Aristidis Veves

Personal Information
Title Professor
Expertise Wound Healing
Institution Beth Israel Deaconess Medical
Data Summary
Grants/SubContracts 2
Progress Reports 0
Publications 0
Protocols 0
Committees 3
Experiments 0
Strains 0
Models 0


Clinical and Biochemical Biomarkers to Predict DFU Healing
Diabetic foot problems represent one of the major diabetes complications that significantly impair the quality of life of diabetic patients and lead to more than 750,000 new diabetic foot ulcers (DFU) and 70,000 lower extremity amputations per year in the USA alone. One of the major reasons that have impeded the development of new treatments is the lack of biomarkers that could act as surrogate endpoints in clinical trials and would allow the conduction of clinical trials that are of shorter duration and therefore, of considerably reduced cost. In addition, reliable biomarkers can be used in daily clinical applications to guide the selection of patients for new advanced, and also expensive, treatments and the frequency of application of such treatments. Our unit has a long tradition in conducting research to identify biomarkers related to the management of the diabetic lower extremity. Initial studies showed that changes in ulcer size over a 4-week period can predict very accurately the patients who are going to fail to heal their DFU. Subsequent studies investigated the predictive role of inflammatory cytokines and growth factors and showed that increased serum CRP, GM-CSF, IL-1a, sVCAM, VEGF, IL-17a, IFN?, Substance P, sICAM, IL-2, IL-8 and IL-23 are associated with failure to heal DFU. Finally, in collaboration with a startup company, we have shown that medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy- and deoxyhemoglobin can predict diabetic foot ulcer healing. The main aim of the current application is to further explore the development of imaging and biochemical markers that can predict DFU healing and can be used as surrogate endpoints in clinical trials. In addition, another important aim is to develop a local consortium that will include physicians and researchers from local teaching and community hospitals that will participate in the anticipated large clinical trial that will follow. The first aim will employ a newly designed handheld, battery operated, portable device (The HyperView, HyperMed Inc.) to develop algorithms that can predict DFU healing. The second aim will focus on developing multiplex assay panels which will measure previously identified cytokines and growth factors that are associated with DFU healing and develop prognostic algorithms. Finally, in the third aim we will compare the above techniques with the predictive value of changes in the DFU size over a 4-week period. By the end of the application, we will have developed the above two techniques to be ready for use for the main clinical trial. Questions that are expected to be addressed include their sensitivity and specificity, cost effectiveness, ease to use and acceptance by the practicing physicians. Furthermore, a consortium will be developed that will include physicians and researchers for teaching and community hospitals that will be ready to participate in the large clinical trial that will follow.

Single cell transcriptome sequencing of diabetic foot skin
Chronic wounds, including diabetic foot ulceration and venous ulcers, are a major problem that is associated with significant morbidity and mortality and financial cost. Recent studies by our unit and elsewhere have shown that chronic inflammation is one of the major factors that is associated with impaired wound healing2-4. Wound healing requires a well-coordinated action by numerous cell types, including neutrophils, monocyte/macrophages, fibroblasts, endothelial cells and keratinocytes. However, there is considerable lack of understanding of the molecular physiology of each of these cells that could lead to understanding of the pathophysiology of impaired wound healing. In this application, we propose to perform single-cell transcriptome sequencing from forearm and foot skin biopsies from healthy subjects and diabetic patients with foot ulcer. Our main will be to evaluate gene expression in various cell types and also explore possible differences in various body sites using highly robust drop-seq sequencing approach that allow evaluation of transcriptomic state of thousands of human cells in single experiment by measuring 4,000-7,000 genes. Finally, we will explore possible differences between diabetic and non-diabetic patients. Successful completion of this application will not only contribute to the development of a reference atlas of skin cells transcriptome state but can also play a major role in the development of new therapeutic approaches.

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