The Laboratory of Lawrence L.K. Leung, MD

The Leung Lab Research

1.      Thrombin-Activatable Carboxypeptidase B2 (CPB2) in the Crosstalk between Coagulation, Thrombosis, Inflammation and Innate Immunity

Procarboxypeptidase B2 circulates as an inactive enzyme and is activated by the thrombin/thrombomodulin complex on endothelial cell surface. Activated CPB2 inactivates a variety of inflammatory mediators including C3a, C5a, bradykinin, and thrombin-cleaved osteopontin. Thus CPB2, along with activated protein C, represents a physiological homeostatic mechanism to regulate thrombin’s inflammatory activity. We use the pro-CPB2 deficient mouse to define CPB’s role in various thrombotic and inflammatory disease models.

2.      Thrombin Cleavage of Osteopontin in Cancer Biology

Thrombin cleavage of osteopontin (OPN), a matricellular protein, exposes a novel integrin-binding site at its newly exposed C-terminus. Thrombin-cleaved OPN (OPN-Arg) is elevated in various inflammatory diseases, and CPB2, by removing the C-terminal arginine, inhibits the inflammatory activity of OPN-Arg. Using a thrombin-non-cleavable OPN knock-in mouse, we are studying the role of thrombin cleavage of OPN in cancer biology.

3.      Chemerin and Insulin Resistance

Chemerin is an adipokine and chemoattractant. Its activation and subsequent inhibition is regulated by successive proteolytic cleavages at its C-terminus, involving serine proteases (including clotting factor XIa) and carboxypeptidases (including CPB2). We are studying the role of chemerin in insulin resistance using the prochemerin deficient  mouse in obesity models as well as clinical samples from patients undergoing bariatric surgery.

4.      Epidemiology Center in Research and Information (ERIC) in support of genomics at Palo Alto VA

The Palo Alto ERIC is dedicated to the translation of the Million Veteran Program (MVP) which is one of the world’s largest genomic databases.

Location & Contact Info

The Leung Lab is located at the Palo Alto VA, 3801 Miranda Ave.
Lab phone: 650-493-5000, ext 68414

Most recent publications:

  1. Ge X, Yamaguchi Y, Zhao L, Bury L, Greasele P, Berube C, Leung LL, Morser J. Prochemerin cleavage by factor XIa links coagulation and inflammation. Blood 2018, 131:353-364. (Commentary: Meijers JCM. Blood 131:275-276).
  2. Morser J, Shao Z, Nishimura T, Zhou Q, Zhao L, Higgins J, Leung LLK. Carboxypeptidase B2 and N play different roles in regulation of activated complements C3a and C5a in mice. J. Thromb. Haemost. 2018, 16:991-1002. (Commentary: Foley JH, Conway EM. JTH 16:987-990).
  3. Zhao L, Yamaguchi Y, Ge X, Robinson W, Morser J, Leung L. Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients. Art Res Ther2018, 20:132-141. PMID: 29973268
  4. Zhao L, Yamaguchi Y, Shen WJ, Morser J, Leung LLK. Dynamic and tissue-specific processing of chemerin in obese mice. PLOS One2018, In press.
  5. Li J, Pan C, Zhang S, Spin J, Deng A, Leung LLK, Dalman RL, Tsao PS, Snyder M. Decoding the genomics of abdominal aortic aneurysm. Cell 2018, In press. 
  6. Leung LLK, Morser J. Carboxypeptidase B2 and carboxypeptidase N in the crosstalk between coagulation, thrombosis, inflammation, and innate immunity. J. Thromb. Haemost. 2018; [Epub ahead of print] PMID: 29883024