A5070937968- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- Gut microbiota and health
- Asthma and respiratory diseases
- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Adrenal Hormones and Disorders
- Genetic factors in colorectal cancer
- Plant Genetic and Mutation Studies
- Pharmacogenetics and Drug Metabolism
- Breast Cancer Treatment Studies
- CAR-T cell therapy research
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Single-cell and spatial transcriptomics
- Estrogen and related hormone effects
- MicroRNA in disease regulation
- Respiratory and Cough-Related Research
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
Cleveland Clinic Lerner College of Medicine
2019-2025
Cleveland Clinic
2019-2024
Cerner (United States)
2021-2024
Kuwait University
2012
University of Michigan
2012
University of Toledo
2007-2012
University of Connecticut
2012
University of Toledo Medical Center
2008
Marquette University
2006-2007
Epigenetic modifications such as histone methylation play an important role in human cancer metastasis. Enhancer of zeste homolog 2 (EZH2), which encodes the methyltransferase component polycomb repressive complex (PRC2), is overexpressed widely breast and prostate cancers epigenetically silences tumor suppressor genes. Expression levels novel metastasis Raf-1 kinase inhibitor protein (RKIP) have been shown to correlate negatively with those EZH2 cell lines well clinical tissues. Here, we...
Abstract Epithelial ovarian cancer (EOC) is the leading cause of gynecologic death. Despite initial responses to intervention, up 80% patient tumors recur and require additional treatment. Retrospective clinical analysis patients with indicates antibiotic use during chemotherapy treatment associated poor overall survival. Here, we assessed whether (ABX) would impact growth EOC sensitivity cisplatin. Immunocompetent or immunocompromised mice were given untreated control ABX-containing...
Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied human airways.Objectives: To measure whether and its ligands associated with asthma outcomes.Methods: We compared the effects of expression on lung function, symptom scores, fractional exhaled nitric oxide (FeNO) adults enrolled SARP (Severe Asthma Research Program). The impact sex androgens outcomes was also evaluated validation studies Cleveland Clinic Health System NHANES (U.S....
Significance Although resistance to glucocorticoids is a major clinical problem, the underlying mechanisms are unknown. It known that glucocorticoid use can suppress adrenal androgen production. In population studies, animal models, and cell culture experiments, androgens associated with several benefits in asthma, but neither glucocorticoid-resistant asthma nor genetic determinants of responsiveness have been studied humans. A missense-encoding variant HSD3B1 regulate conversion from...
Background/Objectives: Macrophages play a pivotal role in various pathogenic processes, necessitating the development of efficient differentiation techniques to meet high demand for these cells research and therapy. Human macrophages can be obtained via culturing peripheral blood monocytes; however, this source has limited yields requires patient contact each proposed use. In addition, it would difficult perform gene editing on monocytes. The objectives study are define robust consistent...
Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity mortality in patients with chronic obstructive pulmonary disease (COPD). The severity sarcopenia COPD is variable, there are limited data explain phenotype heterogeneity. Others have shown that several hallmarks cellular senescence, a potential mechanism primary (age-related) sarcopenia. We tested if genetic contributors the variability sarcopenic accelerated senescence COPD.
Background Trimethylamine-N-oxide (TMAO) is a small molecule derived from the metabolism of dietary nutrients by gut microbes and contributes to cardiovascular disease. Plasma TMAO increases following consumption red meat. This metabolic change thought be partly because expansion able use abundant in Methods Results We used data randomized crossover study estimate degree which can estimated fecal microbial composition. Healthy participants received series 3 diets that differed protein source...
Cytochrome P450 2D6 (CYP2D6) is used to develop an approach for predicting affinity and relevant binding conformation(s) highly flexible sites. The combines the use of docking scores compound properties as attributes in building a neural network (NN) model. It begins by identifying segments CYP2D6 that are important specificity, based on structural variability among diverse CYP enzymes. A family distinct, low-energy conformations generated using simulated annealing (SA) collection 82...
Background We sought to determine whether mitochondrial DNA (mtDNA) content can be used as markers for 12 key phenotypes among cardiovascular disease patients, and these are valid across patients with diverse ancestries. Methods Results was collected from the peripheral blood of 996 at Cleveland Clinic. The mtDNA copy number DNA-level variation were assessed whole-genome sequence. Patients also ascertained retrospectively histories 10 clinical events, well maximum stenosis extent baseline....
BACKGROUND. Genetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common White populations, functionally adrenal permissive increases the aromatase substrate androstenedione. We hypothesized that homozygous inheritance adrenal-permissive HSD3B1(1245C) associated with postmenopausal receptor–positive (ER-positive) cancer.
Abstract Glucocorticoids are a highly effective first-line treatment option for many inflammatory diseases, including asthma. Some patients develop steroid-resistant condition, yet, the cellular and molecular mechanisms underlying steroid resistance remain largely unknown. In this study, we used murine model of airway inflammation report that combining systemic dexamethasone intranasal IL-27 is able to reverse inflammation. Foxp3+ regulatory T cells (Tregs) were required during...
Seizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, electrophysiological variables. In this pilot study, we investigated whether genetic molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response surgery.Post-operative seizure-outcomes were collected at last follow-up (>6 months) 201 adult patients DRE who underwent...
Breast cancer is the most common in females, affecting one every eight women and accounting for majority of cancer-related deaths worldwide. Germline mutations BRCA1 BRCA2 genes are significant risk factors specific subtypes breast cancer. associated with basal-like cancers, whereas luminal-like disease. Defects mammary epithelial cell differentiation have been previously recognized germline BRCA1/2 mutation carriers even before incidence. However, underlying mechanism largely unknown. Here,...
Abstract Objective Memory dysfunction is prevalent in many neurological disorders and can have a significant negative impact on quality of life. The genetic contributions to memory impairment epilepsy, particularly temporal lobe epilepsy (TLE), remain poorly understood. Here, we compare the brain transcriptome between TLE patients with without verbal impairments identify genes signaling networks important for episodic memory. Methods Brain tissues were resected from 23 adults who underwent...
Since their discovery ~70 years ago, glucocorticoids (GC) have been widely used to elicit a systemic anti-inflammatory response, and currently play major role in the treatment of asthma other inflammatory diseases (1). However, unresponsiveness GC some individuals is limitation asthma, mechanisms underlying this clinical entity are not fully elucidated Indeed, severe generally defined as that remains symptomatic despite high-dose inhaled and/or therapy. GCs inhibit production adrenal...
Abstract Background The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes castration-resistant prostate cancer is associated with estrogen receptor positivity in postmenopausal breast cancer. Like cancer, endometrial another malignancy hormone-dependent hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate Methods employed a previously...