Li, Yan

Abstract BACKGROUND Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. OBJECTIVE To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy. METHODS Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions. EXPECTED OUTCOMES With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine. DISCUSSION The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.

Heart transplantation is a surgical procedure performed on patients with end-stage heart failure or other irreversible heart disease, Heart transplant prolongs the life of severe heart disease patients. Most of the receipts could survive more than 2-3 years, five-year survival rate could reach 70-80% with immunosuppressive therapy, rejection still an important problem after transplantation. Currently, traditional calcineurin inhibitors, antimetabolite agents, and steroids, wildly used after transplantation, the new generation of immunosuppressive medicines have been developed, and cell-based immunotherapy, as mesenchymal stem cell, myeloid-derived suppressor cells, dendritic cells, pluripotent cells and Treg cells are promising to be used in cellular immunotherapy in organ transplantation.