M.D., Ph.D., Professor
Laboratory of Targeted Cancer Therapy
Research Interests or Current Research Focus
1. The group has demonstrated that legumain combined with integrin activates both pro-cathepsin L and pro-MMP2, of which over-expression in tumors promotes tumor invasion and metastasis. Focus in a subset of cell surface anchoring or associated proteases that are over-expressed in most human cancers, such as legumain. Targeting legumain protease was aimed at tumor-targeting small molecules and prodrugs development.
2. Study tumor-Associated Macrophages (TAMs), which promotes the malignant tumor metastasis. The mechanism and effect of TAMs are unclear. Legumain is highly expressed in TAM, while it is absent or expressed at comparatively low level in normal tissues. Legumain may be involved in TAM’s metastasis promotion.
3. Osteoclast plays an important role in tumor bone metastasis. Legumain may interact with TRAF6, one of the signal molecules involved in the major differentiation axis of osteoclast, that is, RANKL\RANK\TRAF6 signal pathway. Legumain knockout and overexpression mice will be applied to testify its function in differentiation and bone absorption function of osteoclast.
4. Research genes related with immune function of macrophages and dendritic cells, which exert influence on tumor growth and metastasis. KO mice would be an ideal model for syngenic tumor transplantation, in order to characterize these immune genes. Gelatin-9 KO(Lgals9), Mcl KO(Clec4d), Pomgnt1 KO(Pomgnt1) and DC-SIGN KO(Cd209a) mice will be applied.
Major Research Achievement
1. Selective chemotherapy using catalytic aldolase antibody 38C2 redirected to cell-surface receptors using integrin-targeting
compounds (Publication: PNAS, 2006).
2. Aldolase antibody 38C2 as a catalyst for the prodrug activation (Publication: PNAS, 2007).
1982-1987: M.D., School of Clinical Medicine, Fujian Medical University, China
1992-1998: Ph.D., Pathology, Department of Pathology, Nippon Medical School, Tokyo, Japan
Major Academic Appointments
2000-2004: Postgraduate Researcher Scientist, Dept. of Medicine, UCI, Irvine & Cancer Center, UCSD, CA, USA
2004-2008: Staff Scientist, the Scripps Research Institute, La Jolla, CA, USA
2008-present: Professor/PI, Institute of Health Sciences, Shanghai, China
- Guo F, Liu Y, Wu W, Kuo P, Liu C. Selective ablation of Tumor-Associated Macrophage suppresses Metastasis and Angiogenesis. Submitted.
- Liu Y*, Guo F*, Wu W, Kuo P, Shumilak K, Liu C. Hypoxia- induced legumain expression and localization to invasive cell surface via co-factor αvβ3 integrin is critical for tumor invasion and angiogenesis. (*, equal contribution). Submitted.
- Abraham S*, Guo F*, Li LS, Rader C, Liu C, Barbas III CF, Lerner RA, Sinha SC. Synthesis of the next Generation therapeutic antibodies that combine cell targeting and antibody catalyzed. Proc Natl Acad Sci USA, 104 (13):5584-5589 (2007). (*, equal contribution).
- Guo F, Das S, Mueller BM, Barbas III CF, Lerner RA, Sinha SC. Breaking the one antibody-one target axiom. Proc Natl Acad Sci USA, 2006;103 (29):11009-11014.
- Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumato Y, Lander AD, Korc M. Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin binding growth factors in breast cancer cells. Cancer Res, 2001;61: 5562-5569.
- Guo F*, Ishiwata T, Yokoyama M, Asano G. Expression of basic fibroblast growth factor, epidermal growth factor, and their receptors in castrated and testosterone injected rat prostates. Acta Histochemica ET Cytochemica, 1997;30: 13-22. (*, correspondent).
- Guo F*, Qiao Y, Wei L, kameyama K, Ishiwata T, Naito Z, Asano G. Morphometrical evaluation of effects of androgen on castrated rat prostate, with special reference to morphological changes of epithelial cells, stromal cells and blood vessels. Japanese Journal of Clinical Electron Microscopy, 1997;30: 41-49. (*, correspondent).
- Minev BR, Guo F, Gueorguieva I, Kaiser HE. Vaccines for immunotherapy of breast and prostate cancer: new developments and comparative aspects. In Vivo, 2002;16:405-416.
- Wei L, Guo F, Kudo M, Asano G. Epithelial and stromal changes after castration and testosterone treatment in rat prostate. Connective Tissue, 30: 17-25 (2000).
- Nishigaki R, Guo F, Onda M, Yamada N, Yokoyama M, Naito Z, Asano G, Shimizu-Suganuma M, Shichinohe K, Aramaki T. Ultrastructural changes and immunohistochemical localization of nitric oxide synthase, advanced glycation end products and NF-B in aorta of streptozotocin treated Mongolian gerbils. Journal of Nippon Medical School, 66: 166-175 (1999).
- Dang C, Takashi E, Guo F, Naito Z, Yokoyama M, Asano G, Ji Z, Qin Z. Ultrastructural study of the mechanism of perineural extension in pancreatic cancer. Medical Electron Microscopy, 31: 31-37 (1998).
- Ishiwata T, Guo F, Naito Z, Asano G. Differential distribution of ecNOS and iNOS mRNA in rat heart after endotoxin administration. Japanese Heart Journal, 38: 445-455 (1997).
- Nishigaki R, Guo F, Yokoyama M, Naito Z, Asano G. Ultrastructural changes and localization of nitric oxide synthase in rat lung induced by endotoxin administration. Medical Electron Microscopy, 30: 177-184 (1997).
- Fukui M, Qiao Y, Guo F, Asano G. Cell damage and liberation of nitric oxide syntheses in rat heart induced by endotoxin administration. Journal of Nippon Medical School, 62: 469-481 (1995).