A5041150382- Acute Myeloid Leukemia Research
- Angiogenesis and VEGF in Cancer
- Cancer Cells and Metastasis
- Hematopoietic Stem Cell Transplantation
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Metastasis and carcinoma case studies
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Developmental Biology and Gene Regulation
- Wound Healing and Treatments
- Immune responses and vaccinations
- Single-cell and spatial transcriptomics
- Immune Response and Inflammation
- MicroRNA in disease regulation
- Chronic Myeloid Leukemia Treatments
- FOXO transcription factor regulation
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
University Hospital of Zurich
2019-2024
University of Zurich
2020-2024
University of Lisbon
2016-2019
Instituto Gulbenkian de Ciência
2007-2013
Juntendo University
2013
Instituto Português de Oncologia Francisco Gentil
2007-2012
Universidade Nova de Lisboa
2010-2012
IPO Porto
2011-2012
Instituto Português de Oncologia de Coimbra Francisco Gentil
2007-2010
Clonal hematopoiesis of indeterminate potential (CHIP), also referred to as aging-related clonal hematopoiesis, is defined an asymptomatic expansion mutant mature hematopoietic cells in ≥4% blood leukocytes. CHIP associates with advanced age and increased risk for hematological malignancy, cardiovascular disease, all-cause mortality. Loss-of-function somatic mutations TET2 are frequent drivers CHIP. However, the contribution aging-associated cooperating cell-extrinsic drivers, like...
In the last decade there have been multiple studies concerning contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute adults is termed postnatal vasculogenesis occurs via four inter-related steps. They must respond chemoattractant signals mobilize from bone marrow peripheral blood; home on sites formation; invade migrate at same sites; differentiate into mature (ECs) and/or...
Aging is associated with impaired hematopoietic and immune function caused in part by decreased fitness the stem cell (HSC) population an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. Here we demonstrate that older specific pathogen free (SPF) wild-type (WT) mice contrast to young SPF produce more interleukin-1a interleukin-1b (IL-1a/b) steady-state bone marrow (BM), most of IL-1a/b being derived from BM cells....
Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1+ T cells, which associate with improved long-term survival stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion differentiation "Delta One T" (DOT) we found DOT cells be highly cytotoxic against AML primary samples lines,...
Genome editing often takes the form of either error-prone sequence disruption by non-homologous end joining (NHEJ) or replacement homology-directed repair (HDR). Although NHEJ is generally effective, HDR difficult in primary cells. Here, we use a combination immunophenotyping, next-generation sequencing, and single-cell RNA sequencing to investigate reprogram genome outcomes subpopulations adult hematopoietic stem progenitor We find that although quiescent stem-enriched cells mostly NHEJ,...
<title>Abstract</title> Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those harvested from a donor, and is received by 40,000 patients worldwide each year. To quantify dynamics of long-term engraftment, we sequenced whole genomes 2,824 single-cell-derived colonies samples 10 donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT. With younger donors, 10,000–50,000 had engrafted were still contributing to...
Abstract Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those from a donor 1,2 . Here, to quantify dynamics of long-term engraftment, we sequenced genomes 2,824 single-cell-derived colonies ten donor–recipient pairs taken 9–31 years after HLA-matched sibling HCT 3 With younger donors (18–47 at transplant), 5,000–30,000 had engrafted and were still contributing haematopoiesis time sampling; estimates tenfold lower older...
Abstract Metabolic reprogramming is central to tumorigenesis, but whether chemotherapy induces metabolic features promoting recurrence remains unknown. We established a mouse xenograft model of human acute myeloid leukemia (AML) that enabled chemotherapy-induced regressions disease followed by lethal regrowth more aggressive tumor cells. Human AML cells from terminally ill mice treated with (chemoAML) had higher lipid content, increased lactate production and ATP levels, reduced expression...
Bone marrow (BM) derived vascular precursor cells (BM-PC, endothelial progenitors) are involved in normal and malignant angiogenesis, ischemia wound healing. However, the mechanisms by which BM-PC stimulate pre-existing at sites of remodelling/recovery, their contribution towards formation new blood vessels still undisclosed. In present report, we exploited possibility that members Notch signalling pathway, expressed during differentiation, might regulate pro-angiogenic or pro-wound healing...
Abstract Chemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. Here, we develop an experimental model system using vitro lineage tracing coupled with exome, transcriptome vivo functional readouts to assess AML population dynamics associated molecular determinants underpinning chemoresistance...
Recent findings have shown that the blood vessels of different organs exert an active role in regulating organ function. In detail, endothelium aligns vasculature most is fundamental maintaining homeostasis and promoting recovery following injury. Mechanistically, endothelial cells (EC) tissues such as liver, lungs or bone marrow (BM) been to produce "angiocrine" factors promote restore normal Controlled production angiocrine injury therefore essential regeneration However, molecular...
Timely detection of colorectal cancer metastases may permit improvements in their clinical management. Here, we investigated a putative role for bone marrow-derived cells the induction epithelial-to-mesenchymal transition (EMT) as marker onset metastasis. In ectopic and orthotopic mouse models cancer, CD11b(Itgam)(+)Jagged2 (Jag2)(+) infiltrated primary tumors surrounded tumor that exhibited diminished expression E-cadherin increased vimentin, 2 hallmarks EMT. vitro coculture experiments...
Neo-blood vessel growth (angiogenesis), which may involve the activation of pre-existing endothelial cells (EC) and/or recruitment bone marrow-derived vascular precursor (BM-VPC), is essential for tumor growth. Molecularly, besides well established roles Vascular factor (VEGF), recent findings show Notch signalling pathway, in particular ligand Delta-like 4 (Dll4), also adequate angiogenesis; Dll4 inhibition results impaired, non-functional, angiogenesis and reduced However, role BM-VPC...
Delta-like 4 (Dll4) is a ligand of the Notch pathway family which has been widely studied in context tumor angiogenesis, its blockade shown to result non-productive angiogenesis and halted growth. As Dll4 inhibitors enter clinic, there an emerging need understand their side effects, namely systemic consequences Dll4:Notch tissues other than tumors. The present study focused on effects anti-Dll4 targeting bone marrow (BM) microenvironment. Here we show that with monoclonal antibodies perturbs...