Calvin Kuo

Clinical Focus

• Cancer> Hematology
• Medical Oncology

Honors and Awards

• Research Chair, NIH Intestinal Stem Cell Consortium, NIH (2009)
• Transformative R01 Award, NIH (2009)
• 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)

Professional Education

Postdoctoral Advisees

Wai Man Chan,  Junlei Chang,  Junlei Chang,  David Corney,  Valda Hilliard,  Valda Hilliard,  Cynthia Kosinski,  Lincoln Nadauld,  James Neal,  James Neal,  Stephanie Piecewicz,  Mario Vallon,  Mario Vallon,  Kelley Yan

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Immunology
• Medicine
• Chemical and Systems Biology
• Cardiovascular Medicine

Internet Links

• Kuo Lab website

Current 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 methods towards these goals.

Publications

• PDGF-B exploits stromal EPO. McGinnis LM, Kuo CJ. Nat Med. 2012; 18 (1): 22-4
• The HIF Signaling Pathway in Osteoblasts Directly Modulates Erythropoiesis through the Production of EPO. Rankin EB, Wu C, Khatri R, Wilson TL, Andersen R, Araldi E, Rankin AL, Yuan J, Kuo CJ, Schipani E, Giaccia AJ. Cell. 2012; 149 (1): 63-74
• The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Yan KS, Chia LA, Li X, Ootani A, Su J, Lee JY, Su N, Luo Y, Heilshorn SC, Amieva MR, Sangiorgi E, Capecchi MR, Kuo CJ. Proc Natl Acad Sci U S A. 2012; 109 (2): 466-71
• Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling. Shkreli M, Sarin KY, Pech MF, Papeta N, Chang W, Brockman SA, Cheung P, Lee E, Kuhnert F, Olson JL, Kuo CJ, Gharavi AG, D'Agati VD, Artandi SE. Nat Med. 2011; 18 (1): 111-9
• Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Kuhnert F, Mancuso MR, Shamloo A, Wang HT, Choksi V, Florek M, Su H, Fruttiger M, Young WL, Heilshorn SC, Kuo CJ. Science. 2010; 330 (6006): 985-9