A5059492810- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Pancreatic and Hepatic Oncology Research
- Immune Cell Function and Interaction
- Galectins and Cancer Biology
- RNA Interference and Gene Delivery
- Angiogenesis and VEGF in Cancer
- Cancer Mechanisms and Therapy
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Drug Transport and Resistance Mechanisms
- Melanoma and MAPK Pathways
- Signaling Pathways in Disease
- Polyomavirus and related diseases
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Colorectal and Anal Carcinomas
- Plant Virus Research Studies
- FOXO transcription factor regulation
- Esophageal Cancer Research and Treatment
- Bacteriophages and microbial interactions
- Toxin Mechanisms and Immunotoxins
- Renal and related cancers
Harvard University
2012-2024
Brigham and Women's Hospital
2012-2024
Boston Children's Hospital
2010-2024
Men's Health Boston
2018
Harvard Stem Cell Institute
2017
University of Würzburg
2008-2011
VA Boston Healthcare System
2010-2011
Dana-Farber Cancer Institute
2010
Woman's Hospital
2009
Massachusetts General Hospital
2008
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...
Self‐renewing cancer stem cells (CSC) capable of spawning more differentiated tumor cell progeny are required for tumorigenesis and neoplastic progression leukemias several solid cancers. The mechanisms by which CSC cause initiation growth currently unknown. Recent findings that suggest a negative correlation between degrees host immunocompetence rates development raise the possibility only restricted minority malignant cells, namely CSC, may possess phenotypic functional characteristics to...
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...
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...
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Inhibitors targeting the programmed death 1 (PD-1) immune checkpoint have improved MCC patient outcomes by boosting antitumor T immunity. Here, we identify PD-1 as growth-promoting receptor intrinsic to cells. In human lines clinical tumors, RT-PCR–based sequencing, immunoblotting, flow cytometry, immunofluorescence analyses demonstrated gene protein expression MCC–PD-1 ligation enhanced, its inhibition or silencing...
Understanding the mechanisms that regulate nephron progenitors during kidney development should aid of therapies for renal failure. MicroRNAs, which modulate gene expression through post-transcriptional repression specific target mRNAs, contribute to differentiation stem cells, but their role in nephrogenesis is incompletely understood. Here, we found loss miRNAs results a premature depletion this population development. Increased apoptosis and pro-apoptotic protein Bim accompanied...
Impaired regulatory B cell (Breg) responses are associated with several autoimmune diseases in humans; however, the role of Bregs type 1 diabetes (T1D) remains unclear. We hypothesized that naturally occurring, interleukin-10 (IL-10)–producing maintain tolerance to islet autoantigens, and hyperglycemic nonobese diabetic (NOD) mice T1D patients lack these potent negative regulators. IgVH transcriptome analysis revealed islet-infiltrating cells long-term normoglycemic (Lnglc) NOD, which...
Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cell-intrinsic functional regulation not well understood. Here, we demonstrate induction of in melanoma cells via type I interferon (IFNAR) signaling reversal ICB efficacy through IFNAR pathway inhibition. Treatment with...
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...
Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While development these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce toxicity are still needed. We hypothesized that delivery anti–PD-1 antibody encapsulated PLGA nanoparticles (anti–PD-1 NPs) spleen would antitumor effect this agent. Unexpectedly, we found mice treated with a high dose NPs exhibited significantly higher...