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Xinxia Peng

Assoc Professor

he/him/his

CVM Research Building 492

Bio

SHORT DESCRIPTION OF INTERESTS:
I am interested in using genomics and bioinformatics approaches to investigate the impact of climate change on host-microbiome-pathogen interactions and microbial pathogenesis especially emerging pathogens.

(Expertise: Genomics, bioinformatics, infectious disease, immunology, microbiome analysis)

https://penglab.cvm.ncsu.edu/

Publications

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Grants

Date: 04/01/23 - 1/31/28
Amount: $1,206,978.00
Funding Agencies: National Institutes of Health (NIH)

Childbirth at advanced maternal age (i.e., ???35 years old) is associated with increased risk of adverse pregnancy outcomes such as preterm birth, preeclampsia and intrauterine growth restriction. A significant portion of reproductive aging research has focused on ovarian function and gamete quality, but we recently identified a prominent age-associated alteration in uterine environment, independent of hormone levels, as a prevalent cause of reproductive decline in older females. Because the uterine environment defines the systematic maternal effects on embryo development, understanding the precise mechanisms by which uterus ages is a prerequisite for ultimately developing counteracting measures. The goal of this proposal is to investigate the molecular mechanisms that underlie the age-associated uterine response to pregnancy.

Date: 07/01/18 - 6/30/25
Amount: $468,933.00
Funding Agencies: National Institutes of Health (NIH)

Dr. Peng and members of his laboratory will conduct parallel bioinformatic studies and computational modeling of transcriptomic and microbiome data sets generated by the Nonhuman Primate Core Functional Genomics Laboratory for AIDS Vaccine Research and Development. He will apply his computational strategy for quantifying the allele-specific expression of macaque complex immune genes like MHC genes to specific data sets received from the Core. This strategy may involve the utilization of PacBio Iso-Seq data to accurately define the full-length transcripts and alternative splicing patterns for macaque MHC alleles. Additionally, when requested, he will apply advanced methods for correlating microbiome composition and infection- or vaccine-induced host transcriptional responses. Dr. Peng will oversee all activities at North Carolina State University. He will participate in monthly web conferences with other members of the Core and DAIDS representatives, submit monthly progress reports to the University of Washington, and attend annual programmatic site visits held in Seattle WA.

Date: 05/04/19 - 4/30/25
Amount: $2,653,489.00
Funding Agencies: National Institutes of Health (NIH)

Voice impairment is the most common communication disorder with nearly 20 million people in the US reporting symptoms of dysphonia annually. The cost of treatment and lost wages for this disorder is approaching $13 billion. The etiology of these disorders is diverse, but given their anatomic location, the vocal folds (VFs) are susceptible to a multitude of injurious stimuli, including reflux of gastric contents, iatrogenic injury, and the inherent trauma associated with voice production. Injury can result in altered lamina propria (LP) architecture resulting in aberrant phonatory physiology. To date, no treatment restores the native VF extracellular matrix (ECM) composition, structure, and function following VF injury which likely underlies suboptimal outcomes for patients with VF scar. ECM scaffolds, if appropriately processed, can be used as resorbable and naturally derived biomaterials with a safe record of clinical use that promote tissue remodeling while reducing fibrosis. Tissue-specific ECM hydrogels are ideal for clinical application, particularly given the emerging practice and distinct advantages of in-office procedures using minimally invasive approaches. Work from our group and others provide promising data regarding the role of decellularized vocal fold lamina propria (VFLP-ECM) as a therapeutic scaffold. We broadly hypothesize that VFLP-ECM will evolve into clinical practice to provide a scaffold that promotes functional repair of the VFs. Specifically, we seek to develop an injectable vocal fold lamina propria hydrogel (VFLP-ECMh) that will degrade over time while harnessing the stimulatory effects of the ECM to drive vocal fold tissue remodeling

Date: 02/06/23 - 1/31/25
Amount: $212,800.00
Funding Agencies: National Institutes of Health (NIH)

This application is a two-way consortium between the laboratories of the PI Dr. Jean Kwun at Duke University (Duke) and Dr. Xinxia Peng at the North Carolina State University (NC State). In this application, Duke Team will oversee the collection, cryopreservation, and transfer of rhesus samples of single cell suspensions. Dr. Peng and members of his laboratory will conduct high-throughput single cell based Ig and TCR repertoire and transcriptome sequencing analysis of cryopreserved rhesus samples provided by the Duke team.

