Blood vessels undergo rapid functional and structural changes, known as angiogenesis and vascular remodeling, in numerous malignant conditions. The significance of these vascular changes has been highlighted in earlier genetic and molecular studies, particularly in relation to pathological conditions such as cancer. However, challenges remain: 1) devising effective strategies to delay metastatic progression by targeting the tumor vasculature within the tumor microenvironment, and 2) elucidating the potential interactions between the vascular changes and the immune system in disease progression.

Our current investigations encompass several interconnected topics:

  1. Understanding the molecular mechanisms by which vascular abnormalities facilitate tumor immune suppression, such as T cell exclusion, and resistance to immunotherapy in primary and metastatic tumors.
  2. Elucidating the mechanisms underlying resistance to anti-VEGF therapy in liver metastases of pancreatic neuroendocrine tumors.
  3. Identifying the potential of circulating vascular factors as effective predictive or prognostic biomarkers in cancer patients.
  4. Determining the vascular contributions to the progression of Alzheimer’s disease, focusing on identifying mechanisms that compromise the blood-brain barrier.

We employ an integrated approach that combines preclinical studies using genetically engineered mouse models with translational studies involving human biospecimens. The goal of our study is to pave the way for the development of novel and more effective therapeutic strategies targeting abnormal blood vessels, with the aim of preventing or delaying disease progression.