About

Xiaoyu Yang is a graduate student in the Department of Linguistics at the University of Maryland. Her research expertise includes neurolinguistics, semantics, and syntax. She is affiliated with the Department of Linguistics located at 1401 Marie Mount Hall, College Park, MD 20742, and can be contacted via email at xyang99@umd.edu. Her work focuses on understanding the neural mechanisms underlying language processing and the semantic and syntactic aspects of linguistics.

Research topics

• Biology
• Microbiology
• Virology
• Genetics
• Cell biology

Selected publications

• Safety assessment of proteasome inhibitors real world adverse event analysis from the FAERS database

  Scientific Reports · 2025-04-04 · 4 citations

  articleOpen access

  Proteasome inhibitor analogs (PIs) have significantly improved the degree of remission and survival rate of patients with multiple myeloma. However, serious adverse events (AEs) have hindered their clinical application. This study analyzed the AEs reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine the safety profile and differences for the PI drugs bortezomib, carfilzomib, and ixazomib. The reporting odds ratio (ROR) was used to detect safety signals. Significant safety signals were detected based on system-organ classification (SOC). For bortezomib, the most significant SOC signal was "blood and lymphatic system disorders" (ROR = 3.47, 95% CI 3.37-3.57), while the most significant PT signal was "enteric neuropathy" (ROR = 134.96, 95% CI 45.67-398.79). For carfilzomib, the most significant SOC signal being "blood and lymphatic system disorders" (ROR = 4.34, 95% CI 4.17-4.53), while the most significant PT signal was "light chain analysis increased" (ROR = 76.65, 95% CI 57.07-102.96). For ixazomib, the most significant SOC signal was "gastrointestinal disorders" (ROR = 2.04, 95% CI 1.96-2.12), while the most significant PT signal was "light chain analysis increased" (ROR = 67.15, 95% CI 45.36-99.42). For bortezomib and carfilzomib, the top 20 reported PTs were consistent with AEs listed in the drug information. For ixazomib, six unexpected AEs were observed: asthenia, malaise, pyrexia, decreased appetite, dehydration, and falls. The PIs were consistent with the early failure model based on time-series analysis of the occurrence of adverse reactions to the drug. The data mined from FAERS generates new AE signals, and further clinical studies are needed to validate these findings.

  PublisherOA PDFDOI

• Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine

  Nature Communications · 2025-04-06 · 5 citations

  articleOpen access

  Abstract Borrelia burgdorferi ( Bb ) causes Lyme disease (LD), one of the most common vector-borne diseases in the Northern Hemisphere. Here, we solve the crystal structure of a mutated Bb vaccine antigen, CspZ-YA that lacks the ability to bind to host complement factor H (FH). We generate point mutants of CspZ-YA and identify CspZ-YA I183Y and CspZ-YA C187S to trigger more robust bactericidal responses. Compared to CspZ-YA, these CspZ-YA mutants require a lower immunization frequency to protect mice from LD-associated inflammation and bacterial colonization. Antigenicity of wild-type and mutant CspZ-YA proteins are similar, as measured using sera from infected people or immunized female mice. Structural comparison of CspZ-YA with CspZ-YA I183Y and CspZ-YA C187S shows enhanced interactions of two helices adjacent to the FH-binding sites in the mutants, consistent with their elevated thermostability. In line with these findings, protective CspZ-YA monoclonal antibodies show increased binding to CspZ-YA at a physiological temperature (37 °C). In summary, this proof-of-concept study applies structural vaccinology to enhance intramolecular interactions for the long-term stability of a Bb antigen while maintaining its protective epitopes, thus promoting LD vaccine development.

