A5081797786- Liver Disease Diagnosis and Treatment
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Wound Healing and Treatments
- Lipid metabolism and biosynthesis
- Dermatology and Skin Diseases
- Nail Diseases and Treatments
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Asthma and respiratory diseases
- Pressure Ulcer Prevention and Management
- Plant Pathogens and Fungal Diseases
- Allergic Rhinitis and Sensitization
- Ubiquitin and proteasome pathways
- Gut microbiota and health
- interferon and immune responses
- Diabetic Foot Ulcer Assessment and Management
- Acute Myeloid Leukemia Research
- Viral Infections and Immunology Research
- Genomics and Chromatin Dynamics
- Fungal Biology and Applications
- Bacterial Identification and Susceptibility Testing
- HIV Research and Treatment
- Liver Disease and Transplantation
- Click Chemistry and Applications
University of Wisconsin–Madison
2020-2025
National Institutes of Health
2019-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2019-2024
St. Olaf College
2014-2018
Howard Hughes Medical Institute
2012-2017
University of Michigan
2011-2017
Forma Therapeutics (United States)
2017
Harvard University Press
2014
La Trobe University
1983
Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase, and targeting the MLL1 enzymatic activity has been proposed as novel therapeutic strategy for treatment of acute harboring fusion proteins. The MLL1/WDR5 protein-protein interaction essential activity. In present study, we designed large number peptidomimetics to target based upon -CO-ARA-NH-, minimum binding motif derived from MLL1. Our study led design high-affinity peptidomimetics, which bind WDR5 with K(i)...
We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) block WDR5-mixed lineage leukemia (MLL) protein-protein interaction. Compound 18 (MM-589) binds WDR5 with an IC50 value 0.90 nM (Ki <1 nM) inhibits MLL H3K4 methyltransferase (HMT) activity 12.7 nM. potently selectively cell growth in human lines harboring translocations is >40 times better than previously reported compound MM-401. Cocrystal structures 16 complexed...
Abstract Slough is a well‐known feature of non‐healing wounds. This pilot study aims to determine the proteomic and microbiologic components slough as well interrogate associations between wound healing. Ten subjects with slow‐to‐heal wounds visible were enrolled. Aetiologies included venous stasis ulcers, post‐surgical site infections pressure ulcers. Patient co‐morbidities healing outcome at 3‐months post‐sample collection was recorded. Debrided analysed microscopically, through untargeted...
MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and promising new cancer therapeutic target. The catalytic activity of regulated by the formation core complex consisting MLL1, WDR5, RbBP5, Ash2L. interaction between WDR5 plays an essential role in regulation H3K4 targeting this using small molecules may represent attractive strategy. In study, we have defined elements required for its high-affinity binding to WDR5. Our data showed that minimal crucial are -CO-ARA-NH- motif two...
Alcoholic fatty liver disease (AFLD) is characterized by an abnormal accumulation of lipid droplets (LDs) in the liver. Here, we explore composition hepatic LDs a rat model AFLD. Five to seven weeks alcohol consumption led significant increases triglyceride mass, along with LD number and size. Additionally, from rats early alcoholic injury show decreased ratio surface phosphatidylcholine (PC) phosphatidylethanolamine (PE). This occurred parallel increase association perilipin 2, prominent...
Incomplete antiseptic efficacy against potentially pathogenic microbial taxa places some patients at disproportionate risk for developing a surgical site infection. Laboratory models capable of interrogating the effects antiseptics on skin and its complex communities are desperately needed to improve better tailor formulations. This work aims establish an ex vivo porcine model explore impact topical superficial lipids. Microbiome samples were treated with propidium-monoazide selectively...
ABSTRACT Broad-spectrum antiseptics such as chlorhexidine gluconate (CHG) have widespread use pre-surgical tools to lower skin microbial burden and reduce the risk of surgical site infection. However, short- long-term effects CHG on healthy communities remain undefined due confounding binding with persistent bacterial DNA surface. Here, we aim accurately characterize immediate impact preparation CHG-based human microbiome. Twenty-eight patients undergoing elective surgeries were enrolled....
