A5101480458- Renal Transplantation Outcomes and Treatments
- Gut microbiota and health
- Cancer Genomics and Diagnostics
- Clostridium difficile and Clostridium perfringens research
- Cytomegalovirus and herpesvirus research
- COVID-19 Clinical Research Studies
- Organ Transplantation Techniques and Outcomes
- Urinary Tract Infections Management
- Single-cell and spatial transcriptomics
- Pharmacological Effects and Toxicity Studies
- Pregnancy and Medication Impact
- Mycobacterium research and diagnosis
- Renal Diseases and Glomerulopathies
- Renal and Vascular Pathologies
- Prenatal Screening and Diagnostics
- Metabolomics and Mass Spectrometry Studies
- Polyomavirus and related diseases
- SARS-CoV-2 and COVID-19 Research
- Pediatric Urology and Nephrology Studies
- Organ Donation and Transplantation
- Muscle and Compartmental Disorders
- Long-Term Effects of COVID-19
- Sinusitis and nasal conditions
- Urinary Bladder and Prostate Research
- Immune Cell Function and Interaction
New York Hospital Queens
2016-2025
NewYork–Presbyterian Hospital
2016-2025
Cornell University
2016-2025
Peninsula Health
2025
Weill Cornell Medicine
2017-2024
University of California, Los Angeles
2023
Dignity Health
2023
Columbia University
2023
The Rogosin Institute
2023
Creative Commons
2023
Abstract The origin of most bacterial infections in the urinary tract is often presumed to be gut. Herein, we investigate relationship between gut microbiota and future development bacteriuria infection (UTI). We perform microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients metagenomic a subset urine supernatant specimens. report that 1% relative abundance Escherichia an independent risk factor for UTI Enterococcus bacteriuria....
Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because much interpatient and intrapatient variability drug absorption, metabolism, disposition. In view the reported impact gut microbial species on we investigated relationship between microbiota tacrolimus requirements this pilot study adult kidney transplant recipients. Serial fecal specimens were collected during first month transplantation from 19 who either required 50% increase...
The gut microbiome plays a role in the regulation of immune system.We prospectively enrolled 26 kidney transplant recipients and collected serial fecal specimens (N=85) during first three months transplantation. We characterized bacterial composition by polymerase chain reaction amplification 16S rRNA V4-V5 variable region deep sequencing using Illumina MiSeq platform.An increase relative abundance Proteobacteria was observed posttransplantation compared to pretransplantation (P=0.04,...
Urinary tract infections are one of the most common in humans. Here we tested utility urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics bacterial viral infections. We isolated cfDNA from 141 urine samples a cohort 82 kidney transplant recipients performed next-generation sequencing. found that is highly informative about composition microbiome, antimicrobial susceptibility, growth dynamics, allograft injury, response infection. These different layers...
Urinary tract infection (UTI) is a frequent, serious complication in kidney allograft recipients.
Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of <i>Faecalibacterium prausnitzii</i> tacrolimus dose in kidney transplant patients, we tested whether <i>F. other gut abundant bacteria are capable metabolizing tacrolimus. Incubation with led to production two compounds (the major one named M1), which was not observed upon incubation hepatic...
Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology a potential basis for diarrhea, we investigated whether posttransplant dysbiosis. We enrolled 71 recipients serial fecal specimen collections first 3 months transplantation profiled microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower 28 diarrheal...
The COVID-19 pandemic has brought unprecedented challenges to the transplant community. reduction in transplantation volume during this time is partly due concerns over potentially increased susceptibility and worsened outcomes of immunosuppressed recipients. consequences on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 80 recipients diagnosed with between March 13 May 20, 2020. Despite similar demographics burden comorbidities...
Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course outcome of Covid-19 in this population identify safe therapeutic strategies.We performed a retrospective chart review 73 adult kidney evaluated from 13 March 20 April 2020. Primary outcomes included recovery symptoms, acute injury, failure case fatality rate.Of patients screened, 54...
High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional sequencing, however, does not integrate information about the host, which is often critical distinguish infection from infectious disease, and assess severity of disease. Here, we explore utility high-throughput cell-free DNA (cfDNA) after bisulfite conversion map tissue cell types origin host-derived cfDNA, profile bacterial viral metagenome. We applied this assay 51...
Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize full benefits transplantation. To investigate whether urine metabolites predict status, we determined levels 749 1516 samples from 241 graft recipients enrolled prospective multicenter Clinical Trials Organ Transplantation-04 study. A metabolite signature ratio 3-sialyllactose to xanthosine biopsy specimen-matched supernatants best discriminated specimens without rejection. For...
Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity mortality. Recent evidence supports role for the gut as source UTIs but little known about relationship between commensal bacteria UTI development. We hypothesized that abundance of associated with lower risk developing bacteriuria UTIs. performed microbiome profiling using 16S rRNA gene sequencing V4-V5 hypervariable region on 510 fecal specimens 168 recipients....
Vitamin D, in addition to its established role bone metabolism, may regulate the immune system and affect outcome of allografts.We identified 351 kidney allograft recipients who had serum levels 25-hydroxyvitamin D (25[OH]D) measured within first 30 days transplantation. We evaluated relationship between circulating 25(OH)D acute cellular rejection (ACR), cytomegalovirus (CMV) disease, BK virus nephropathy, graft function.Vitamin deficiency (circulating 25[OH]D ≤20 ng/mL, defined using The...
Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition HLA, may serve as stimuli well targets for anti-allograft immune response and influence long-term outcomes. We therefore performed exome sequencing of DNA from recipients their living donors estimated all possible cell antigens mismatches a given donor/recipient pair by computing number amino acid trans-membrane...
Abstract Background The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate‐producing (BPG) bacteria and less frequent lower respiratory viral in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship abundance BPG a cohort kidney recipients. Methods We recruited 168 who provided...
Abstract Background Cell-free DNA (cfDNA) in blood, urine, and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria viruses, creating opportunities for the diagnosis infection via metagenomic sequencing. The total biomass microbial-derived clinical isolates low, which makes sequencing susceptible to contamination alignment noise. Results Here, we report low background correction (LBBC), bioinformatics noise filtering tool informed by...
Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and treat autoimmune diseases. MMF usage, however, limited by severe gastrointestinal toxicity that observed in approximately 45% of recipients. The active form the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation bacterial β-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within tract. GUS enzymes...
Background Identifying bacterial taxa associated with disease phenotypes or clinical treatments over time is critical for understanding the underlying biological mechanism. Association testing microbiome data already challenging due to its complex distribution that involves sparsity, over-dispersion, heavy tails, etc. The longitudinal nature of adds another layer complexity - one needs account within-subject correlations avoid biased results. Existing differential abundance approaches...
Noninvasive tests to differentiate the basis for acute dysfunction of kidney allograft are preferable invasive biopsies. We measured absolute levels 26 prespecified mRNAs in urine samples collected from graft recipients at time for-cause biopsy and investigated whether differential diagnosis is feasible using urinary cell mRNA profiles. profiled 52 patients with specimens indicating rejection (26 T cell–mediated antibody-mediated rejection) 32 tubular injury without rejection. A stepwise...
Acute rejection of human allografts has been viewed mostly through the lens adaptive immunity, and intragraft landscape innate immunity genes not characterized in an unbiased fashion. We performed RNA sequencing 34 kidney allograft biopsy specimens from adult recipients; 16 were categorized as Banff acute T cell–mediated (TCMR) 18 normal. Computational analysis mRNA transcriptome identified significantly higher abundance for pattern recognition receptors TCMR compared with normal biopsies,...
BACKGROUND. RNA sequencing (RNA-Seq) is a molecular tool to analyze global transcriptional changes, deduce pathogenic mechanisms, and discover biomarkers. We performed RNA-Seq investigate gene expression biological pathways in urinary cells kidney allograft biopsies during an acute rejection episode determine whether cell patterns are enriched for biopsy profiles.
We tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states yield insights to decipher complex heterogeneity alloimmune injury. selected 3 cortex from individuals for scRNA-seq processed them fresh using an identical protocol on 10x Chromium platform; (i) HK: native biopsy a living donor, (ii) AK1: with transplant glomerulopathy, tubulointerstitial fibrosis, worsening graft function, (iii) AK2:...