Yihai Cao Group

We research in Angiogenesis, Cancer, Metabolic disease, Cardiovascular disease and Eye disease.

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.

Yihai Cao

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.


We focus our efforts on studying alterations of the tumor microenvironment in affecting tumor growth, metastasis, and drug responses. We are particularly interested in studying the vascular functions in promoting tumor growth and metastasis and in understanding the mechanisms underlying antiangiogenic therapy. Our research mechanistic projects include:

  1. Fundamental mechanisms of tumor angiogenesis
  2. Studying the role of tumor vessels in supporting primary tumor growth
  3. Tumor vessels and cancer metastasis
  4. Lymphangiogensis and lymphatic metastasis
  5. Interactions between tumor stromal cellular and molecular components
  6. Tumor microenvironment in cancer metastasis
  7. Antiangiogenic drug resistance
  8. Cancer metabolism and anticancer drug response
  9. Translational research towards clinical therapy
  10. Defining novel therapeutic targets and development of more effective therapies

Obesity and Metabolic Diseases

We are interested in investigating the mechanisms and functions of the adipose vasculature in regulating adipose metabolism. We are beginning to understand the crucial roles of the adipose vasculature in modulating adipocyte functions under metabolic quiescent and active states. Targeting the adipose vasculature provides a new concept and paradigm for treating obesity, metabolic disease such as type 2 diabetes mellitus, and metabolic disease complications. Our research projects and interests include the following aspects:

  1. Angiogenesis in obesity and metabolic disease
  2. Vascular stem cells in contributing to adipose tissue development and functions
  3. Interactions between vascular cells and adipocytes
  4. Non-shivering thermogenesis in energy expenditure
  5. Growth factors, adipocytokines, adipokines in mediating the vasculature-adipocyte dialog
  6. Brown adipose tissue and browning white adipose tissues activation and metabolic disease
  7. Vascular functions in development of liver steatosis and NASH
  8. Endocrine functions of adipose tissues
  9. Vascular roles in development of diabetic complications
  10. Defining novel therapeutic targets for treatment of obesity and T2DM

Other projects

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.

Snapshot of scientific publications

Total published articles 241

21 articles in Nature publishing group (2 Nature; 3 Nature Medicine; 1 Nature Reviews Cancer; 1 Nature Reviews Clinical Oncology; 1 Nature Reviews Drug Discovery; 2 Nature Reviews Endocrinology; 7 Nature Communications; 5 Natural Protocols)

14 articles in Cell press group (1 Cell; 2 Cancer Cell; 5 Cell Metabolism; 3 Cell Reports; 1 Developmental Cell, 1 Neuron)    

7 articles in Science and sister journals (2 Science; 2 Science Translational Medicine; 2 Science Advances; 1 Science Signaling)

60 articles published in other top journals: 45 articles in Proc Natl Acad Sci U S A; 10 articles in J. Clin. Invest (8 JCI, 2 JCI Insight); 4 articles in Circulation; 4 articles in J. Exp. Med, 4 articles in Blood.

Selected publications:

Selected 10 original research articles

Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance.
Iwamoto H, Abe M, Yang Y, Cui D, Seki T, Nakamura M, et al
Cell Metab. 2018 Jul;28(1):104-117.e5

Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay.
Martinez Molina D, Jafari R, Ignatushchenko M, Seki T, Larsson EA, Dan C, et al
Science 2013 Jul;341(6141):84-7

Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis.
Dong M, Yang X, Lim S, Cao Z, Honek J, Lu H, et al
Cell Metab. 2013 Jul;18(1):118-29

PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells.
Xue Y, Lim S, Yang Y, Wang Z, Jensen LD, Hedlund EM, et al
Nat. Med. 2011 Dec;18(1):100-10

Hypoxia-independent angiogenesis in adipose tissues during cold acclimation.
Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, et al
Cell Metab. 2009 Jan;9(1):99-109

PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.
Cao R, Björndahl MA, Religa P, Clasper S, Garvin S, Galter D, et al
Cancer Cell 2004 Oct;6(4):333-45

Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2.
Cao R, Bråkenhielm E, Pawliuk R, Wariaro D, Post MJ, Wahlberg E, et al
Nat. Med. 2003 May;9(5):604-13

Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PlGF-1/VEGF heterodimers.
Eriksson A, Cao R, Pawliuk R, Berg SM, Tsang M, Zhou D, et al
Cancer Cell 2002 Feb;1(1):99-108

Angiogenesis inhibited by drinking tea.
Cao Y, Cao R
Nature 1999 Apr;398(6726):381

Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function.
Cheng H, Cao Y, Olson L
Science 1996 Jul;273(5274):510-3

Selected 10 review articles

Adipocyte and lipid metabolism in cancer drug resistance.
Cao Y
J. Clin. Invest. 2019 07;129(8):3006-3017

Obesity Protects Cancer from Drugs Targeting Blood Vessels.
Cao Y
Cell Metab. 2018 06;27(6):1163-1165

VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs.
Cao Y
Nat Rev Endocrinol 2014 Sep;10(9):530-9

Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity.
Cao Y
Cell Metab. 2013 Oct;18(4):478-89

Forty-year journey of angiogenesis translational research.
Cao Y, Arbiser J, D'Amato RJ, D'Amore PA, Ingber DE, Kerbel R, et al
Sci Transl Med 2011 Dec;3(114):114rv3

Optimizing the delivery of cancer drugs that block angiogenesis.
Cao Y, Langer R
Sci Transl Med 2010 Jan;2(15):15ps3

Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases.
Cao Y
Nat Rev Drug Discov 2010 Feb;9(2):107-15

Off-tumor target--beneficial site for antiangiogenic cancer therapy?
Cao Y
Nat Rev Clin Oncol 2010 10;7(10):604-8

Positive and negative modulation of angiogenesis by VEGFR1 ligands.
Cao Y
Sci Signal 2009 Feb;2(59):re1

Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis.
Cao Y
Nat. Rev. Cancer 2005 09;5(9):735-43

Publications 2019-2020

Regorafenib induces lethal autophagy arrest by stabilizing PSAT1 in glioblastoma.
Jiang J, Zhang L, Chen H, Lei Y, Zhang T, Wang Y, et al
Autophagy 2020 Jan;16(1):106-122

CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance.
Langebäck A, Bacanu S, Laursen H, Mout L, Seki T, Erkens-Schulze S, et al
Sci Rep 2019 Dec;9(1):19384

Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.
Ge C, Huang H, Huang F, Yang T, Zhang T, Wu H, et al
Proc. Natl. Acad. Sci. U.S.A. 2019 Sep;116(39):19635-19645

Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy.
Uribesalgo I, Hoffmann D, Zhang Y, Kavirayani A, Lazovic J, Berta J, et al
EMBO Mol Med 2019 08;11(8):e9266

Endothelial life discontinues without Erk.
Cao Y
J. Exp. Med. 2019 Aug;216(8):1730-1732

Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization.
Ali Z, Mukwaya A, Biesemeier A, Ntzouni M, Ramsköld D, Giatrellis S, et al
Arterioscler. Thromb. Vasc. Biol. 2019 Jul;39(7):1402-1418

Adipocyte and lipid metabolism in cancer drug resistance.
Cao Y
J. Clin. Invest. 2019 07;129(8):3006-3017

Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis.
Sui W, Li H, Yang Y, Jing X, Xue F, Cheng J, et al
Proc. Natl. Acad. Sci. U.S.A. 2019 May;116(22):10937-10942

Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris.
Ali Z, Cui D, Yang Y, Tracey-White D, Vazquez-Rodriguez G, Moosajee M, et al
Dev. Biol. 2019 Feb;():

All Publications

Yihai Cao Publications on PubMed

Group Members