Abstract Background and Aim Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little understood about immune responses to HDV. This study aims characterize systemic environments of hepatitis B (HBV) HDV patients at various disease stages. Methods A total 129 subjects were evaluated: 53 HBV, 43 HDV, 33 healthy controls. HBV categorized by aspartate aminotransferase platelet ratio index (APRI) into mild (APRI < 0.5), moderate, severe > 1.0)....
Human papillomaviruses (HPVs) are the most common sexually transmitted infection in United States and a major etiological agent of cancers anogenital tract oral cavity. Growing evidence suggests changes host microbiome associated with natural history ultimate outcome HPV infection. We sought to define cervicovaginal during papillomavirus infection, persistence, pathogenesis using murine (MmuPV1) model. Cervicovaginal lavages were performed over time course MmuPV1 immunocompetent female
Bile acids mediate gut-liver cross-talk through bile acid receptors. Serum, hepatic, and microbial metabolism was evaluated in HCV-compensated chronic liver disease.
Abstract Surgical site infections (SSI) continue to occur despite widespread adoption of surgical antiseptics. The effects chlorhexidine gluconate (CHG)-based antiseptics on the skin microbiome also remains undefined due confounding CHG persistence skin. Patients undergoing elective surgery were enrolled characterize immediate and long-term impact pre-surgical preparation with antiseptic microbial communities. Due broad-spectrum antimicrobial activity its propensity bind extracellular DNA,...
Abstract Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, β-D-glucan in addition their pattern recognition receptors degree hepatic macrophage uptake. The findings suggest that regulation serum peptidoglycan differs from lipopolysaccharide. Additionally, activation the liver may be...
Abstract Porcine models are frequently used for burn healing studies; however, factors including anatomic location and lack of standardised wound methods can impact the interpretation data. The objectives this study to examine influence anatomical locations on uniformity creation in porcine models. To optimise parameters dorsal ventral surfaces, ex vivo situ euthanized animals were first location‐dependence depth contact time relationship. location‐dependent was then examined using...
From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing screen blood of deceased enterocolitis-positive for viruses. In five out eight enterocolitis, we discovered a novel pegivirus not present in ten matched, clinically normal controls. The virus, which named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide...
Abstract Background Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. MT has yet to be completely defined in chronic hepatitis B (HBV) and D (HDV). Aim To characterize immune response HBV HDV at various stages of disease. Methods Serum from 53 HBV, 43 HDV, 36 healthy control (HC) subjects was obtained. Subjects were categorized by aspartate aminotransferase platelet ratio index mild (&lt;0.5), moderate, severe (&gt;1.0)...
TSLP is a newly‐identified cytokine thought to be involved in airway inflammation. levels have been shown significantly increase smooth muscle (ASM) with chronic obstructive pulmonary disease and other inflammatory diseases. This study evaluated the expression of human ASM cells tissues exposed cigarette smoke extract (CSE) or pro‐inflammatory cytokines TNF‐α IL‐13. In parallel studies, was house dust mite sensitized mice without exposure. The presence TSLP‐receptors were verified using...
Abstract Background & Aims Direct‐acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA is common, little known about intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of gut microbiome and liver SVR. Methods Twenty‐two HCV patients were evaluated before 9 months 12 weeks sofosbuvir/velpatasvir treatment. All achieved A biopsy, portal blood (direct vein cannulation),...
Abstract Slough is a well-known feature of non-healing wounds. This study aims to determine the proteomic and microbiologic components slough as well interrogate associations between wound healing. Twenty-three subjects with slow-to-heal wounds visible were enrolled. Etiologies included venous stasis ulcers, post-surgical site infections, pressure ulcers. Patient co-morbidities healing outcome at 3-months post-sample collection was recorded. Debrided analyzed microscopically, through...
The skin and its microbiome function to protect the host from pathogen colonization environmental stressors. In this study, using Wisconsin Miniature Swine model, we characterize porcine fungal bacterial microbiomes, identify isolates displaying antifungal activity, use whole-genome sequencing biosynthetic gene clusters encoding for secondary metabolites that may be responsible antagonistic effects on fungi. Through comprehensive approach of paired with culturomics, report discovery novel...