  PublisherOA PDFDOI

• Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo

  Immunity · 2025-06-16 · 15 citations

  article1st authorCorresponding
  PublisherDOI

• Long-Term Outcomes of Dose Escalation in Definitive Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Randomized Phase III Trial

  International Journal of Radiation Oncology*Biology*Physics · 2025-09-01

  articleOpen access
  PublisherOA PDFDOI

• Complement therapeutic factor H-IgG proteins as pre-exposure prophylaxes against Lyme borreliae infections

  The Journal of Immunology · 2025-08-22 · 1 citations

  articleOpen access

  Lyme disease (LD) is the most common vector-borne disease in the northern hemisphere and is caused by the bacteria Borrelia burgdorferi sensu lato (also known as Lyme borreliae) with no effective prevention available. Lyme borreliae evade complement killing, a critical arm of host immune defense, by producing outer surface proteins that bind to a host complement inhibitor, factor H (FH). These outer surface proteins include CspA and CspZ, which bind to the sixth and seventh short consensus repeats (SCR6-7) of FH and the OspE family of proteins (OspE), which bind to the nineteenth and twentieth SCR (SCR19-20). In this study, we produced 2 chimeric proteins, FH-Fc, containing the Fc region of immunoglobulin G (Fc) with SCR6-7 or SCR19-20. We found that both FH-Fc constructs killed B. burgdorferi via bacterial lysis and phagocytosis and reduced bacterial colonization and LD-associated joint inflammation in vivo. While SCR6-7-Fc displayed Lyme borreliae species-specific bacterial killing, SCR19-20-Fc versatilely eradicated all tested bacterial species/strains. This correlated with SCR6-7-Fc binding to select variants of CspA and CspZ, but SCR19-20-Fc binding to all tested OspE variants. Overall, we demonstrated the concept of using FH-Fc constructs to kill Lyme borreliae and defined underlying mechanisms, highlighting the potential of FH-Fc as a pre-exposure prophylaxis against LD infection.

  PublisherOA PDFDOI

• Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen

  mBio · 2025-01-28 · 5 citations

  articleOpen accessSenior author

  ABSTRACT In Borrelia burgdorferi , the causative agent of Lyme disease, differential gene expression is primarily governed by the alternative sigma factor RpoS (σ S ). Understanding the regulation of RpoS is crucial for elucidating how B. burgdorferi is maintained throughout its enzootic cycle. Our recent studies have shown that the homolog of Fur/PerR repressor/activator BosR functions as an RNA-binding protein that controls the rpoS mRNA stability. However, the mechanisms regulating BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we uncovered a positive feedback loop between RpoS and BosR, wherein RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of rpoS significantly reduced BosR levels, whereas artificial induction of rpoS resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect bosR mRNA levels but instead modulates the turnover rate of the BosR protein. Moreover, we demonstrated that environmental cues do not directly influence bosR expression but instead induce rpoS transcription and RpoS production, thereby enhancing BosR protein levels. These findings reveal a new layer of complexity in the RpoN-RpoS regulatory pathway, challenging the existing paradigm and suggesting a need to re-evaluate the factors and signals previously implicated in regulating RpoS via BosR. This study provides new insights into the intricate regulatory networks underpinning B. burgdorferi ’s adaptation and survival in its enzootic cycle. IMPORTANCE Lyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent, Borreliella (or Borrelia ) burgdorferi , is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection of B. burgdorferi . This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disrupt B. burgdorferi ’s enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria.

  PublisherDOI

• Cost-effectiveness analysis of eribulin versus dacarbazine in patients with advanced liposarcoma

  Scientific Reports · 2025-01-15 · 3 citations

  articleOpen accessSenior author

  A subgroup analysis of a randomized study demonstrated that patients with advanced or metastatic liposarcoma treated with eribulin had longer overall survival and progression-free survival compared to those treated with dacarbazine, suggesting eribulin as a therapeutic option for advanced liposarcoma. Therefore, this study aims to evaluate the cost-effectiveness of eribulin versus dacarbazine in the treatment of advanced liposarcoma. We established a 10-year Markov model to compare the cost-effectiveness of eribulin and dacarbazine regimens. Clinical data were sourced from a subgroup analysis of a multicenter, randomized, open-label phase 3 trials. Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed. The total cost of the dacarbazine scheme was $10,895.558, with a QALY of 0.533. In contrast, the total cost of the eribulin scheme was $16,961.891, with a QALY of 0.698. The ICER between the eribulin and dacarbazine schemes was $36,736.467, which is below the willingness-to-pay (WTP) threshold in China ($37,877.469). From the perspective of the Chinese healthcare system, eribulin is cost-effective compared to dacarbazine at the WTP threshold.

