A5087966663- Immune cells in cancer
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- S100 Proteins and Annexins
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Angiogenesis and VEGF in Cancer
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Extracellular vesicles in disease
- Chemokine receptors and signaling
- Psoriasis: Treatment and Pathogenesis
- Adenosine and Purinergic Signaling
- Skin and Cellular Biology Research
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Complement system in diseases
- Bioactive Compounds and Antitumor Agents
- Electrospun Nanofibers in Biomedical Applications
- Atherosclerosis and Cardiovascular Diseases
- Proteoglycans and glycosaminoglycans research
- Wnt/β-catenin signaling in development and cancer
Lemuel Shattuck Hospital
2019-2024
Duke University
2019-2020
Georgetown University Medical Center
2012-2017
Georgetown University
2012-2017
Vince Lombardi Cancer Clinic
2016
University of Virginia
2008-2009
The HER2-specific monoclonal antibody (mAb), trastuzumab, has been the mainstay of therapy for HER2+ breast cancer (BC) approximately 20 years. However, its therapeutic mechanism action (MOA) remains unclear, with antitumor responses to trastuzumab remaining heterogeneous and metastatic BC incurable. Consequently, understanding MOA could enable rational strategies enhance efficacy. Using both murine human versions we found activity dependent on Fcγ receptor stimulation tumor-associated...
Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) targeted antibodies. Preclinically, CD47/SIRPα blockade induces antitumor activity increasing tumor cells macrophages and enhancing cross-presentation antigens CD8+ T dendritic cells; both these processes are potentiated CD40 signaling. Here we generated novel, two-sided fusion protein incorporating extracellular...
Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and enabled the development personalized vaccines oncology. Establishing feasibility delivering complex multispecific modalities that require higher-order structures important their function could help expand use mRNA/LNP biologic formulations. Here, we evaluated whether administration formulations SIRPα-Fc-CD40L TIGIT-Fc-LIGHT achieve oligomerization extend...
Abstract IL26 is a unique amphipathic member of the IL10 family cytokines that participates in inflammatory signaling through canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular signaling. Although has almost no described role cancer, our vivo screen cytokine pathway genes revealed be one most significant mediators mammary engraftment lung metastatic growth triple-negative breast cancer (TNBC). Examination human cancers demonstrated...
Abstract Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) PD-1/PD-L1 (PD-1/L1) may improve response rates compared monotherapy PD-1/L1 blockade in checkpoint naive non–small lung cancer PD-L1 expression >50%. mAbs an effector-competent Fc can induce myeloid activation, some have demonstrated effector T depletion, which carries a clinical liability unknown significance. Ab translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), be...
Bone marrow-derived cells (BMCs) and inflammatory chemokine receptors regulate arteriogenesis angiogenesis. Here, we tested whether arteriolar remodeling in response to an stimulus is dependent on BMC-specific (C-C motif) receptor 2 (CCR2) expression this involves BMC transdifferentiation into smooth muscle.Dorsal skinfold window chambers were implanted C57Bl/6 wild-type (WT) mice, as well the following bone marrow chimeras (donor-host): WT-WT, CCR2(-/-)-WT, WT-CCR2(-/-), EGFP(+)-WT. One day...
Abstract Poly( D,L ‐lactic‐ co ‐glycolic acid) (PLGA) is a biodegradable polymer that widely used for drug delivery. However, the degradation of PLGA alters local microenvironment and may influence tissue structure and/or function. Here, we studied whether affects arteriolar microcirculation through arteriogenic expansion maximum lumenal diameters formation new smooth muscle‐coated vessels. Single microspheres comprised 50:50 (521 ± 52.7 μm diameter), with bovine serum albumin (BSA) (547...
<div>Abstract<p>Lipid nanoparticle (LNP)–encapsulated mRNA has been used for <i>in vivo</i> production of several secreted protein classes, such as IgG, and enabled the development personalized vaccines in oncology. Establishing feasibility delivering complex multispecific modalities that require higher-order structures important their function could help expand use mRNA/LNP biologic formulations. Here, we evaluated whether administration formulations SIRPα-Fc-CD40L...
<p>Supplemental Figure 1</p>
<p>Supplemental Figure 1</p>
<div>Abstract<p>Lipid nanoparticle (LNP)–encapsulated mRNA has been used for <i>in vivo</i> production of several secreted protein classes, such as IgG, and enabled the development personalized vaccines in oncology. Establishing feasibility delivering complex multispecific modalities that require higher-order structures important their function could help expand use mRNA/LNP biologic formulations. Here, we evaluated whether administration formulations SIRPα-Fc-CD40L...
<h3>Background</h3> Previously, we characterized the bispecific Fc fusion protein (TIGIT-Fc-LIGHT) that blocks PVR checkpoint axis and agonizes TNFRs through LIGHT. In a preclinical tumor model of acquired resistance to PD-1 blockade (CT26/AR), exposure TIGIT-Fc-LIGHT promoted antitumor activity, suggesting immune costimulation mediated by LIGHT may broaden clinical utility TIGIT blockade. can promote vascular remodeling LTbR/HVEM linking targeting peptide (VTP) is one strategy enrich...
Abstract Fibroblast growth factors (FGFs) play a crucial role during embryonic development, tissue homeostasis, wound healing and angiogenesis. FGF-binding protein 1 (FGFBP1) is secreted that binds FGFs stored in the extracellular matrix transports them to their receptor, therefore they can modulate FGF signaling. FGFBP1 contributes progression of many cancers including colon, pancreas squamous cell cancer. It acts as an angiogenic switch tumor development. E0771 cells, murine mammary...
Abstract The complex cross-talk occurring among cells in the tumor microenvironment influences anti-cancer immune response. Here we employed an RNAi screen of a murine cancer cell line syngeneic to C57Bl/6 mice parse out ability system identify and eliminate malignant cells. To rate-limiting modulators, EO771 mammary was transduced with barcoded genome-wide shRNA library engrafted immune-competent as well immune-deficient mice. Analysis tumors grown presence functional adaptive compared...
Abstract Cancer cell vascular invasion is a crucial step in the malignant progression towards metastasis. Here we used genome-wide RNAi screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as candidate. Krtap5-5 belongs large family cysteine-rich proteins that implicated crosslinking keratin intermediate filaments during hair formation. To date, no role these has been reported. found depletion...
Abstract Metastatic spread of cancer cells from their primary site requires invasion into the vasculature, evasion at distant organ and colonization organ. Here we studied mechanisms attachment endothelial monolayers by to identify driver molecules signaling pathways that are crucial for invasive metastatic phenotype. Different human mouse cell lines were transduced with lentiviral-based, genome-wide or kinome-targeted shRNA libraries. Cancer populations different phenotype then selected...
<div>Abstract<p>IL26 is a unique amphipathic member of the IL10 family cytokines that participates in inflammatory signaling through canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular signaling. Although IL26 has almost no described role cancer, our <i>in vivo</i> screen cytokine pathway genes revealed be one most significant mediators mammary engraftment lung metastatic growth triple-negative breast cancer...