- Renal Transplantation Outcomes and Treatments
- T-cell and B-cell Immunology
- MicroRNA in disease regulation
- Coronary Interventions and Diagnostics
- Immune Cell Function and Interaction
- Cardiac Arrest and Resuscitation
- Organ Transplantation Techniques and Outcomes
- RNA Interference and Gene Delivery
- Organ Donation and Transplantation
- Cancer-related molecular mechanisms research
- Health Systems, Economic Evaluations, Quality of Life
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Acute Myocardial Infarction Research
- Emergency and Acute Care Studies
- Advanced biosensing and bioanalysis techniques
- Neurological Complications and Syndromes
- Renal Diseases and Glomerulopathies
- Genetic and Kidney Cyst Diseases
- Trauma and Emergency Care Studies
- Molecular Biology Techniques and Applications
- Antiplatelet Therapy and Cardiovascular Diseases
- Sepsis Diagnosis and Treatment
- Renal and related cancers
- Traumatic Brain Injury Research
University of the Pacific
2024
Baptist Hospital
2017-2023
Saint Thomas Midtown Hospital
2017-2023
Arkansas Baptist College
2019-2023
University of Maryland, College Park
2022
University of Colorado Anschutz Medical Campus
2017-2021
University of Colorado Denver
2016-2021
Columbia University
2021
Harvard University
1991-2020
Icahn School of Medicine at Mount Sinai
1972-2019
To extend our understanding of the genetic basis human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study purified CD4(+) T cells monocytes, representing adaptive innate immunity, in a multi-ethnic cohort 461 healthy individuals. Context-specific cis- trans-eQTLs were identified, cross-population mapping allowed, some cases, putative functional assignment candidate causal regulatory variants for disease-associated loci. We note...
MicroRNAs (miRNAs) are a class of 20–24 nt noncoding RNAs that regulate target mRNAs post-transcriptionally by binding with imperfect complementarity in the 3′-untranslated region (3′-UTR) and inhibiting translation or RNA stability. Current understanding miRNA biology is limited, antisense oligonucleotide (ASO) inhibition powerful technique for functionalization vitro vivo, therapeutic targeting miRNAs. Identification optimal ASO chemistries miRNAs therefore great interest. We evaluated...
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of renal failure. Here we identify miR-17 as a target for treatment ADPKD. We report that induced in cysts mouse and human Genetic deletion miR-17∼92 cluster inhibits cyst proliferation PKD progression four orthologous, including two long-lived, models Anti-miR-17 attenuates growth short-term long-term models. inhibition also suppresses primary ADPKD cultures derived from multiple donors....
The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment tensin, an actin-binding component focal contacts and other submembraneous cytoskeletal structures, is reported. derived amino acid sequence revealed presence Src homology 2 (SH2) domain. This domain shared by number signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, family members, transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase,...
Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported show efficacy. Whether this the most relevant endpoint for measuring has not been adequately addressed in field although it important implications evaluating targeting studies. Using novel approach quantitate levels presence excess ASO, we have discovered that outcome can vary depending on chemical modification...
Abstract Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in either PKD1 or PKD2 genes, is one of the most common human monogenetic disorders and leading genetic cause end-stage renal disease. Unfortunately, treatment options for ADPKD are limited. Here we report discovery characterization RGLS4326, a first-in-class, short oligonucleotide inhibitor microRNA-17 (miR-17), as potential ADPKD. RGLS4326 discovered screening chemically diverse rationally designed library...
To determine out-of-hospital cardiac arrest survival rates before and after implementation of the Take Heart America program (a community-based initiative that sequentially deployed all most highly recommended 2005 American Association resuscitation guidelines in an effort to increase survival).Out-of-hospital patients Anoka County, MN, greater St. Cloud, from November June 2009.Two sites Minnesota with a combined population 439,692 people (greater Cloud County) implemented: 1) widespread...
De novo donor-specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common among immunosuppressive approaches used in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not established. We evaluated mean TAC C
Abstract T and B lymphocytes are developmentally functionally related cells of the immune system, representing two major branches adaptive immunity. Although originating from a common precursor, they play very different roles: contribute to drive cell-mediated immunity, whereas secrete Abs. Because their functional importance well-characterized differentiation pathways, ideal cell types with which understand how differences encoded at transcriptional level. there has been great deal interest...
Abstract Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown be upregulated in HCC, but the contribution of this oncomiR maintenance tumorigenic phenotype liver poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors miR-21 (anti-miRNAs) used them interrogate dependency on panel cell lines. Treatment anti–miR-21, not mismatch...
Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney–pancreas recipients FCXM from September 2007 August 2012 therapy were analyzed median follow-up 4.2 years. All...
Background. Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to renal allograft, yet there remains no consensus on how best monitor drug therapy. Both high TAC intrapatient variability low time in therapeutic range (TTR) have been associated with risk de novo donor–specific antibodies (dnDSA). In this study, we hypothesized that coefficient variation (CV) a result TTR rather than itself. Methods. We analyzed dnDSA, acute...
Abstract Background Risk prediction models for time-to-event outcomes play a vital role in personalized decision-making. A patient’s biomarker values, such as medical lab results, are often measured over time but traditional ignore their longitudinal nature, using only baseline information. Dynamic incorporates information to produce updated survival predictions during follow-up. Existing methods dynamic include joint modeling, which suffers from computational complexity and poor performance...
All incident cases of microscopically confirmed lung cancer diagnosed between 1974 and 1981 in western Washington State were identified through the Surveillance, Epidemiology, End Results Program National Cancer Institute, Bethesda, MD. The incidence by histologic type was studied relation to time, with age, sex, stage disease at diagnosis being taken into account. Overall within each adenocarcinoma has increased significantly since 1974. rate increase been higher among females (86%...
Background: Improved outcomes for severe sepsis and septic shock have been consistently observed with implementation of early best practice intervention strategies or the 6-hour resuscitation bundle (RB) in single-center studies. This multicenter study examines in-hospital mortality effect GENeralized Early Sepsis Intervention Strategies (GENESIS) when utilized community tertiary care settings. Methods: was comprised 2 to assess treatment. The first a prospective before-and-after...
<h3>Importance</h3> There exist limited outcomes data for women and minorities after contemporary percutaneous coronary intervention (PCI). <h3>Objective</h3> To examine 1-year in vs white men PCI with everolimus-eluting stents. <h3>Design, Settings, Participants</h3> The PLATINUM Diversity study was a single-arm enrolling minorities. Patient-level pooling the PROMUS Element Plus Post-Approval Study prespecified. Data on social determinants of health language were collected cohort, which...