Date: 12/01/18 - 11/30/24
Amount: $2,680,311.00
Funding Agencies: National Institutes of Health (NIH)

Voice impairment is the most common communication disorder with nearly 20 million people in the US reporting symptoms of dysphonia annually. The cost of treatment and lost wages for this disorder is approaching $13 billion. The etiology of these disorders is diverse, but given their anatomic location, the vocal folds (VFs) are susceptible to a multitude of injurious stimuli, including reflux of gastric contents, iatrogenic injury, and the inherent trauma associated with voice production. Injury can result in altered lamina propria (LP) architecture resulting in aberrant phonatory physiology. To date, no treatment restores the native VF extracellular matrix (ECM) composition, structure, and function following VF injury which likely underlies suboptimal outcomes for patients with VF scar. ECMs, if appropriately processed, can be used as resorbable and naturally derived biomaterials with a safe record of clinical use that promote tissue remodeling while reducing fibrosis. Injectable hydrogels are ideal for clinical application and cell delivery, particularly given the emerging practice and distinct advantages of in-office procedures using minimally invasive approaches. Work from our group and others provide promising data regarding the role of decellularized vocal fold lamina propria (VFLP-ECM) as an injectable agent or as a delivery vehicle for therapeutic cells such as mesenchymal stem cells. We broadly hypothesize that VFLP-ECM hydrogels (with or without stem cells) will evolve into clinical practice to provide a scaffold that promotes functional repair of the VFs. Specifically, we seek to develop an injectable vocal fold lamina propria hydrogel (VFLP-ECM-H) that will degrade over time while harnessing the stimulatory effects of the ECM to drive vocal fold tissue remodeling.

Date: 05/01/23 - 4/30/24
Amount: $334,400.00
Funding Agencies: National Institutes of Health (NIH)

The Computational Immunobiology Core (CIC) will provide comprehensive technical assay support services and analytic support for the hypothesis-driven research studies proposed in the two Projects comprising this U19 proposal. Led by Dr. Kirk, the Core continues to utilize the longstanding assets of prior iterations of this program to achieve comprehensive characterization of transplant procedures, with particular expertise in polychromic flow cytometry-based platforms for immune profiling. To this established team, a new collaboration has been forged with NC State University, an international leader in veterinary medicine, to incorporate a novel platform for comprehensive, rhesus macaque-specific, single cell RNA sequence analysis. This is the first lab to comprehensively provide RNA sequence analysis for the entire TCR and BCR repertoire in the rhesus macaque, and as such, adds unprecedented granularity to the analysis of the in vivo studies proposed in the two Projects. Given the exponential growth in data acquired from these capabilities, new expertise in high-density data analytics has been added through the recruitment of Drs. Peng and Chan. These individuals have extensive expertise in the integration of sequence- and flow-based datasets with traditional metrics of clinical outcome, specifically in nonhuman primate studies.

Date: 05/01/20 - 4/30/24
Amount: $246,307.00
Funding Agencies: National Institutes of Health (NIH)

Dr. Peng and members of his laboratory will conduct 16S rRNA based microbiome analysis of vaginal samples provided by the UNC team. Dr. Peng and his group will use the generated 16S data to identify microbes related to the ascending infection of Chlamydia. His group will process the raw 16S data including quality control and provide the management and dissemination of the generated 16S sequencing data.

Date: 05/01/19 - 4/30/24
Amount: $116,767.00
Funding Agencies: National Institutes of Health (NIH)

Dr. Peng and members of his laboratory will conduct 16S rRNA based microbiome analysis of vaginal samples provided by the UNC team. Dr. Peng and his group will use the generated 16S data to identify microbes related to the ascending infection of Chlamydia. His group will process the raw 16S data including quality control and provide the management and dissemination of the generated 16S sequencing data.

