- Pancreatic function and diabetes
- Mesenchymal stem cell research
- Diabetes and associated disorders
- Diabetes Management and Research
- Tissue Engineering and Regenerative Medicine
- Wound Healing and Treatments
- Electrospun Nanofibers in Biomedical Applications
- Pancreatic and Hepatic Oncology Research
- Diabetes Treatment and Management
- Virus-based gene therapy research
- Hematopoietic Stem Cell Transplantation
- Cancer Cells and Metastasis
- Airway Management and Intubation Techniques
- COVID-19 diagnosis using AI
- 3D Printing in Biomedical Research
- Renal Transplantation Outcomes and Treatments
- Biomedical Ethics and Regulation
- Periodontal Regeneration and Treatments
- Glycosylation and Glycoproteins Research
- X-ray Diffraction in Crystallography
- Gastrointestinal disorders and treatments
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Organ and Tissue Transplantation Research
- Cardiac Fibrosis and Remodeling
South Tees Hospitals NHS Foundation Trust
2025
Western University
2016-2024
Vanderbilt University
2018-2023
University of California, San Diego
2021
Geisinger Medical Center
2019
Nashville Oncology Associates
2018-2019
Humboldt-Universität zu Berlin
2014-2016
University of Freiburg
2014-2016
John Wiley & Sons (Germany)
2014-2016
Crystal Research (United States)
2014-2016
Posttransplantation diabetes mellitus (PTDM) is a common and significant complication related to immunosuppressive agents required prevent organ or cell transplant rejection. To elucidate the effects of 2 commonly used agents, calcineurin inhibitor tacrolimus (TAC) mTOR sirolimus (SIR), on islet function test whether these could be reversed prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC SIR at clinically relevant levels. Both impaired insulin...
Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and pancreas over a range of ages states diabetes. Very few LDs were found normal juvenile pancreatic acinar cells, numbers subsequently increasing throughout adulthood. While appeared evenly distributed postjuvenile cells donors without diabetes, enriched α-...
Pancreatic islets secrete insulin from β cells and glucagon α cells, dysregulated secretion of these hormones is a central component diabetes. Thus, an improved understanding the pathways governing coordinated cell hormone will provide insight into islet dysfunction in However, 3D multicellular architecture, essential for function, presents experimental challenges mechanistic studies intracellular signaling primary cells. Here, we developed integrated approach to study function human using...
Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells, changes their expression are associated with developmental state diabetes. However, the implications of heterogeneity TF across islet cell populations not well understood. To define this its consequences for function, we profiled more than 40,000 cells from normal human islets by single-cell RNA-Seq stratified based on combinatorial expression. Subpopulations coexpressing...
Abstract Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles tumor delivery has been largely empirical, owing to a lack quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants into blood vessel determined. It is shown that dependent surface charge. Moreover, size dependency strongly suggests taken up by...
Impaired skin wounds represent a significant and growing complication associated with type II diabetes effective clinical strategies to reproducibly induce wound resolution do not exist. As class of secreted nonstructural matrix proteins that modulate many cellular aspects healing, matricellular could novel mechanism promote healing. Based on their role in the regulation proliferative phase we hypothesized local delivery periostin CCN2 suppress inflammation progress into remodeling phases...
Decellularized adipose tissue (DAT) scaffolds represent a promising cell-instructive platform for soft engineering. While recent work has highlighted that mesenchymal stromal cells, including adipose-derived cells (ASCs), can be combined with decellularized to augment regeneration, the mechanisms involved require further study. The objective of this was probe roles syngeneic donor ASCs and host-derived macrophages in remodeling DAT within an immunocompetent mouse model. Dual transgenic...
Background: There is a need to identify and quantify mesenchymal stromal cells (MSCs) in human bone marrow aspirate concentrate (BMAC) source tissues, but current methods do so were established cultured cell populations. Given that surface marker gene expression change cells, it doubtful these strategies are valid MSCs fresh BMAC. Purpose: To establish the presence, quantity, heterogeneity of BMAC-derived minimally manipulated BMAC using currently available strategies. Study Design:...
Background: The zebrafish genetic mutant iguana ( igu ) has defects in the ciliary basal body protein Dzip1, causing improper cilia formation. Dzip1 also interacts with downstream transcriptional activators of Hedgehog (Hh), Gli proteins, and Hh signaling is disrupted mutants. governs a wide range developmental processes, including stabilizing developing blood vessels to prevent hemorrhage. Using embryos treated pathway antagonist cyclopamine, we conducted microarray determine genes involved...
Cell-based therapies involving the delivery of adipose-derived stromal cells (ASCs) on decellularized adipose tissue (DAT) scaffolds are a promising approach for soft augmentation and reconstruction. Our lab has recently shown that culturing human ASCs DAT within perfusion bioreactor prior to implantation can enhance their capacity stimulate in vivo regeneration. Building from this previous work, current study investigated effects preconditioning ASC phenotype secretory profile vitro , as...
Accessory molecule interactions can be critical in determining the outcome of a T cell's encounter with antigen. Cell adhesion proteins may augment cell responses by facilitating TCR engagement antigen-MHC complex, while co-stimulatory molecules deliver distinct signals that modulate responsiveness. CD43 (leukosialin, sialophorin) has been suggested to influence activation steric hindrance based upon large size and glycosylation protein, as well relative abundance protein on surface. In this...
Cytolytic T lymphocytes (CTL) were able to specifically bind and lyse allogeneic P815 tumor cells LPS blast in suspension. An assay was developed measure the rate of target cell binding suspension independent lysis. Target found plateau within 3 hr The presence free, functional CTL targets at these plateaus demonstrated, indicating that an equilibrium process. Scatchard plots used derive values for Kd (apparent affinity) bmax (maximum binding). could not be blocked by purified plasma...
Abstract Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment type 2 diabetes and act primarily to lower blood by preventing reabsorption in kidney. However, it is controversial whether these agents also on pancreatic islet, specifically α cell, increase glucagon secretion. To determine effects SGLT2 human islets, we analyzed expression hormone secretion islets treated with inhibitor dapagliflozin (DAPA) vitro vivo. Compared kidney, SLC5A2...
The past decade has witnessed the increased use of patient simulation in medical training as a method to teach complex bedside skills. Although effective bag-mask ventilation (BMV) is critical part airway management, quality this skill been questioned.First-year internal medicine house staff (novices) were used evaluate computerized simulator tool difficult BMV. A novice group and an expert (certified registered nurse anesthetists anesthesiologists) tested validate simulator's ability...
SUMMARY A hallmark of type 2 diabetes (T2D), a major cause world-wide morbidity and mortality, is dysfunction insulin-producing pancreatic islet β cells 1–3 . T2D genome-wide association studies (GWAS) have identified hundreds signals, mostly in the non-coding genome overlapping cell regulatory elements, but translating these into biological mechanisms has been challenging 4–6 To identify early disease-driving events, we performed single spatial proteomics, sorted transcriptomics, assessed...