Yihai Cao Group
General Research Description
Our research program focuses on studying the fundamental mechanisms of angiogenesis, the key process of blood vessel formation, in various diseases. Our aim is to understand molecular and functional mechanisms of angiogenesis in the onset and progression of most common and lethal human diseases such as cancer, metabolic disease, and cardiovascular disease. Through these mechanistic studies, we propose new concepts and paradigms that are beneficial for diagnosis, treatment, and prevention of these and other human diseases. The ultimate goal of our research is to develop novel therapeutics for treatment of angiogenesis-dependent diseases.
Cancer and Metastasis
In the cancer front, we are actively studying the mechanisms underlying invasion, metastasis, and drug responses. In particular, we study the interaction between tumor vessels and other cellular components in the tumor microenvironment for promoting cancer spreading and drug resistance. Our groundbreaking discoveries have provided new clues for effective treatment of various cancers by targeting the tumor vasculature. Our research project is translational in nature and clinically meaningful. We aim to improve the therapeutic efficacy of antiangiogenic drugs either alone or in combination with other therapeutic modalities. We have provided new mechanistic insights and rationales for antiangiogenic combination therapy with other therapeutics, improvement of antiangiogenic drug resistance, optimal timeline of therapy, mechanisms of action, and minimizing adverse effects (Figure 1). We have also discovered several novel mechanisms that underlie cancer metastasis. Recently, we have found that other cellular components including CAFs and TAMs mediate cancer metastasis through interacting with tumor vessels. In addition to blood stream metastasis, we have uncovered new mechanisms by which cancer cell spread through the lymphatic system. Lymphangiogenesis is an emerging interesting field and we are actively studying its role in cancer metastasis.
Obesisty and Metabolic Diseases
In the obesity and metabolic disease research front, we were one of the first in the world proposing the modulation of adipose vasculature for treating obesity, diabetes and other metabolic diseases. We have identified several novel molecular players that mediate the crosstalk between the vasculature and adipocytes. Using physiological cold exposure as an experimental tool, we have found that angiogenic vessels are crucial for controlling the metabolic status of adipocytes (Figure2 left: Vascular functions in adipose) Augmenting adipose angiogenesis can switch the white fat to become brown-like fat (browning fat). Moreover, we are able to make the most harmful visceral white fat to be metabolically beneficial browning fat, which helps to dissipate energy, leading to improvement of insulin sensitivity and metabolic dysfunctions in obese animals. We discovered novel mechanisms of vascular autocrine, paracrine and endocrine regulatory mechanisms for regulation of adipose tissue functions. Targeting angiogenesis has become a very exciting approach for treatment of obesity, diabetes, other metabolic diseases, their complications (Figure 3). We continue to work and lead this interesting research area. WE strongly believe that our findings will pave new avenues for developing novel therapeutics for treatment of obesity, diabetes and their complications.
Angiogenesis and other diseases
Our other research programs include therapeutic angiogenesis for treating cardiovascular disease, especially after myocardial infarction. We have developed a novel regimen of combination therapy targeting both angiogenesis and arteriogenesis. We have also developed novel therapeutics that target vasculatures, fibrosis, and inflammation for treating eye diseases including age-related macular disease (AMD) and glaucoma.. These novel therapeutics are ready for early clinical trials and preclinical studies demonstrated exciting therapeutic efficacy.
Targeting angiogenesis for the treatment of obesisty, diabetes and other metabolic diseases
In our research, we employ interdisciplinary experimental approaches to tackle clinically relevant unmet medical problems. We have created an exciting international environment for young scientists with different nationalities to work together. We welcome talented young scientists, postdoctoral fellows, Ph.D. students, and visiting scientists to join our team to work on these exciting research programs.
PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effects and drug resistance to Dll4-Notch inhibitors. Hideki Iwamoto, Yin Zhang, Takahiro Seki, Yunlong Yang, Masaki Nakamura, Jian Wang, Xiaojuan Yang, Takuji Torimura, Yihai Cao. Science Advances 10 Apr 2015: Vol. 1 no. 3 e1400244 DOI: 10.1126/sciadv.1400244
|Renhai Cao||Senior researcher|
|Li Chen||Biomedical scientist|
|Carina Fischer||PhD student, Graduate Student|
|Kayoko Hosaka||Senior lab manager|
|Takahiro Seki||Senior lab manager|
|Jieyu Wu||Graduate Student|