Date: 09/30/21 - 9/29/23
Amount: $402,340.00
Funding Agencies: National Institutes of Health (NIH)

Ferrets and Syrian (golden) hamsters are two leading small animal models for respiratory infections. However, a well-known challenge for both models is the overall lack of species-specific reagents and tools. In particular, immunoglobulin (Ig) and T-cell receptor (TCR) repertoire analysis is key to understand the development of antigen-specific immunity during infection and vaccination. Currently, very little is known about ferret and hamster Ig/TCR repertoires, significantly limiting the options to monitor their immune response to experimental infections and vaccinations. Dedicated efforts using special strategies are necessary to analyze complex immune loci like Ig/TCR regions. Recently we reported a novel and efficient strategy to construct complete Ig and TCR reference sequences for rhesus macaque, which has been plagued by a lack of similar immune resources. We also successfully designed rhesus-specific single cell level Ig and TCR repertoire assays, which are completely comparable to those available for human and mouse. Here, we propose using the same approach to develop public resources and assays to enable Ig and TCR repertoire analysis in both ferrets and hamsters. This project includes two Specific Aims. In Aim 1, we will obtain a large number of high-quality, full-length Ig and TCR transcript sequences using an established long read transcriptome sequencing protocol for both hamsters and ferrets. We will apply custom bioinformatics methods to identify full-length species-specific Ig/TCR transcript sequences and variable region genes and to curate constant region reference sequences for both species. In Aim 2, we will use the reference sequences obtained in Aim 1 to design species-specific single cell B- and T-cell V(D)J assays, similar to our design for rhesus macaque. We will experimentally validate these species-specific V(D)J assays using hamster and ferret samples. These resources and assays will provide the ability to perform single-cell sequencing and Ig and TCR repertoire analysis in both species vaccinated against and/or infected with pathogens.

Date: 04/01/20 - 6/30/23
Amount: $2,199,138.00
Funding Agencies: National Institutes of Health (NIH)

Currently, ischemic damage to the heart cannot be repaired by conventional medical care therefore only palliative treatments exist. Stem cell transplantation is a promising strategy for therapeutic cardiac regeneration, but current therapies are limited by insufficient interaction between the regenerative cells and the injured tissue. In the last grant period, we have developed targeted nanoparticles (namely bispecific antibody-conjugated agents) to redirect circulating stem cells to the infarcted heart for therapeutic regeneration. Despite such initial success, we realize our system has some problems: (P1) We cannot fully reply on the stem cells (????????????????seeds???????????????) for cardiac repair. The post-injury heart microenvironment (????????????????soil???????????????) needs to be primed for the maximum outcome; (P2) Antibody targeting is quite specific but is fully dependent on the antigen, which are cardiac injury biomarkers that only expresses in a short period of time after injury. The current renewal proposal builds on the previous study, but represents a significant advancement, both technically and conceptually. To address P1, we reason one of the antibodies needs to be therapeutic, to combat the excessive inflammation in the heart. To address P2, we seek for agents that have broad spectrum affinity with cardiac injury. To those ends, we developed anti-IL-1 platelet mimetic (IL1-PM). The mode of action for IL1-PM is as follows: platelet vesicles serve as the carrier of our system and they have innate ability to find cardiac injury (replying on the binding motifs on platelet membranes); anti-IL-1 antibodies are currently in Phase 3 clinical trials and have demonstrated ability to neutralize inflammation and promote cardiac repair; platelet vesicles can be further loaded with stem cell-derived growth factors to aid the repair process. AIM 1: Fabricate IL1-PM and characterize its physicochemical and biological properties. We will generate IL1-PM agents by conjugating anti IL-1 antibodies onto platelet membrane nanovesicles; binding/engaging ability, toxicity, pharmacokinetics of IL1-PM will be examined in cultured cells and in healthy animals. AIM 2: Determine the therapeutic potential of mesenchymal stem cell (MSC) secretome-loaded IL1-PM in a mouse model of myocardial infarction. MI will be induced by ischemia-reperfusion. After that, MSC-IL1-PM, along with various control agents, will be delivered intravenously. Therapeutic safety and efficacy will be determined. In addition,the underlying mechanisms of such treatment will be explored. AIM 3: Translate the findings into a clinically-relevant large animal model of myocardial infarction. MI will be induced in swine via a balloon-occlusion procedure. The safety and efficacy of MSC-IL1-PM treatment will be evaluated. Our therapeutic system combines stem cell therapy (component 1) and anti-IL1 therapy (component 2), both of which have been rigorously tested and verified in clinical trials for cardiac repair. Moreover, the therapeutics will be delivered in a targetable fashion relying on the injury-finding ability of platelet binding motifs (component 3). All 3 components have been supported by strong preliminary data from our group.


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