A5041170431- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Vasculitis and related conditions
- Rheumatoid Arthritis Research and Therapies
- Transplantation: Methods and Outcomes
- Single-cell and spatial transcriptomics
- Cancer-related Molecular Pathways
- IL-33, ST2, and ILC Pathways
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Protease and Inhibitor Mechanisms
- Polysaccharides and Plant Cell Walls
- Viral-associated cancers and disorders
- Protein Degradation and Inhibitors
- Statistical Methods in Clinical Trials
- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- DNA Repair Mechanisms
University of Michigan
2021-2025
Michigan Center for Translational Pathology
2024
Ann Arbor Center for Independent Living
2024
Michigan Medicine
2024
Center for Excellence in Education
2022
Thoracic Surgery Foundation
2022
American Association for Thoracic Surgery
2022
National Eye Institute
2018-2020
National Institutes of Health
2018-2020
University of Wisconsin–Madison
2016-2019
Neutrophil extracellular traps (NETs), structures composed of decondensed chromatin and antimicrobial molecules, are released in a process called NETosis. NETs, which part normal host defense, have also been implicated multiple human diseases. Unfortunately, methods for quantifying NETs limitations constrain the study disease. Establishing optimal NET quantification holds potential to further elucidate role pathologic processes. To better quantify NET-like structures, we created DNA Area...
Highlights d Cdk12 ablation induces preneoplastic prostate lesions with T cell infiltration loss mediates genomic instability through
220 Background: Prostate cancer (PC) is genetically heterogeneous, and genomic alterations may impact prognosis therapy response. We created CAPSTONE, a database of lethal PC that integrates comprehensive sequencing with deep clinical phenotyping to explore the implications castrate resistant prostate (CRPC) evolution. Methods: patients underwent tissue collection (4/05-7/21) for tumor RNA-sequencing tumor/normal whole exome (HUM00046018, HUM00048105, HUM00067928, SU2C). Sequencing was...
The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung with resultant protein citrullination may trigger anti-citrullinated antibodies, inflammation, arthritis. Alternatively, be two manifestations of a single underlying pathology. has increased TNF-α levels are high arthritis; however, it unknown if can induce citrullination. citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-α-induced arthritis, but role for PAD4 not...
Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages aging regulatory regions, some these cluster chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome....
Abstract Loss of the tumor suppressive activity protein phosphatase 2A (PP2A) is associated with cancer, but underlying molecular mechanisms are unclear. PP2A holoenzyme comprises a heterodimeric core, scaffolding A subunit and catalytic C subunit, one over 20 distinct substrate-directing regulatory B subunits. Methylation regulates heterotrimerization, affecting binding substrate specificity. Here, we report that leucine carboxy methyltransferase (LCMT1), which methylates L309 residue acts...
Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute arthritis by citrullinating histones induce neutrophil extracellular traps (NETs), which display that targeted autoantibodies drive inflammation and Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, However, PAD4's role in human is less clear. Here, we determine if...
Biallelic loss of cyclin-dependent kinase 12 (
ABSTRACT Background and Aims The intestine plays a key role in metabolism, nutrient water absorption, provides both physical immunological defense against dietary luminal antigens. protective mucosal lining the is critical component of intestinal barrier that when compromised, can lead to increased permeability, defining characteristic inflammatory bowel disease (IBD), among other diseases. Here, we define new for flavin-containing monooxygenase (FMO) family enzymes maintaining healthy...
Introduction & Objective: Insulin Resistance (IR) is heritable and predisposes to cardiometabolic disease, but few causes are known due limited samples with direct measures of IR. Methods: To increase power identify IR-associated loci we carried out a genome wide association study (GWAS) an indirect marker IR, the triglyceride high-density lipoprotein cholesterol ratio (TG:HDL-C) adjusted for BMI (TG:HDL-C adj BMI) in UK Biobank (N=401,090). We used mixed linear model controlling age,...
263 Background: Prostate cancer (PCa) is characterized by considerable genetic heterogeneity, and complex genomic features may influence prognosis treatment response. We created a database of aggressive PCa that integrates comprehensive sequencing with detailed clinical outcomes to better understand the optimal use sequencing. Methods: From 4/2005-7/2021, patients older than 18 years age underwent tissue collection for tumoral RNA-sequencing tumor/normal whole exome at our institution...
ABSTRACT Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity the microbiota. role of metabolite in development, progression, treatment resistance is unclear. We generated an autochthonous metastatic mouse model unbiased multi-omic analyses this reveals a robust accumulation tumoral ammonia. high ammonia levels induce T cell reprogramming, increase...
Abstract Introduction: Chromosomal instability (CIN) is a continuum of chromosomal gains and losses present in tumor cells. While increasing CIN linked to poor patient outcomes select cancers, the prognostic significance CIN, its association with molecular phenotypes therapeutic response advanced prostate cancer (PCa) poorly understood. We characterize aggressive Pca by integrating DNA/RNA sequencing detailed clinical information. Methods: From 4/2005-7/2021, 290 men PCa underwent...
Abstract Introduction Key barriers restrict the utility (or use) of genetic information in making treatment decisions metastatic PCa. First, lack platforms that link genomic and clinical outcome data limits our ability to uncover clinico-genomic associations. Second, predictions based on univariate biomarkers (e.g. individual mutations), are insufficient given heterogeneity genomes. Third, predictive for standard therapies use testing prioritize patients trials. We initiated CAPSTONE, a...