A5022291678- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Corneal Surgery and Treatments
- RNA Interference and Gene Delivery
- Drug Transport and Resistance Mechanisms
- Cancer Immunotherapy and Biomarkers
- Mesenchymal stem cell research
- Corneal surgery and disorders
- Ocular Surface and Contact Lens
- Wound Healing and Treatments
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Angiogenesis and VEGF in Cancer
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Skin and Cellular Biology Research
- Ocular Oncology and Treatments
- Cell Adhesion Molecules Research
- Melanoma and MAPK Pathways
- Colorectal and Anal Carcinomas
- Retinal Development and Disorders
- Connective tissue disorders research
- Tissue Engineering and Regenerative Medicine
- Ocular Disorders and Treatments
- Immune Cell Function and Interaction
VA Boston Healthcare System
2016-2025
Brigham and Women's Hospital
2016-2025
Harvard University
2015-2024
Harvard Stem Cell Institute
2018-2024
Boston Children's Hospital
2015-2024
Smith-Kettlewell Eye Research Institute
2023
Massachusetts Eye and Ear Infirmary
2023
Edith Cowan University
2023
Broad Institute
2018
Boston Children's Museum
2016
Abstract Enhanced drug efflux mediated by ABCB1 P-glycoprotein and related ATP-binding cassette transporters is one of several mechanisms multidrug resistance thought to impair chemotherapeutic success in human cancers. In malignant melanoma, its potential contribution chemoresistance uncertain. Here, we show that ABCB5, which functions as a determinant membrane regulator cell fusion physiologic skin progenitor cells, expressed clinical melanoma tumors preferentially marks subset...
Abstract Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence antitumor immunity. Thus, only a restricted minority tumorigenic cells may possess phenotypic and functional characteristics needed to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis. Tumorigenic ABCB5+ initiating (MMICs) possessed capacity preferentially inhibit IL-2–dependent T-cell activation support, in B7.2-dependent...
Significance The mechanical integrity of the arterial wall is dependent on a properly structured ECM. Elastin and collagen are key structural components ECM, contributing to stability elasticity normal arteries. Lysyl oxidase (LOX) normally cross-links elastin molecules in process forming proper fibers elastic lamellae. Here, using whole-genome sequencing humans genome engineering mice, we show that missense mutation LOX causes aortic aneurysm dissection because insufficient cross-linking...
Cell fusion involving progenitor cells is a newly recognized phenomenon thought to contribute tissue differentiation. The molecular mechanisms governing cell are unknown. P-glycoprotein and related ATP-binding cassette transporters expressed by cells, but their physiological role in these types has not been defined. Here, we have cloned ABCB5, rhodamine efflux transporter novel member of the human family, which marks CD133-expressing among epidermal melanocytes determines as regulator...
Melanoma growth is driven by malignant melanoma-initiating cells (MMIC) identified expression of the ATP-binding cassette (ABC) member ABCB5. ABCB5(+) melanoma subpopulations have been shown to overexpress vasculogenic differentiation markers CD144 (VE-cadherin) and TIE1 are associated with CD31(-) mimicry (VM), an established biomarker increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in MMIC-dependent VM tumor growth. Global gene analyses, validated mRNA...
Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and regeneration. Though of prime interest, their potentially protective role on neutrophil-induced damage, associated with high morbidity mortality, has not been explored in sufficient detail. Here we report the therapeutic skill MSCs to suppress unrestrained neutrophil activation attenuate severe damage a murine immune-complex mediated vasculitis model unbalanced activation. MSC-mediated suppression was due intercellular...
Abstract Identification and reversal of treatment resistance mechanisms clinically refractory tumor cells is critical for successful cancer therapy. Here we show that ATP-binding cassette member B5 (ABCB5) identifies therapy-refractory in colorectal patients following fluorouracil (5-FU)–based chemoradiation therapy provide evidence a functional role ABCB5 5-FU resistance. Examination human colon specimens revealed to be expressed only on rare within healthy intestinal tissue, whereas...
The drug efflux transporter ABCB5 identifies cancer stem-like cells (CSC) in diverse human malignancies, where its expression is associated with clinical disease progression and tumor recurrence. confers therapeutic resistance, but other functions tumorigenesis independent of have not been described that might help explain why it so broadly overexpressed cancer. Here we show melanoma-initiating cells, controls IL1β secretion, which serves to maintain slow cycling, chemoresistant through an...
Abstract Caveolin (CAV) 1 and 2 are integral membrane proteins that constitute major components of small pouches termed caveolae. While several functions have been described in other tissues, the roles CAV1 CAV2 ocular surface remained unknown. In current study, we investigated expression function human cornea. We found to be preferentially expressed by proliferative Basal Cell Adhesion Molecule (BCAM)-positive progenitor cells along entire limbal corneal basal epithelial layer. Functional...
Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, mechanisms behind this effect are poorly understood. We previously demonstrated that deficiency of is associated with decreased tumor macrophage accumulation a model sporadic intestinal tumorigenesis. In study, we aimed to determine role stromal expression murine syngeneic transplantable cancer model. show host growth CCR6-expressing cancers. Colon cancers...
In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing ATP-binding cassette subfamily B member 5 (ABCB5) for therapy nonhealing wounds. Local administration ABCB5
Abstract Background While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly standard treatment. GMP-manufactured skin-derived ABCB5 + mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing engraftment potential, ability adaptively inflammatory signals, healing-promoting efficacy in mouse models human chronic venous...
Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, paucity markers for isolation molecularly defined immunomodulatory cell populations poses barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable exerting therapeutic functions through engagement programmed death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T proliferation, evaded immune rejection, homed...
Background aimsHuman dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell–based therapy of various currently uncurable diseases in several fields regenerative medicine. We have developed and validated method to isolate, from human skin samples, expand ABCB5+ MSCs that meet the guideline criteria International Society Cellular Therapy. are able process these into Good Manufacturing Practice–conforming, MSC-based advanced-therapy...
BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and life-threatening inherited skin fragility disorder that comes about due to lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, tissue-healing capacities. In Col7a1-/- mouse model RDEB, treatment with MSCs markedly extended the animals' lifespans.METHODSIn this international,...