- Renal Transplantation Outcomes and Treatments
- Scoliosis diagnosis and treatment
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Spinal Fractures and Fixation Techniques
- Anesthesia and Pain Management
- Transplantation: Methods and Outcomes
- Erythropoietin and Anemia Treatment
- Respiratory Support and Mechanisms
- Organ Transplantation Techniques and Outcomes
- Acute Kidney Injury Research
- Musculoskeletal Disorders and Rehabilitation
- Monoclonal and Polyclonal Antibodies Research
- Healthcare Policy and Management
- Cardiac, Anesthesia and Surgical Outcomes
- Alcohol Consumption and Health Effects
- S100 Proteins and Annexins
- Intraoperative Neuromonitoring and Anesthetic Effects
- Liver Disease Diagnosis and Treatment
- Hip and Femur Fractures
- Abdominal Surgery and Complications
- Diet and metabolism studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Renal Diseases and Glomerulopathies
- Inflammasome and immune disorders
Chapman University
2022-2025
Seattle Children's Hospital
2024
Orthopedic Center
2019-2023
Keck Graduate Institute
2019-2023
Johns Hopkins University
2019-2022
Johns Hopkins Medicine
2019-2022
Children's Hospital of Los Angeles
2017-2021
University of California, Berkeley
2019-2021
University of California, San Francisco
2016-2020
Development Fund
2020
Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established animal models. We conducted a pilot safety feasibility trial of autologous Treg cell therapy three transplant recipients noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received single infusion...
Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection acute rejection (AR) to affect the long-term survival transplant. We present development validation a noninvasive, spot urine-based diagnostic assay based on measurements six urinary DNA, protein, metabolic biomarkers. The performance this detecting kidney injury in both native kidneys allografts presented cohort 601 distinct urine samples. composite score enables diagnosis AR, with...
Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer's disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the Aβ-independent not reported. Existing do cross blood-brain barrier (BBB), therefore we engineered BBB-penetrating TNFI by fusing extracellular domain type-II human receptor (TNFR) to...
Study Design. Multicenter prospective. Objective. To assess the effect of intraoperative interventions in restoring neuromonitoring (IONM) signals pediatric spine surgery. Summary Background Data. No prior studies have prospectively examined rate return IONM by increasing blood pressure (BP) alone. Methods. Patients undergoing posterior spinal deformity surgery were enrolled at their preoperative appointment. Surgeons completed an data form on patients who experienced change defined as a 50%...
Abstract Polymerase Chain Reaction (PCR) is an essential method in molecular diagnostics and life sciences. PCR requires thermal cycling for heating the DNA strand separation cooling it replication. The process uses a specialized hardware exposes biomolecules to temperatures above 95 °C. Here, we engineer PcrA M6 helicase with enhanced speed processivity replace step by enzymatic unwinding while retaining desired characteristics. We name this isothermal amplification SHARP (SSB-Helicase...
The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors early-stage disease. Measures that can detect chronic disease in its earlier stages needed to enable therapeutic intervention reduce adverse outcomes We have developed the Kidney Injury Test (KIT) a novel KIT Score based on composite measurement validation multiple biomarkers across unique set 397 urine samples. test is performed samples require no processing at site...
Abstract Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6-month formulation approved prostate cancer therapy. This the first study in patients with CPP. efficacy safety of CPP were investigated. primary objective was to evaluate achieving luteinizing hormone (LH) suppression pre-pubertal levels at month 6. international, non-comparative phase III over 48 weeks. Eighteen medical centers US, Chile...
A Common Rejection Module (CRM) consisting of 11 genes expressed in allograft biopsies was previously reported to serve as a biomarker for acute rejection (AR), correlate with the extent graft injury, and predict future damage. We investigated use this gene panel on urine cell pellet kidney transplant patients. Urinary sediments collected from patients biopsy-confirmed rejection, borderline AR (bAR), BK virus nephropathy (BKVN), stable grafts normal protocol (STA) were analyzed expression...
Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity specificity conventionally required bronchoscopies biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of injury transplant recipients CXCL10 reported the tissue patients undergoing CLAD. This study used a novel cfDNA assay evaluate noninvasive assessment CLAD phenotype prediction survival from bronchoalveolar lavage (BAL) fluid. A total 60 BAL...
Rationale Recent studies suggest that similar injury mechanisms are in place across different solid organ transplants, resulting the identification of a common rejection module (CRM), consisting 11 genes overexpressed during acute and, to lesser extent, chronic allograft rejection. Objectives We wanted evaluate usefulness CRM identifying (AR) and phenotypes lung transplant (CLAD), i.e., bronchiolitis obliterans syndrome (BOS) restrictive (RAS), using transbronchial brushings,...
In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for detection of biopsy-confirmed acute rejection in kidney transplants. Using cohort 223 distinct urine samples collected three independent sites both adult pediatric renal transplant patients, examined diagnostic utility allografts. Statistical models based upon measurements six QSant biomarkers (cell-free DNA, methylated-cell-free clusterin,...
Heavy alcohol consumption is a known risk factor for various forms of dementia and the development Alzheimer’s disease (AD). In this work, we investigated how intragastric feeding may alter liver-to-brain axis to induce and/or promote AD pathology. Four weeks mice, which causes significant fatty liver (steatosis) injury, caused no changes in pathology markers brain [amyloid precursor protein (APP), presenilin], except decrease microglial cell number cortex brain. Interestingly, decline...
Abstract Background Biologic TNF-α inhibitors (bTNFIs) can block cerebral in Alzheimer’s disease (AD) if these macromolecules cross the blood–brain barrier (BBB). Thus, a model bTNFI, extracellular domain of type II receptor (TNFR), which bind to and sequester TNF-α, was fused with mouse transferrin antibody (TfRMAb) enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR be protective amyloidosis (APP/PS1) tauopathy (PS19), herein investigated its effects...
Background Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of feeding to AD mice have utilized young and delivered in water without controlling nutritional intake. Objective To study the impact Lieber-DeCarli (LDC) liquid diet, which balances intake, on pathology aged Tg2576 wild-type (WT) mice, unexplored. Methods 13-month-old male female or WT were fed LDC diet (5% ethanol control) six weeks...
Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related non-immune immune injuries can cause slow deterioration premature failure of organ transplants. Diagnosis these by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially pediatric cohorts. We investigated the metabolomic profiles biopsy matched samples from 310 unique kidney transplant recipients using gas chromatography-mass spectrometry...
Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible EDCs during a critical developmental window occurring on embryonic days (E) 15.5–17.5. However, androgen signaling begins E13.5 when receptor (AR) protein in genitalia and testosterone circulating. We hypothesize prior established sensitizes future disruption. To test this hypothesis, CD1 dams were exposed...
Background: Recently, there have been several reports of using an enhanced discharge pathway following posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS). No previous studies prospectively examined patient satisfaction AIS pathway. The purpose this study was to evaluate for PSF and whether felt that their length stay appropriate. Methods: Patients undergoing were enrolled. At first postoperative clinic visit, administered a survey regarding experience....
Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein EPO a chimeric monoclonal antibody targeting mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives into brain via receptor-mediated transcytosis across BBB increases its peripheral clearance to reduce EPO. Our previous work shows protective this BBB-penetrating in AD mice but hematologic have...
Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as drug-delivery vectors has revealed effect dosing regimen, valency, and affinity on uptake, TfR expression, Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous mice. effects high-affinity bivalent TfRMAb murine region, without fusion...
Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the receptor (TNFR), biologic TNFI that sequesters TNF-α, to transferrin antibody (TfRMAb) deliver into brain across blood–brain barrier (BBB). TfRMAb-TNFR was protective 6-month-old transgenic APP/PS1 mice our previous work. However, effects safety following delayed chronic treatment are unknown. Herein, we initiated when male were 10.7...
Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity specificity. The Kidney Injury Test (KIT) Assay urinary biomarkers has previously been shown to distinguish between various pathologies, including chronic disease, nephrolithiasis, transplant rejection. This validation study uses the KIT investigate clinical utility non-invasive detection IgAN predicting progression renal damage over time....