Ge Ruowen Lab

Research Interests:

1. Tumor angiogenesis, antiangiogenic proteins, anticancer drugs:

Angiogenesis (new blood vessel formation) is essential for embryonic development and adult physiological functions such as wound healing, reproduction, and tissue homeostasis. Abnormal angiogenesis is involved in more than 70 human diseases including cancer. To suppress cancer through inhibiting tumor angiogenesis has been actively pursued as an anticancer therapeutic approach.

In recent years, we have focused on identifying and investigating novel endogenous anti-angiogenesis proteins that contain the thrombospondin type 1 repeat domain (TSR). These endogenous proteins are not only valuable for anticancer drug development but also important for understanding tissue homeostasis and organ function. So far, we have identified 3 novel endogenous antiangiogenic proteins: Isthmin 1 (ISM1), ADAMTS5, and ADAMTS4. We use CRISPR/Cas9 gene-editing approach to generate knockout mice for functional investigations. We also study the mechanisms of action of these proteins using cultured primary human endothelial cells and various molecular and cell biology approaches. Notably, we discovered a previously unrecognized protein trafficking pathway from late endosome to mitochondria which allows extracellular antiangiogenic proteins to reach mitochondria via endocytosis and execute apoptosis. We believe this is a fundamental protein trafficking pathway that is likely to exist in many cell types. We are currently investigating what are the key players in this protein trafficking pathway and how late endosomes interact and fuse with mitochondria.

2. Inflammation suppression and resolution, COPD, lung homeostasis:

We are also interested in inflammation suppression and resolution. We have discovered a novel endogenous protein inflammation suppressor that can quench cigarette-smoke-induced Chronic Obstructive Pulmonary Disease (COPD) and help to maintain lung homeostasis in mice. COPD is the 3rd leading cause of human mortality and morbidity globally with a huge social-economic burden (after cardiovascular disease and cancer). We are currently investigating the mechanism of action of this novel protein in lung homeostasis, COPD, and other inflammatory lung diseases such as acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF).

3. Peptide drug discovery and development for cancer and COPD:

We are also interested in developing peptide-based drugs for cancer and inflammation. Using multiple approaches, several proapoptotic peptide agonists have been developed targeting cell-surface GRP78. These peptides are being further developed into theranostics (therapeutics + diagnostics) for cancer and COPD.