  PublisherDOI

• Borrelial phosphomannose isomerase as a cell surface localized protein that retains enzymatic activity and promotes host-pathogen interaction

  mBio · 2025-02-11 · 3 citations

  articleOpen access

  ABSTRACT All organisms produce an intracellular Zn 2+ -dependent enzyme, phosphomannose isomerase (PMI) or mannose-6 phosphate isomerase, that catalyzes the reversible conversion of mannose-6-phosphate and fructose-6-phosphate during sugar metabolism and polysaccharide biosynthesis. Unexpectedly, we discovered an additional PMI function in Borrelia burgdorferi , the pathogen of Lyme disease, where the enzyme is localized on the cell surface and binds to collagen IV—a host extracellular matrix component predominantly found in the skin. The AlphaFold 3-based structural model of B. burgdorferi PMI (BbPMI) retains the active site with tetrahedrally-coordinated Zn 2+ seen in other PMIs of known structure, residing in an elongated crevice. Ligand docking shows that the crevice can accommodate the tip trisaccharide moiety of a glycosylated asparagine residue on the collagen IV 7S domain. Low doses of a well-known PMI benzoisothiazolone inhibitor impair the growth of diverse strains of B. burgdorferi in culture, but not other tested Gram-negative or Gram-positive pathogens. Borrelia cells are even more susceptible to several other structurally related benzoisothiazolone analogs. The passive transfer of anti-BbPMI antibodies in ticks can impact spirochete transmission to mice, while the treatment of collagen IV-containing murine skin with PMI inhibitors impairs spirochete infectivity. Taken together, these results highlight a newly discovered role for BbPMI in mediating host-pathogen interactions during the spirochete infectivity process. In turn, this discovery offers an opportunity for the development of a novel therapeutic strategy to combat Lyme disease by preventing the BbPMI interaction with its host receptor, collagen IV. IMPORTANCE All organisms produce an intracellular enzyme, phosphomannose isomerase (PMI), that converts specific sugars during metabolism. Unexpectedly, we discovered an additional PMI function in Borrelia burgdorferi , the Lyme disease pathogen, where the enzyme is localized on the cell surface and binds to collagen IV—a host extracellular molecule mainly found in the skin. Low doses of PMI chemical inhibitors impair the growth of diverse strains of B. burgdorferi in culture, but not other tested bacterial pathogens. The passive transfer of anti-BbPMI antibodies in ticks can impact B. burgdorferi transmission to mice, while the treatment of collagen IV-containing murine skin with PMI inhibitors impairs infectivity. Taken together, these results highlight a newly discovered role for BbPMI in mediating host-pathogen interactions during infection. In turn, this discovery offers an opportunity for the development of a novel therapeutic strategy to combat Lyme disease by preventing BbPMI function and interaction with host collagen IV.

  PublisherDOI

• <i>Borrelia burgdorferi</i> c-di-AMP is a key extracellular pathogen-associated molecular pattern to elicit type I interferon responses in mammalian hosts

  The Journal of Immunology · 2025-07-03 · 2 citations

  articleOpen accessSenior author

  Borrelia burgdorferi (or Borreliella burgdorferi), the extracellular spirochete responsible for Lyme disease, elicits a type I interferon (IFN-I) response critical for the development of Lyme arthritis. However, the specific pathogen-associated molecular pattern (PAMP) driving this response remains unidentified. Previous studies have reported that B. burgdorferi culture supernatants significantly stimulate macrophage IFN-I responses, but the responsible component was unknown. In this study, we identified cyclic-di-adenosine monophosphate (c-di-AMP) as the critical PAMP for the induction of IFN response. Inactivation of cdaA, which encodes diadenylate cyclase for c-di-AMP synthesis, significantly reduced IFN-β production in murine macrophage cell lines (RAW264.7) and bone marrow-derived macrophages. Conversely, the deletion of dhhP, which encodes c-di-AMP phosphodiesterase, dramatically increased IFN-β production. We further demonstrated that B. burgdorferi releases c-di-AMP, which is the major component in the culture supernatant responsible for stimulating the IFN-I response in macrophages. Furthermore, B. burgdorferi c-di-AMP-induced IFN-I response depends on STING, as inactivation or inhibition of STING signaling markedly reduced IFN-I induction. These findings establish c-di-AMP as a key PAMP of B. burgdorferi that activates host STING signaling to induce IFN-I responses, highlighting its potential as a therapeutic target for Lyme arthritis.

