Calvin Kuo

Calvin Kuo, MD, PhD, Maureen Lyles D'Ambrogio Professor of Medicine and Hematology, Stanford University School of Medicine 

Research Description: My laboratory has several interests related to diabetes. In particular, we have had an active interest in organoid culture of the pancreas and of pancreatic cancer using an airliquid interface in which not only epithelial cells are maintained but are grown in continuity which stromal cells including mesenchymal and immune components without reconstitution. We have used these organoid systems over the years to also engineer oncogenic mutations to achieve malignant transformation of wild-type pancreatic organoids to adenocarcinoma as well as to model the pancreatic cancer tumor immune microenvironment (Nat. Med. 2014, Cell 2018) (1,2). In other work, we have also published several papers in which we have found that FDAapproved VEGF inhibitors such as aflibercept improve glucose tolerance and can treat animal models of diabetes, by stimulating cross-talk between the hypoxia and insulin signaling pathways, with sensitization of hepatic insulin signaling (Wei et al., Nature Med 2013a; Taniguchi et al., Nat. Med., 2013b) (3,4).

Selected relevant publications (Stanford DRC members in BOLD):

  1. Li X, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, Cantrell MA, Rack PG, Neal JT, Chan CW, Yeung T, Gong X, Yuan J, Wilhelmy J, Robine S, Attardi LD, Plevritis SK, Hung KE, Chen CZ, Ji HP, Kuo CJ. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nature Medicine. (2014) Jul;20(7):769-77. doi: 10.1038/nm.3585. Epub 2014 May 25. PMID: 24859528

  2. Neal JT, Li X, Zhu J, Giangarra V, Liu IH, Chiou SH, Salahudeen AA, Smith AR, Deutsch BC, Ju J, Liao L, Zemek AJ, Zhao F, Karlsson K, … Sunwoo JB, Sabatti S, Boehm JS, Hahn WC, Zheng GXY, Davis MM, Kuo CJ. Organoid modeling of the tumor immune microenvironment. Cell (2018) Dec 13;175(7):1972-1988.e16. doi: 10.1016/j.cell.2018.11.021. PMID: 30550791

  3. Wei K, Piecewicz SM, McGinnis LM, Taniguchi CM, Wiegand SJ, Anderson K, Chan CW, Mulligan KX, Kuo D, Yuan J, Vallon M, Morton LC, Lefai E, Simon MC, Maher JJ, Mithieux G, Rajas F, Annes JP, McGuinness OP, Thurston G, Giaccia AJ, Kuo CJ. A liver Hif-2α-Irs2 pathway sensitizes hepatic insulin signaling and is modulated by Vegf inhibition. Nature Medicine Oct;19(10):1331-7 (2013). doi: 10.1038/nm.3295. PMID: 24037094

  4. Taniguchi CM, Finger EC, Krieg AJ, Wu C, Diep AN, Lagory EL, Wei K, McGinnis LM, Yuan J, Kuo CJ, Giaccia AJ. Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes. Nature Medicine. Oct;19(10):1325-30 (2013). doi: 10.1038/nm.3294. PMID: 24037093