- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Atrial Fibrillation Management and Outcomes
- Immunotherapy and Immune Responses
- Cardiomyopathy and Myosin Studies
- LGBTQ Health, Identity, and Policy
- Sexuality, Behavior, and Technology
- Cardiac Arrhythmias and Treatments
- Reproductive Health and Technologies
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Viral Infections and Immunology Research
- Nitric Oxide and Endothelin Effects
- Immune Cell Function and Interaction
- Signaling Pathways in Disease
- Liver Disease and Transplantation
- Renal and related cancers
- Cardiac Fibrosis and Remodeling
- Cardiovascular Disease and Adiposity
- Genetic Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- African Sexualities and LGBTQ+ Issues
- Virus-based gene therapy research
Denver Health Medical Center
2024
University of Colorado Denver
2024
The Wistar Institute
2022-2024
University of Pennsylvania
2023-2024
University of Michigan
2009-2020
University of Colorado Anschutz Medical Campus
2020
Ironwood Pharmaceuticals (United States)
2019
Norfolk State University
2014
University of Rochester
2014
University of California, San Francisco
2012
In the absence of cell surface cancer-specific antigens, immunotherapies such as chimeric antigen receptor (CAR) T cells, monoclonal antibodies, or bispecific engagers typically target lineage antigens. Currently, are individually designed and tested for each disease. This approach is inefficient limited to a few antigens which on-target/off-tumor toxicities clinically tolerated. Here, we sought develop universal CAR therapy blood cancers directed against pan-leukocyte marker CD45. To...
Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, and fibrillation. VT caused enhanced Ca 2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial endocardial optical mapping, chemical subendocardial ablation with Lugol’s solution, patch clamping in knockin (RyR2/RyR2 R4496C ) mouse model to investigate the arrhythmogenic mechanisms catecholaminergic VT. In isolated hearts, spontaneous...
Little is known about the mechanisms underlying transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing AF we tested hypothesis that rate electric and structural remodeling, assessed by dominant frequency (DF) changes, determines time at which becomes persistent.Self-sustained was induced tachypacing. Seven sheep were euthanized 11.5±2.3 days after without reversal sinus rhythm; 7 341.3±16.7 AF. sham-operated animals in rhythm for 1 year. DF...
Rationale: Kv1.5 (KCNA5) is expressed in the heart, where it underlies I Kur current that controls atrial repolarization, and pulmonary vasculature, regulates vessel contractility response to changes oxygen tension. Atrial fibrillation hypoxic hypertension are characterized by downregulation of protein expression, as well with oxidative stress. Formation sulfenic acid on cysteine residues proteins an important, dynamic mechanism for regulation under widely reported be redox-sensitive,...
Glioblastoma multiforme (GBM) is among the most difficult cancers to treat with a 5-year survival rate less than 5%. An immunotherapeutic vaccine approach targeting GBM-specific antigen, EGFRvIII, previously demonstrated important clinical impact. However, immune escape variants were reported in trial, suggesting that multivalent approaches GBM-associated antigens may be of importance. Here we focused on vivo delivery synthetic DNA-encoded bispecific T cell engagers (DBTEs) two antigens,...
Background Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure obesity, with potentially detrimental effects on myocardial function. As major components epicardial fat, FFAs may be abnormally regulated, a potential to detrimentally modulate electro-mechanical The cellular mechanisms underlying such unknown. Objective To determine the electrophysiological palmitic (PA), stearic (SA) oleic (OA) sheep myocytes. Methods We used...
Background Advanced clear cell renal carcinoma (ccRCC) is a prevalent kidney cancer for which long-term survival rates are abysmal, though immunotherapies showing potential. Not yet clinically vetted bispecific T engagers (BTEs) that activate cell-mediated killing through intercellular synapsing. Multiple BTE formats exist, however, with limited cross-characterizations to help optimize new drug design. Here, we developed BTEs treat ccRCC by targeting carbonic anhydrase 9 (CA9) while...
Synapse-associated protein 97 (SAP97) is a scaffolding crucial for the functional expression of several cardiac ion channels and therefore proper excitability. Alterations in SAP97 can modify ionic currents underlying action potential consequently confer susceptibility arrhythmogenesis. In this study, we generated murine model inducible, cardiac-targeted Sap97 ablation to investigate arrhythmia molecular mechanisms. Furthermore, sought identify human (DLG1) variants that were associated with...
Despite advances in ovarian cancer (OC) therapy, recurrent OC remains a poor-prognosis disease. Because of the close interaction between cells and tumor microenvironment (TME), it is important to develop strategies that target engage components TME. A major obstacle development therapies identification targets with expression limited surface avoid off-target interactions. The follicle-stimulating hormone receptor (FSHR) has selective on granulosa expressed 50%-70% serous OCs. We generated...
We examined the impact of coexpressing inwardly rectifying potassium channel, Kir2.3, with scaffolding protein, synapse-associated protein (SAP) 97, and determined that coexpression these proteins caused an approximately twofold increase in current density. A combination techniques was used to determine if SAP97-induced Kir2.3 whole cell currents resulted from changes number channels membrane, unitary channel conductance, or open probability. In absence SAP97, found predominantly a...
Purpose: The study purpose was to report neovaginal dilation outcomes and identify factors associated with pain, discontinuation, sexual function for transgender individuals who underwent gender-affirming vaginoplasty. Methods: A retrospective cohort design employed of patients 18 years or older undergoing full-depth vaginoplasty pelvic floor physical therapy (PFPT) between May 2018 April 2021 at a safety-net hospital through medical record review an online survey developed patient advisory...
Synapse-associated protein 97 (SAP97) is a scaffolding and the archetypical MAGUK. In vitro studies suggest that SAP97 regulates expression of cardiac Na K channels, may be important for excitation. OBJECTIVES: To generate model inducible, targeted ablation, to investigate arrhythmia susceptibility underlying cellular/molecular mechanisms. Methods: deletion was generated using Cre-Lox system. Animals were subjected biochemistry, electrophysiology, echo- electrocardiographic analyses....