A5039383862- HIV-related health complications and treatments
- HIV Research and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Extracellular vesicles in disease
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- interferon and immune responses
- Pulmonary Hypertension Research and Treatments
- RNA modifications and cancer
- Kawasaki Disease and Coronary Complications
- Cell Adhesion Molecules Research
- Adipokines, Inflammation, and Metabolic Diseases
- SARS-CoV-2 and COVID-19 Research
- Cardiovascular Disease and Adiposity
- Systemic Lupus Erythematosus Research
- Inflammasome and immune disorders
- Lipoproteins and Cardiovascular Health
- Protease and Inhibitor Mechanisms
- COVID-19 Clinical Research Studies
- Influenza Virus Research Studies
- Hepatitis C virus research
- Computational Drug Discovery Methods
- Long-Term Effects of COVID-19
- Cell Image Analysis Techniques
Brigham and Women's Hospital
2020-2025
Harvard University
2020-2025
Indiana University Indianapolis
2023
Indiana University – Purdue University Indianapolis
2015-2023
Indiana University School of Medicine
2015-2021
Indiana University
2018-2021
University School
2019-2020
Richard L. Roudebush VA Medical Center
2018-2019
Signature Research (United States)
2018
Cellular heterogeneity of aortic valves complicates the mechanistic evaluation calcification processes in calcific valve disease (CAVD), and animal models are lacking. In this study, we identify a disease-driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided omic profiling, network-based characterize DDP fingerprint as CD44highCD29+CD59+CD73+CD45low discover potential key regulators human CAVD. These DDP-VICs demonstrate...
Interferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits vitro exploration proinflammatory mechanisms and the development novel immune therapies. We hypothesized that study macrophage subpopulations could lead to anti-inflammatory interventions.
It remains a mystery why HIV-associated end-organ pathologies persist in the era of combined antiretroviral therapy (ART). One possible mechanism is continued production HIV-encoded proteins latently HIV-infected T cells and macrophages. The proapoptotic protein HIV-Nef persists blood ART-treated patients within extracellular vesicles (EVs) peripheral mononuclear cells. Here we demonstrate that present EVs isolated from BAL on ART. We hypothesize persistence lung induces endothelial...
Vein graft failure remains a common clinical challenge. We applied systems approach in mouse experiments to discover therapeutic targets for vein failure.Global proteomics and high-dimensional clustering on multiple tissues were used identify potential pathogenic mechanisms. The PPARs (peroxisome proliferator-activated receptors) pathway served as an example substantiate our discovery platform. In vivo with macrophage-targeted PPARα small interfering RNA, or the novel, selective activator...
Lipoprotein(a) (Lp[a]) blood levels >50 mg/dL is a major cardiovascular disease risk factor in humans. Lp(a) associates with increased calcification, critical pathology no clinically available drug therapies. The mechanisms through which increases calcification remain undefined. We hypothesized that promotes the release of calcifying extracellular vesicles (EVs) contribute to formation microcalcification tissues. Here, we show both primary human smooth muscle cells (SMCs) and valvular...
Rationale: Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role cardiovascular diseases. A possible cofactor may be persistence of the early response gene Nef, which we have demonstrated recently persist lungs HIV+ patients on therapy. Previously, reported that strains with but not Nef-deleted strains, cause endothelial proinflammatory activation and apoptosis. Objective: To characterize mechanisms through HIV-Nef leads development diseases using ex vivo...
Abstract The coronavirus disease (COVID-19) pandemic has occurred in Massachusetts multiple waves led by a series of emerging variants. While the evidence linked obesity with severe symptoms COVID-19, effect on susceptibility to SARS-CoV-2 infection remains unclear. Identification intrinsic factors, which increase likelihood exposed individuals succumbing productive could help plan mitigation efforts curb illness. We aim investigate whether obese have higher developing given comparable...
Conventional drug screening methods search for a limited number of small molecules that directly interact with the target protein. This process can be slow, cumbersome and has driven need developing new approaches to counter rapidly emerging diseases such as COVID-19. We propose pipeline repurposing combining in silico candidate identification followed by vitro characterization these candidates. first identified gene interest, entry receptor SARS-CoV-2 virus, angiotensin converting enzyme 2...
Abstract Calcific aortic valve disease (CAVD) is a complex cardiovascular pathology, culminating in stenosis, heart failure and premature mortality, with no comprehensive treatment strategy, except replacement. While T cells have been identified within the valve, their contribution to pathogenesis remains unclear. To elucidate heterogenous phenotype of immune populations present patients CAVD, deep phenotypic screens paired peripheral blood were conducted via flow cytometry (n=20)...
Coronavirus disease 2019 (COVID-19) is transitioning from a pandemic to an endemic phase through recurring mutations. Initial efforts focused on developing strategies mitigate infection of lung epithelial cells which are the primary targets SARS-CoV-2 virus using affinity spike protein human ACE2 receptor. SARS-CoV-2, however, infects additional cell types present in such as macrophages alternate entry receptor Neuropilin 1 (NRP1). Developing novel therapeutic prevent crucial for...
Background: Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause death morbidity worldwide. Our previous study recognized ADP-ribosylation, post-translational modification, as novel regulator macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role in atherogenesis. hypothesized that ADP-ribosylated proteins circulate from liver, accumulate...
Background: People living with HIV (PLWH) on anti-retroviral therapy remain at risk for cardiovascular diseases, including atherosclerosis. We hypothesized that persistent viral protein (HIV-Nef) in extracellular vesicles (EVs) modulate macrophage heterogeneity to impair atheroprotective efferocytosis accelerate disease. Methods and Results: Macrophage was characterized human primary macrophages (50,931 cells; 4 donors) stimulated EVs engineered contain HIV-Nef by simultaneous scRNAseq...
Background: The aberrant activation of the NLRP3 inflammasome in macrophages promotes chronic inflammation cardiovascular disease (CVD). NEK7 is essential to inflammasome’s function, however, its role inflammasome-mediated macrophage has yet be elucidated. Methods&Results: We employed CRISPR/Cas9 gene editing delete human primary cells (PBMCs) and a macrophage-like cell line (THP-1). First, we mass spectrometry-based proteomics monitor response Scramble control (ΔScr) or NEK7-null...
Background: Chronic kidney disease (CKD) is a global burden with high unmet medical needs. Despite the availability of potent drugs such as statins, CKD patients have accelerated atherogenesis and succumb to vascular complications. Underlying mechanisms, however, remain unclear. Elevated levels major uremic toxin, indoxyl sulfate (IS), an independent cardiovascular risk factor in patients. Using multi-layer systems approach followed by vitro vivo experiments, we investigated mechanisms which...
Background: To address how cardiovascular disease is increased in HIV patients with and without therapy, we have tested the effects of HIV-infected T cell when contact to human coronary endothelial cells (HCAEC). We found that these could induce dysfunction death at a much larger extent than free virus itself. identify HIV-Nef protein, major pathogenic factor progression HIV-induced end organ disease, as mechanism for this finding. Because our finding transferred from HCAEC death, asked...