- Genomics, phytochemicals, and oxidative stress
- COVID-19 Clinical Research Studies
- Eicosanoids and Hypertension Pharmacology
- Cutaneous Melanoma Detection and Management
- Long-Term Effects of COVID-19
- Sarcoma Diagnosis and Treatment
- Sulfur Compounds in Biology
- Fatty Acid Research and Health
- SARS-CoV-2 and COVID-19 Research
- Inflammatory mediators and NSAID effects
- Soft tissue tumor case studies
- Melanoma and MAPK Pathways
- Prostate Cancer Treatment and Research
- Cardiac Structural Anomalies and Repair
- Autoimmune Bullous Skin Diseases
- Immunotherapy and Immune Responses
- Bipolar Disorder and Treatment
- Dialysis and Renal Disease Management
- Systemic Sclerosis and Related Diseases
- Soft tissue tumors and treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Metabolism and Genetic Disorders
- Liver Disease and Transplantation
- Urologic and reproductive health conditions
- Biomarkers in Disease Mechanisms
Massachusetts General Hospital
2021-2024
Harvard University
2021-2024
University of California, Davis
2024
Brigham and Women's Hospital
2024
University of Pittsburgh
2015-2020
West Virginia University
2017
University of Delaware
2012-2016
Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe3+), is desensitized to NO and limits cGMP production needed for downstream activation of protein kinase G-dependent signaling blood vessel dilation.Although reactive oxygen species are known oxidize the sGC basic mechanism(s) governing iron recycling NO-sensitive, reduced remain poorly understood.Oxidant challenge studies show that vascular smooth muscle cells have an intrinsic ability reduce form protein-protein complexes...
Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitro-conjugated (NO2-CLA). Herein, NO2-CLA generation demonstrated within context acute inflammatory responses both in vitro and vivo. Macrophage activation resulted dose- time-dependent CLA also production secondary electrophilic non-electrophilic derivatives. Both exogenous as well that generated situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory...
Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD fatal COVID-19 distinct from other causes remains unknown. Objective: To compare lung parenchymal vascular alterations between pneumonia DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted consecutive (n = 20) failure histologic 21;...
Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from and maintained in a reduced state glutathione reductase (GR). Nitro oleic acid (NO2-OA) an fatty formed under digestive inflammatory conditions that both reacts with GSH induces its synthesis upon activation of Nrf2 signaling. The effects NO2-OA on homeostasis were evaluated. In addition...
The Androgen Receptor (AR) remains the leading target of advanced prostate cancer therapies. Thiosalicylamide analogs have previously been shown to act in cells as acyltransfer catalysts that are capable transferring cellular acetate, presumably from acetyl-CoA, HIV NCp7. Here we explore if acetyl-transfer activity thiosalicylamides can be redirected other targets guided by ligands for AR. We constructed conjugates and AR-binding small molecule tolfenamic acid, which binds BF-3 site AR,...
Lithium (Li) is the mainstay pharmacotherapeutic mood stabilizer in bipolar disorder. Its efficacious use complicated by acute and chronic renal side effects, including nephrogenic diabetes insipidus (NDI) progression to kidney disease (CKD). The nuclear factor erythroid-derived 2-related 2 (Nrf2) pathway senses coordinates cellular responses oxidative electrophilic stress. Here, we identify that graded genetic activation of Nrf2 protects against Li-induced NDI (Li-NDI) volume wasting via an...
Morphea is an immune-mediated fibrosing skin disorder of the dermis and subcutaneous fat with unclear pathogenesis triggers. Combinations genetic environmental factors leading to immune dysregulation are likely involved. Here, we describe a case generalized morphea profunda occurring after SARS-CoV-2 infection, discuss possible causality pathogenesis.
Abstract Mucosal melanoma (MM) is a rare subtype of with an aggressive clinical course. In cutaneous (CM), the absence pigmentation and presence NRAS/KRAS mutations are biomarkers indicating course shorter overall survival. Similar data for MM missing. We present real‐world outcome in cohort genotyped patients assessed prognostic relevance pigmentation‐ mutation status. correlated pathological reports survival MM. Furthermore, we performed clinically integrated molecular genotyping analyzed...
Erythrasma is a prevalent superficial bacterial infection typically caused by Corynebacteria species and preferentially affecting intertriginous sites including axillary, interdigital, inguinal skin folds. However, erythrasma of the vulva uncommon, with only 2 cases previously reported. Although can be diagnosed clinically using Woods lamp examination, it may not always considered in differential diagnosis for patients presenting persistent vulvar pruritus. We report 12 identified...
A 76-year-old man with a history of chronic back pain presented dizziness and altered mental status. Laboratory evaluation identified anion-gap metabolic acidosis. Additional diagnostic tests were performed.
Synovial sarcomas are high-grade soft tissue of primitive mesenchymal origin which defined by a pathognomonic t(X;18)(p11,q11) translocation, and occur in pediatric adult populations. Herein we report case 33-year-old female with history nasopharyngeal carcinoma status post radiotherapy, presenting poorly differentiated synovial sarcoma the nasal cavity arising radiation field. While development radiation-associated is known complication to date only 10 cases have been reported previously...
Background Mucosal melanoma (MM) is a rare, aggressive subtype of with limited therapeutic options and dismal clinical outcome. Systemic treatments predictive biomarkers for MM are missing the gold standard complete surgical resection. Diagnosis can be challenging, especially when pigmentation in suspicious lesions absent. The prognostic value has not been assessed.
Anti‐androgens are the gold standard of care for treatment advanced prostate cancer (PCa). The purpose this study was to characterize novel anti‐androgens PLM1, PLM6, and PAN52 designed synthesized in Koh laboratory. PLM6 but not PLM1 thought have unique mechanisms action based on their ability evade progression anti‐androgen resistance vitro. Western blot analysis nuclear fractions showed correlation between prevention AR translocation cell lines. Some differences localization effects were...
Anti‐androgens are the gold standard of care for treatment advanced prostate cancer (PCa). The purpose this study was to assess novel anti‐androgens PLM1, PLM6, and PAN52 designed synthesized in Koh laboratory. These compounds based on clinical bicalutamide, but have expanded aryl sulfonyl moieties. PLM6 PAN52, not thought unique mechanisms action their ability evade progression anti‐androgen insensitivity vitro. Prevention androgen receptor (AR) nuclear translocation found correlate with...
To the Editor: On March 11, 2020, World Health Organization elevated coronavirus disease 2019 (COVID-19) to global pandemic status. Systems-level changes in governance, health care resource allocation, and social-behavioral norms developed worldwide efforts reduce viral spread. An unintended consequence of these was a disruption routine preventative practice, leading delay or deferral diagnostic evaluation therapy across multiple disciplines.1Bhatt A.S. Moscone A. McElrath E.E. et al.Fewer...
Background: Clinical and radiologic studies investigating Coronavirus disease 2019 (COVID-19) indicate that a possible cause of severe hypoxia is marked ventilation-perfusion (VA/Q) mismatch. Published histopathology reports diffuse alveolar damage (DAD) in fatal COVID-19 indistinguishable from other causes DAD. We compared lung parenchymal vascular alterations between DAD etiologies using multidimensional approach.Methods: This autopsy cohort consisted consecutive patients (n=20) with...