A5060755857- Systemic Sclerosis and Related Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune cells in cancer
- Connective Tissue Growth Factor Research
- Inflammatory Myopathies and Dermatomyositis
- Inhalation and Respiratory Drug Delivery
- Nanoplatforms for cancer theranostics
- Skin and Cellular Biology Research
- Skin Diseases and Diabetes
- Epigenetics and DNA Methylation
- Dermatologic Treatments and Research
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Autoimmune Bullous Skin Diseases
- Transplantation: Methods and Outcomes
- Pancreatic function and diabetes
- Pediatric health and respiratory diseases
- Ferroptosis and cancer prognosis
- Salivary Gland Disorders and Functions
- Mesenchymal stem cell research
- HER2/EGFR in Cancer Research
- Eosinophilic Disorders and Syndromes
- Chemokine receptors and signaling
- Signaling Pathways in Disease
University College London
2014-2024
MacroGenics (United States)
2018-2024
Aptose Biosciences (United States)
2024
Thermo Fisher Scientific (United States)
2023
The Royal Free Hospital
2014-2021
University of Pennsylvania
2004
Pfizer (United States)
2002
Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this is co-opted into contributing toward tumor growth instead preventing its progression. We seek to reestablish an antitumor by selectively targeting surface receptors and endogenous signaling processes macrophage subtypes driving cancer RP-182 synthetic 10-mer amphipathic analog host defense peptides that induces conformational switch mannose receptor CD206...
Rationally sequencing and combining PD-1/L1-and MAPK-targeted therapies may overcome innate acquired resistance. Since increased clinical benefit of MAPK inhibitors (MAPKi) is associated with previous immune checkpoint therapy, we compare the efficacies sequential and/or combinatorial regimens in subcutaneous murine models melanoma driven by BrafV600, Nras, or Nf1 mutations as well colorectal pancreatic carcinoma KrasG12C. Anti-PD-1/L1 lead-in preceding MAPKi combination optimizes response...
Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects targeting CD206 receptor M2-like with a novel synthetic analogue naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds on bone marrow-derived (BMDM) vitro, resulting time-dependent expression and transient increase M1-macrophage marker TNF-α....
The effects of high-fat feeding on the development obesity were evaluated in intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice fed a diet for < or =50 days. Serum tissues collected at baseline after 1, 11, 50 days diet. After 11 diet, ICAM-1-deficient, but not B6, developed fatty livers showed significant increase inguinal fat pad weight. At day 50, ICAM-1-deficient weighed less, their adiposity index circulating leptin levels significantly lower than those B6...
Background/Objectives: The identification of inflammatory mediators and the involvement CD206 macrophages in anti-inflammatory responses, along with synthesis fibrotic mediators, are crucial for diagnosis treatment Idiopathic Pulmonary Fibrosis (IPF). Methods: In this study, assessment 68Ga-labeled linear cyclic forms RP832c peptide, which demonstrate a specific affinity macrophages, was performed to evaluate efficacy imaging through PET/CT, biodistribution studies, staining...
Cytokines released by infiltrating T cells may promote mechanisms leading to fibrosis in scleroderma. The aim of this study was investigate the role Th2 cytokine IL-31, and its receptor IL-31RA, scleroderma skin lung fibrosis.IL-31 measured ELISA plasma, immunochemistry fibrotic tissue patients. receptor, assayed qPCR resident cells. Next-generation sequencing used profile responses normal fibroblasts IL-31. In wild-type Balb/c mice, IL-31 administered subcutaneous mini pump, with or without...
In systemic sclerosis (SSc), a persistent tissue repair process leads to progressive fibrosis of the skin and internal organs. The role mesenchymal stem cells (MSCs), which characteristically initiate regulate repair, has not been fully evaluated. We undertook this study investigate whether dividing metakaryotic MSCs are present in SSc examine exposure disease microenvironment activates transdifferentiation.Skin biopsy material from patients with recent-onset diffuse was examined by...
Activated M2 polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios such as Acute Respiratory Disease Syndrome (ARDS) and Idiopathic Pulmonary Fibrosis (IPF), through the production inflammatory fibrosis-inducing cytokines. In this study, we investigated effect targeting CD206 receptor with a novel fragment Host Defense Peptide (HDP), RP-832c to decrease cytokines that cause fibrosis. selectively binds on bone marrow derived (BMDM) vitro , resulting...
Tumor-associated macrophages (TAMs) are large phagocytic cells that play numerous roles in cancer biology and an important component of the relationship between immune system response tumor progression. The peptide, RP832c, targets Mannose Receptor (CD206) expressed on M2-like is cross-reactive to both human murine CD206. Additionally, it exhibits therapeutic properties through its ability shift population TAMs from (protumor) toward M1-like phenotype (antitumor) has demonstrated promise...
Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc order identify enhancing factors, measure effect of migrating cells on underlying extracellular matrix (ECM) test possible therapeutic inhibitors. Novel patterned collagen substrates were used investigate alignment lung fibroblasts from patients healthy controls. Normal but not consistently elongated aligned with migrated dependent PDGF or...
Abstract Background/Aims In health IgG immunoglobulins form a network through interaction with cell surface proteins and controlled by regulatory cells, whereas in autoimmune diseases responses become skewed towards higher affinity potentially damaging against self-antigens. Moreover, recent studies have demonstrated activation of the epithelial layer skin systemic sclerosis (SSc), implicating keratinocytes as target process. We investigated presence plasma autoantibodies directed sought...
Abstract Background/Aims Calcinosis may result from localised trans-differentiation of tissue resident stem cells in the subcutaneous layer affected skin systemic sclerosis (SSc), as a severe disabling manifestation linked to ischaemia and local trauma. Polarised macrophages synergistically promote osteogenesis: M1 recruit mesenchymal leading osteogenic differentiation, while M2 are responsible for osteoblast formation. Previous studies have implicated two pathways-Activin-A signalling CD206...
<h3>Background:</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by the production of autoantibodies, which leads to fibrosis and finally damage various tissues organs. Recent studies have demonstrated activation aberrant persistence M2-like macrophages in tissues, implicating these cells as a source pro-fibrotic inflammatory mediators. However, interplay between autoantibodies remains largely unexplored. In this study, we aimed investigate role disease-specific...
Abstract Background/Aims Systemic sclerosis (SSc) is a rare and progressive connective tissue disease that more common in women the third to fifth decades of life children. Calcinosis cutis, deposition calcium deposits within subcutaneous tissue, remains challenging non-lethal complication SSc. The development calcinosis cutis poorly understood area there are no functional mouse models or laboratory for In this study we present clinical database analysis plus two potential vitro examining...
pattern in 4 (36.4%).Extra-nuclear antibodies (ENA) were positive 5 patients, mainly anti-Scl70 (36.4%).Sarcoidosis was biopsy proven one had a Kveim test and considered to have sarcoidosis based on clinical features supportive investigations.Five patients single-organ involvement related (lung, lacrimal gland, lymph nodes).Interstitial lung disease (ILD) present (45.5%), majority of these harboured antibodies.60% radiological changes attributable both diseases the remaining 2 SSc or...
prescribed HPN, which is life-saving in patients with severe bowel involvement. Our study shows that HPN offers a safe means of nutritional support for SSc-related GI involvement, but mortality remains high. The catheter-related sepsis rate SSc was low. In addition, the majority relied on others their catheter care. Disclosure statement: authors have declared no conflicts interest.
<h3>Background</h3> Stabilised caprine corticotrophin releasing hormone is long acting neuropeptide that targets its cognate receptor in the skin and hypothalamus. <h3>Objectives</h3> The aim of this study was to examine role stabilized-release hormone-1 (SR-CCRH-1) an extract from hyperimmune sera (HICS) could act as anti-fibrotic agent murine bleomycin (BLM)-induced pulmonary fibrosis model. <h3>Methods</h3> Two parallel studies were used; one functional other pathology-based, using...
<h3>Background</h3> Stabilized-release caprine corticotrophin releasing hormone-1 (SR-CCRH-1) is held in a multi-protein complex and derived from hyperimmune sera (HICS). SR-CCRH-1 may have an efficacy trait accordingly warranted investigation. <h3>Objectives</h3> The objective of the study was to determine whether novel stabilized-release neuropeptide could elicit measurable as anti-fibrotic agent murine bleomycin (BLM)-induced skin fibrosis model (an vivo used demonstrate therapeutic...
Background: Using a broad screening methodology, c-Kit was identified as an induced phosphoprotein in migrating lung fibroblasts.Minority stem cell populations expressing have been demonstrated tissue, capable of regenerating epithelial and endothelial cells after injury.We went on to study the subpopulation using factor (SCF) growth ligand investigate SCF/c-kit potential driving fibrotic process SSc possible therapeutic target.Methods: Aligned collagen matrices designed model fibroblast...
Abstract Multiple lines of evidence suggest that macrophages, in particular M2-polarized tumor associated macrophages (TAMs), promote aggressiveness and chemoresistance. Thus, limiting the pro-tumorigenic activity TAMs may hold great therapeutic promise. To assess this potential, we synthesized artificial peptides (10-12mers) with a striapathic arrangement hydrophobic hydrophilic amino acids, designed to specifically target within microenvironment. These peptides, including drug candidate...