  PublisherOA PDFDOI

• MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of <i>Borrelia burgdorferi</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-06-10 · 2 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Borrelia (or Borreliella ) burgdorferi , the causative agent of Lyme disease, is a motile and invasive zoonotic pathogen, adept at navigating between its arthropod vector and mammalian host. While motility and chemotaxis are well established as essential for its enzootic cycle, the function of methyl-accepting chemotaxis proteins (MCPs) in the infectious cycle of B. burgdorferi remains unclear. In this study, we demonstrate that MCP5, one of the most abundant MCPs in B. burgdorferi , is differentially expressed in response to environmental signals as well as at different stages of the pathogen’s enzootic cycle. Specifically, the expression of mcp5 is regulated by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, which are critical for the spirochete’s colonization of the tick vector and mammalian host, respectively. Infection experiments with an mcp5 mutant revealed that spirochetes lacking MCP5 could not establish infections in either C3H/HeN mice or Severe Combined Immunodeficiency (SCID) mice, which are defective in adaptive immunity, indicating the essential role of MCP5 in mammalian infection. However, the mcp5 mutant could establish infection and disseminate in NOD SCID Gamma (NSG) mice, which are deficient in both adaptive and most innate immune responses, suggesting a crucial role of MCP5 in evading host innate immunity. In the tick vector, the mcp5 mutants survived feeding but failed to transmit to mice, highlighting the importance of MCP5 in transmission. Our findings reveal that MCP5, regulated by the Rrp1 and Rrp2 pathways, is critical for the establishment of infection in mammalian hosts by evading host innate immunity and is important for the transmission of spirochetes from ticks to mammalian hosts, underscoring its potential as a target for intervention strategies. SUMMARY Lyme disease is the most commonly reported arthropod-borne illness in the US, Europe, and Asia. The causative agent of Lyme disease, Borrelia burgdorferi , is maintained in an enzootic cycle involving arthropod vectors ( Ixodes ticks) and rodent mammalian hosts. Understanding how B. burgdorferi moves within this natural cycle is crucial for developing new strategies to combat Lyme disease. The complex nature of the enzootic cycle necessitates sensory-guided movement in response to environmental stimuli. B. burgdorferi possesses a unique and intricate chemotaxis signaling system, with methyl-accepting chemotaxis proteins (MCPs) at its core. These proteins are responsible for sensing environmental signals and guiding bacterial movement toward or away from stimuli. This study found that one of the MCPs, MCP5, is highly expressed and differentially regulated during the enzootic cycle by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways. MCP5 is crucial for mammalian infection, aiding in immune evasion and transmission from ticks to mammals, providing a foundation for further research into B. burgdorferi ’s navigation within its hosts.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R03AI092143

  NIH · $152k · 2015

• NIH Grant R21AI085242

  NIH · $397k · 2013

• Regulatory Network of the Lyme Disease Pathogen

  NIH · $5.4M · 2009–2028

• NIH Grant R21AI072144

  NIH · $400k · 2009

• A Novel Tick Protein Influences Persistence of Lyme Disease Pathogens

  NIH · $152k · 2016–2018

Frequent coauthors

• Utpal Pal

  University of Maryland, College Park

  154 shared

• Youyun Yang

  Indiana University – Purdue University Indianapolis

  87 shared

• Meiping Ye

  Nanjing Drum Tower Hospital

  62 shared

• Yongliang Lou

  Wenzhou Medical University

  57 shared

• Xuwu Xiang

  New York University

  57 shared

• Alexis A. Smith

  Walter Reed Army Institute of Research

  54 shared

• Bryan Troxell

  Research Triangle Park Foundation

  52 shared

• Ming He

  52 shared