Calvin Kuo

Clinical Focus

• Cancer > Hematology
• Medical Oncology

Honors and Awards

• Member, American Society for Clinical Investigation, American Society for Clinical Investigation (2007)
• Samantha Janower Research Chair, Brain Tumor Society (2005)
• Merck Faculty Development Award, Merck (2003)
• Kimmel Foundation Scholar in Translational Science, Kimmel Foundation (2002)
• Burroughs Wellcome Foundation New Investigator in Pharmacological Sciences, Burroughs Wellcome Foundation (2001)

Professional Education

Postdoctoral Advisees

Xingnan Li

Web Site Links

• Kuo Lab website

Industry Relationships

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Research Interests

Angiogenesis.
We are interested in determining functions of novel molecules regulating angiogenesis including receptors such as GPCRs, microRNAs and secreted molecules. Typically, we use loss-of-function approaches through knockout and conditional knockout mice. We also have extensive experience using adenoviral expression of soluble receptor ectodomains to inhibit angiogenic pathways including VEGF and PDGFRb. Loss-of-function phenotypes would simulate the effects of pharmacologic inhibition of novel targets for anti-angiogenic therapy of cancer and ocular disorders.

Endothelial cell regulation of physiology,
How do endothelial cells regulate physiology of their host organs? The liver hepatocyte appears particularly responsive to its host endothelial cells. We are investigating effects of VEGF inhibition on hepatocyte functions in terms of Epo synthesis, erythropoiesis and metabolic pathways. We are also correlating these changes with anti-tumor response and survival in cancer patients receiving VEGF inhibitors, as potential surrogate biomarkers of efficacy.

Intestinal stem/progenitor biology.
The complete regeneration of the epithelial lining of the intestine every 5-7 days renders the intestine a model system for studying stem cell behaviors. We are investigating the regulation of the intestinal stem cell (ISC) compartment by extracellular signals such as Wnts, using adenoviral and conditional knockout approaches. Further, we have derived robust methods for prolonged culture of and ex vivo expansion of primary intestinal tissue, with preservation of ISCs. Additional methods are under development for purification and analysis of mouse and human ISCs.

Nanoparticle-mediated systemic siRNA delivery.
The potential of siRNA to silence currently undruggable targets such as intracellular transcription factors is tempered by substantial obstacles to systemic siRNA delivery. We are working collaboratively to use nanoparticle-based...

Publications

• Endochondral ossification is required for haematopoietic stem-cell niche formation. Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT, Wei K, Helms JA, Kuo CJ, Kraft DL, Weissman IL. Nature. 2009; 457 (7228): 490-4
• Increased hemoglobin associated with VEGF inhibitors in advanced renal cell carcinoma. Harshman LC, Kuo CJ, Wong BY, Vogelzang NJ, Srinivas S. Cancer Invest. 2009; 27 (8): 851-6
• Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, Kuo CJ. Nat Med. 2009; 15 (6): 701-6
• Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ, Kuo CJ. Development. 2008; 135 (24): 3989-93
• Recombinant adenovirus as a methodology for exploration of physiologic functions of growth factor pathways. Wei K, Kuhnert F, Kuo CJ. J Mol Med. 2008; 86 (2): 161-9