A5038202787- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- CAR-T cell therapy research
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Immune Response and Inflammation
- S100 Proteins and Annexins
- Neurogenetic and Muscular Disorders Research
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- Metal complexes synthesis and properties
- Nerve injury and regeneration
- Inflammation biomarkers and pathways
- Genetics and Neurodevelopmental Disorders
- Lymphatic System and Diseases
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Neurological Complications and Syndromes
- Histone Deacetylase Inhibitors Research
- Neuroblastoma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Hereditary Neurological Disorders
Children's Hospital of Philadelphia
2023-2025
University of Pennsylvania
2025
UConn Health
2013-2018
University of Connecticut
2015-2016
Jewish General Hospital
2012-2013
McGill University
2011-2012
The brain's initial innate response to stroke is primarily mediated by microglia, the resident macrophage of CNS. However, as early 4 h after stroke, blood–brain barrier compromised and monocyte infiltration occurs. lack discriminating markers between these two myeloid populations has led many studies generate conclusions based on grouping populations. A growing body evidence now supports distinct roles played microglia monocytes in disease models. Using a flow cytometry approach, combined...
The peripheral immune system plays a critical role in aging and the response to brain injury. Emerging data suggest inflammatory responses are exacerbated older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences composition circulating infiltrating leukocytes recruited old male mice after stroke compared young mice. Blood neutrophilia neutrophil invasion into were increased aged animals. Relative...
Aging is associated with an increase in basal inflammation the CNS and overall decline cognitive function poorer recovery following injury. Growing evidence suggests that leukocyte recruitment to also increased normal aging, but, date, no systematic evaluation of these age-associated leukocytes has been performed. In this work, effect aging on was examined. more CD45(high) leukocytes, primarily composed conventional CD8(+) T cells. These results were strain independent seen both sexes....
Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and developing therapies. SPG4, most common form HSP, is caused by autosomal dominant mutations SPAST gene, which encodes microtubule-severing ATPase spastin. Here, we have generated a human model SPG4 establishing induced pluripotent stem cells (iPSCs) from an patient differentiating these into telencephalic...
The presence of tumor-infiltrating CD8(+) T cells is associated with tumor regression and better prognosis. Cytomegalovirus (CMV) infection elicits a robust long-lasting T-cell response, which makes CMV potentially promising vaccine vector against cancer. In the current study, we used recombinant murine (MCMV) strains as prophylactic therapeutic vaccines in an aggressive B16 lung metastatic melanoma model. Immunization MCMV-expressing ovalbumin (OVA) induced potent OVA-specific response was...
Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the vasculature (lymphangiogenesis). Diagnosis is typically made history, examination, radiology, and histologic findings. However, there significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases complex anomalies, all with PIK3CA variants but varying clinical...
BKM120, a pan class I PI3K inhibitor, was cytotoxic in the majority of primary B-chronic lymphocytic leukemia (CLL) lymphocytes, including samples from patients who have high-risk for poor response to treatment (patient with del11 and del17) at clinically obtainable concentrations. The PI3Kδ inhibitor Cal-101 is B-CLL lymphocytes vitro active CLL vivo. Interestingly, we demonstrated that BKM120 3.6 fold more toxic than malignant vitro. cytotoxicity correlated basal expression proteins...
Despite many years of research, cancer vaccines have largely been ineffective in the treatment established cancers. Many barriers to immune-mediated destruction malignant cells exist, and these likely limit efficacy vaccines. In this study, we sought enhance a Cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms immunotherapy. Adoptive cell therapy humans animal models shown be effective for tumor regression. Thus, assessed whether CMV-based...
Cancer vaccines that have utilized various immunization strategies to induce antitumor immunity largely failed in clinical settings. We recently developed a cancer vaccine using cytomegalovirus (CMV) based vector expressed modified melanoma antigen elicited robust CD8+ T cell response and tumor rejection.
Background: Ischemic stroke results in the activation of microglia, which may polarize toward a pro-inflammatory (M1) phenotype or an anti-inflammatory, neuroprotective (M2) phenotype. Thus, simultaneously suppressing M1 response and promoting M2 could be beneficial treatment stroke. Recently, epigenetic modulator Jmjd3 has been shown to essential for polarization. However, is antagonized by Ezh2 associated with we hypothesized that inhibition tilts balance between Ezh2, thereby enhancing...
Introduction: Inflammation plays an important role in exacerbating injury following stroke, but current understanding of the factors regulating this inflammation is incomplete. Pregnane X Receptor (PXR) a nuclear receptor which binds many xenobiotic targets including commonly prescribed medications. Recent work has shown that PXR crucial for maintaining integrity intestinal epithelial barrier as well repressing inflammatory responses mediated by NFκB. Since both these pathways can modify...
Abstract Methods for generating long-lived T cell responses to tumor antigen have been highly sought potential therapy against many cancers. Our group has recently developed a novel vaccine melanoma using recombinant Mouse Cytomegalovirus (MCMV) expressing modified which generated life-long CD8+ the antigen, gp100. While this delays growth in mouse model of B16 metastatic melanoma, mice eventually succumb disease. Adoptive shown clinical efficacy some patients with melanoma; however, it...
Background: It is now recognized that stroke a systemic stressor triggers profound changes throughout the body, leading to alterations in immune system and response. In CNS, cell death from ischemic activates glial cells, trafficking of leukocytes into brain subsequent inflammation. Chemokines play an active role modulating this recruitment process. Monocyte chemotactic protein-3 (MCP-3), also known as CCL7, chemokine attracts broad spectrum cells. Although secreted at lower levels than...
Abstract B-chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B-lymphocytes that are long-lived in-vivo but die quickly apoptosis when cultured in-vitro. The phosphatidylinositol-3 kinase (PI3K) cascade which a critical component survival signaling has increased activity in CLL lymphocytes as compared to normal B lymphocytes. There three classes PI3Ks class I most clearly implicated human cancer. PI3K-δ inhibitor, CAL-101, promotes and abrogated protection from...