCH) carries a prognosis, which ranges from benign to potentially fatal. There is currently little framework to decipher metrics, which predict the benign versus aggressive nature of LCH. We wanted to determine whether molluscum contagiosum virus (MCV) DNA could be isolated from a cutaneous lesion, demonstrating Langerhans cell hyperplasia resembling LCH in a patient with both. Polymerase chain reaction on biopsy-proven MCV and the hyperplastic lesion has been performed. Two specific regions within the MCV genome were detected from both biopsies. The authors report our findings and suggest that some MCV can produce histological lesions resembling LCH, similar to the literature on scabies mimicking LCH. Efforts to find a reactive "driver" in LCH may significantly inform the clinical scenario.
View details for DOI 10.1097/DAD.0000000000000201
View details for PubMedID 25140667
View details for PubMedCentralID PMC4334759
Jatropha curcas L. is a highly drought and salt tolerant plant species that is typically used as a traditional folk medicine and biofuel crop in many countries. Understanding the molecular mechanisms that underlie the response to various abiotic environmental stimuli, especially to drought and salt stresses, in J. curcas could be important to crop improvement efforts. In this study, we cloned and characterized the gene for a late embryogenesis abundant (LEA) protein from J. curcas that we designated JcLEA. Sequence analyses showed that the JcLEA protein belongs to group 5, a subgroup of the LEA protein family. In young seedlings, expression of JcLEA is significantly induced by abscisic acid (ABA), dehydration, and salt stress. Subcellular localization analysis shows that that JcLEA protein is distributed in both the nucleus and cytoplasm. Moreover, based on growth status and physiological indices, the overexpression of JcLEA in transgenic Arabidopsis plants conferred increased resistance to both drought and salt stresses compared to the WT. Our data suggests that the group 5 JcLEA protein contributes to drought and salt stress tolerance in plants. Thus, JcLEA is a potential candidate gene for plant genetic modification.
View details for DOI 10.1371/journal.pone.0083056
View details for Web of Science ID 000329325200034
View details for PubMedID 24391737
View details for PubMedCentralID PMC3877014
Lymphocytic choriomeningitis virus (LCMV) is a common infection of rodents first identified over eighty years ago in St. Louis, MO, U.S.A. It is best known for its application in immunological studies. The history of LCMV closely correlates with the development of modern immunology. With the use of LCMV as a model pathogen several key concepts have emerged: Major Histocompatibility Complex (MHC) restriction, T cell memory, persistent infections, T cell exhaustion and the key role of immune pathology in disease. Given the phenomenal infrastructure within this field (e.g., defined immunodominant and subdominant epitopes to all T cell receptor specificities as well as the cognate tetramers for enumeration in vivo) the study of LCMV remains an active and productive platform for biological research across the globe to this day. Here we present a historical primer that highlights several breakthroughs since the discovery of LCMV. Next, we highlight current research in the field and conclude with our predictions for future directions in the remarkable field of LCMV research.
View details for DOI 10.3390/v4112650
View details for Web of Science ID 000311429900011
View details for PubMedID 23202498
View details for PubMedCentralID PMC3509666
View details for Web of Science ID 000278589300002
The seed of the plant Jatropha curcas contains a toxic protein, designated as curcin, which was purified to apparent homogeneity by the combined use of chromatography on Sephdex G-100. The molecular weight of 28.2 kDa and the pI of 8.54 were determined. The protein was found to be a glycoprotein; the total neutral-surge content was 4.91%. It strongly inhibits the protein synthesis of rabbit reticulocyte lysate, with an IC(50) of 0.42 nM. It was determined by Edman that the sequence of the N-terminal thirty-two amino acids was: A-G/Y-S/K-T/A-P/D-T-L-T-I-T-Y-D-A-T/A-A-D-K-K-N-Y-A-Q-F-I-K-D-L-R-E-A-F/A-G. The isolated curcin had a hemagglutinating activity, when its concentration was more than 7.8 mg/L. The secondary structure of curcin was analyzed by Circular Dichroism (CD) spectrum. The result shows the curcin contains alpha-helix (22.3%), beta-sheet (43.5%), and random coil and corner (34.2%). The results of acute toxicity in mice show that mice oral semi-lethal dose LD(50) was 104.737 +/- 29.447 mg/kg; mice parenteral semi-lethal dose LD(50) was 67.20 +/- 10.445 mg/kg.
View details for DOI 10.1080/10826060903558588
View details for Web of Science ID 000275274900002
View details for PubMedID 20213572
View details for Web of Science ID 000270306200009
View details for Web of Science ID 000270306200010