- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Cannabis and Cannabinoid Research
- Cardiovascular Health and Disease Prevention
- Diabetes Management and Education
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cardiovascular Function and Risk Factors
- Pancreatic and Hepatic Oncology Research
- Organ Donation and Transplantation
- Diet and metabolism studies
- HIV-related health complications and treatments
- Pancreatitis Pathology and Treatment
- Immune Cell Function and Interaction
- Chronic Disease Management Strategies
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Transplantation: Methods and Outcomes
- Cardiovascular Disease and Adiposity
- Angiogenesis and VEGF in Cancer
Leiden University Medical Center
2016-2025
Royal Netherlands Academy of Arts and Sciences
2013-2025
Hubrecht Institute for Developmental Biology and Stem Cell Research
2014-2025
Leiden University
2011-2024
Netherlands School of Public Administration
2022-2024
Gelre Hospitals
2022
University Medical Center Utrecht
2011-2021
Utrecht University
1998-2019
Cancer Genomics Centre
2016-2019
KU Leuven
2018
To understand organ function, it is important to have an inventory of its cell types and their corresponding marker genes. This a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies typically done on pooled islets Langerhans, obscuring contributions from rare potential subpopulations. overcome this challenge, we developed automated platform that uses FACS, robotics, CEL-Seq2 protocol obtain transcriptomes...
Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional diabetes. The number obtained from type diabetic patients culture was 44% lower compared age- sex-matched control subjects (P < 0.001). This reduction inversely related to levels HbA(1c) (R...
Adult mitotic tissues like the intestine, skin, and blood undergo constant turnover throughout life of an organism. Knowing identity stem cell is crucial to understanding tissue homeostasis its aberrations upon disease. Here we present a computational method for derivation lineage tree from single-cell transcriptome data. By exploiting topology composition, establish StemID, algorithm identifying cells among all detectable types within population. We demonstrate that StemID recovers two...
Abdominal obesity is a well-established risk factor for the development of type 2 diabetes. However, sex differences may exist. We aimed to investigate associations abdominal subcutaneous adipose tissue (SAT) and visceral (VAT) with insulin resistance secretion in men women.In this cross-sectional analysis Netherlands Epidemiology Obesity study, fasting postprandial concentrations glucose were measured fat depots assessed using magnetic resonance imaging 2253 participants (53% women). With...
Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control people with type 1 2 diabetes.We performed short-term observational cohort study at Leiden University Medical Center. People ≥18 years were eligible participate. Participants filled out online questionnaires, sent...
Atherosclerosis is a low-grade inflammatory disease involving leukocytes, lipids, and glucose leading to endothelial dysfunction. Since activation of neutrophils by triglycerides has been described in vitro, we hypothesized that the postprandial phase an state affecting possibly contributing We measured blood leukocyte counts, cytokines, hydroperoxides (HPOs), flow-mediated vasodilation (FMD) eight healthy males (age 23 ± 2 years) after FAT (50 g/m2) GLUCOSE challenge (37.5 g/m2),...
An abdominal imaging window allows in vivo visualization of dynamic cellular processes, including liver metastasis and islet cell transplantation.
Abstract Purpose: Hypertension is a commonly reported side effect in antiangiogenic therapy. We investigated the hypothesis that telatinib, small molecule angiogenesis inhibitor, impairs vascular function, induces rarefaction, and causes hypertension. Experimental Design: A side-study was done phase I trial of tyrosine kinase inhibitor endothelial growth factor receptors 2 3, platelet-derived receptor, c-KIT patients with advanced solid tumors. Measurements blood pressure, flow-mediated...
In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein patients with type 1 diabetes, enabling restoration normoglycemia.After intra-hepatic transplantation several factors involved in decay mass and function mainly caused by an immediate blood mediated inflammatory response, lack vascularization, allo-and autoimmunity.Bioengineered scaffolds can potentially provide alternative extra-hepatic site for improving nutrient diffusion supply to...
Loss of pancreatic islet β-cell mass and dysfunction are central in the development type 2 diabetes (T2DM). We recently showed that mature human insulin-containing β-cells can convert into glucagon-containing α-cells ex vivo. This loss identity was characterized by presence transcription factors (Nkx6.1, Pdx1) glucagon+ cells. Here, we investigated whether also occurs vivo, it is related to (pre)diabetes humans nonhuman primates. observed an eight times increased frequency insulin+ cells...
Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing number. Here we present novel in vitro platform generate functional from three-dimensional cultures mouse human intestinal crypts. We show that short-chain fatty acids selectively increase the number cells, resulting an elevation This is accompanied by upregulation...
High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance insulin resistance. However, the long-term effects pancreatic endocrine cells unknown. In this study we investigate tolerance β- α-cell mass mice. Despite an initial loss, did not result after 22 wk. Plasma markers associated with dyslipidemia...
Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe 3D culture system that supports the expansion adult pancreatic tissue and generation subpopulation with progenitor characteristics. These display high aldehyde dehydrogenase activity (ALDHhi), express progenitors markers (PDX1, PTF1A, CPA1, MYC), can form new organoids in contrast ALDHlo cells. Interestingly, gene expression profiling...