A5003164186- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Sarcoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Kruppel-like factors research
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Dermatology and Skin Diseases
- Ophthalmology and Visual Health Research
- Immune Cell Function and Interaction
- Berberine and alkaloids research
- Immunotherapy and Immune Responses
- History of Medicine Studies
- Cancer-related gene regulation
- Alkaloids: synthesis and pharmacology
- Renal cell carcinoma treatment
- Cardiac tumors and thrombi
- Eosinophilic Disorders and Syndromes
- Drug-Induced Adverse Reactions
- Mycobacterium research and diagnosis
- Peptidase Inhibition and Analysis
- Autoimmune Bullous Skin Diseases
The Ohio State University Wexner Medical Center
2023-2025
Northwestern University
2024
The Ohio State University
2017-2024
Nationwide Children's Hospital
2016-2018
Center for Cancer and Blood Disorders
2018
University of Utah
2012-2017
Huntsman Cancer Institute
2012-2014
Significance Ewing sarcoma is a pediatric bone malignancy driven by the fusion protein EWS/FLI. EWS/FLI mediates oncogenesis through its role as an aberrant transcription factor, but little known about molecular mechanisms underlying this function. We demonstrate in cells that activates gene targets binding at associated GGAA-microsatellites, and these repetitive sequences are necessary for cell proliferation anchorage-independent growth. Furthermore, we show previously unknown EWS portion...
Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI chromosomal translocation. The resulting fusion protein an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate repress thousands target genes mediating oncogenesis. However, mechanisms interaction with microsatellites regulation gene expression not clearly understood. Here, we profile genome-wide binding expression. Using combination...
Multi-agent chemotherapeutic regimes remain the cornerstone treatment for Ewing sarcoma, second most common bone malignancy diagnosed in pediatric and young adolescent populations. We have reached a therapeutic ceiling with conventional cytotoxic agents, highlighting need to adopt novel approaches that specifically target drivers of sarcoma oncogenesis. As KDM1A/lysine-specific demethylase 1 (LSD1) is highly expressed cell lines tumors, elevated expression levels associated worse overall...
Quality of life has not been well-explored in patients hospitalized with morbilliform drug eruptions. We found that eruptions impacted across six major domains: impact on other medical conditions, self-image, distrust, diet, mental health, and physical symptoms. Dermatologists healthcare providers should remain cognizant the domains counseling management this patient population.
Background The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites highly polymorphic humans, preliminary evidence suggests EWS/FLI-mediated expression is dependent on the number of GGAA motifs within microsatellite. Objectives Here we sought to examine spectrum a NR0B1 promoter (a critical target) primary tumors,...
Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions Ewing sarcoma prime example this, resulting potent chimeric oncoproteins biological properties and transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, most common sarcoma, upregulates gene expression...
In-transit metastases of malignant melanoma pose a significant clinical challenge, particularly in patients with contraindications to systemic therapies. While surgical excision and immunotherapies remain standard treatments, localized therapies such as intralesional talimogene laherparepvec (T-VEC) topical imiquimod, which stimulate tumor-specific T-cell responses, have garnered increasing attention for their potential efficacy tolerability. Although the individual these is well-documented,...
Abstract The management of alopecia areata (AA) in pediatric patients poses unique challenges, particularly regarding treatment discussions and decision making involving both their families. This commentary presents findings from unpublished research on treatment‐discontinuation between AA treating providers, shedding light the hopes, expectations, disappointments individuals with severe AA. study explored patient guardian satisfaction these discussions, emphasizing importance addressing...
BACKGROUND Deep learning has been used to classify basal cell carcinoma (BCC) on histopathologic images. Segmentation models, required for localization of tumor Mohs surgery (MMS) frozen section slides, have yet reach clinical utility. OBJECTIVE To train a segmentation model localize BCC MMS slides and evaluate performance by subtype. MATERIALS AND METHODS The study included 348 fresh tissue scanned as whole slide images, from patients treated with BCC. foci were manually outlined using the...
Abstract Carney complex is a rare genetic disorder associated with number of cutaneous lesions, especially myxomas. We present case myxoma (superficial angiomyxoma) trichofolliculoma‐like features in patient complex, and explore how the histopathology provides critical context for elucidating etiology this benign neoplasm.
Eye exams, specifically of the retina, are often underutilized by clinicians in treating patients with diseases that have eye manifestations. This is due, part, to inherent difficulty learning use a direct ophthalmoscope. Currently, instructor and student not able simultaneously visualize retina. Recent investigations introduced devices incorporate smartphone, which could facilitate teaching allows storage images from exam. Although incorporating smartphone provides ability track progression...
Abstract The purpose of this study is to investigate how EWS/FLI transcriptionally activates gene targets via polymorphic GGAA microsatellites. Ewing Sarcoma a pediatric bone malignancy initiated by t(11;22) chromosomal translocation that produces the oncoprotein. and represses its target genes mediate oncogenic reprogramming. Expression up-regulated correlates with binding associated These microsatellites show length polymorphisms, suggesting microsatellite polymorphisms may have critical...
<p>Cytotoxic effects of the irreversible KDM1A inhibitors GSK-LSD1 and Tranylcypromine</p>
<p>Targeted KDM1A inhibition and EWS/FLI knockdown induces similar transcriptional signatures</p>
<p>Protein expression of ER-stress response genes following treatment with SP-2509</p>
<p>Validation of KDM1A knockdown in Ewing sarcoma cells</p>
<p>GSK-LSD1, Doxorubicin and AraC have no effect on KDM1A KDM1B expression</p>
<p>Hypersensitive SP-2509 cell lines display similar transcriptomic profiles</p>
<div>Abstract<p>Multi-agent chemotherapeutic regimes remain the cornerstone treatment for Ewing sarcoma, second most common bone malignancy diagnosed in pediatric and young adolescent populations. We have reached a therapeutic ceiling with conventional cytotoxic agents, highlighting need to adopt novel approaches that specifically target drivers of sarcoma oncogenesis. As KDM1A/<u>l</u>ysine-<u>s</u>pecific <u>d</u>emethylase 1 (LSD1) is highly...