Selected Articles
Künzli BM, Nuhn P, Enjyoji K, Banz Y, Smith RN, Csizmadia E, Schuppan D, Berberat PO, Friess H, Robson SC. Disordered pancreatic inflammatory responses and inhibition of fibrosis in CD39-null mice. Gastroenterology. 2008 Jan;134(1):292-305. Epub 2007 Oct 25.
* Enjyoji K, Kotani K, Thukral C, Blumel B, Sun X, Wu Y, Imai M, Friedman D, Csizmadia E, Bleibel W, Kahn BB and Robson SC. Deletion of Cd39/Entpd1 results in hepatic insulin resistance. Diabetes in press.
* Beldi G, Wu Y, Imai M, Enjyoji K, Csizmadia E, Candinas D, Erb L, Robson SC. Regulated catalysis of extracellular nucleotides by vascular CD39/ENTPD1 is required for liver regeneration. Gastroenterology in press.
* Beldi G, Wu Y, Banz Y, Nowak M, Miller L, Enjyoji K, Yegutkin GG, Candinas D, Exley M and Robson SC. NTK cell dysfunction in CD39/Entpd1 null mice protects against Concanavalin A-induced hepatitis. Hepatology in press.
* Jackson SW, Hoshi T, Wu Y, Sun X, Enjyoji K, Cszimadia E, Sundberg C, Robson SC. Disordered purinergic signaling inhibits pathological angiogenesis in Cd39/Entpd1-null mice. Am J Pathol 2007 Oct;171(4):1395-404. Epub 2007 Sep 6. Prior work in Circulation. 2001; 104: 3109-3115 clearly demonstrated that CD39 is required for co-ordinated endothelial cell, macrophage and pericyte migration patterns; deletion of Cd39 blocked angiogenesis within matrigel plugs. More recently, this work has been extended to show defective angiogenesis within implanted tumors and in the setting of liver regeneration in the cd39 null mouse.
* Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC. Adenosine generation by CD39 and CD73 on T regulatory cells mediates immune suppression. J. Exp. Med. 2007 Jun 11;204(6):1257-65. Epub 2007 May 14. The phenotype of T regulatory cells can be characterized by dual surface expression of CD39 and CD73, another ectonucleotidase that operates in tandem to generate adenosine. Adenosine can be shown to be immune suppressive in both in vitro and in vivo systems. Hence CD39 and purinergic mechanisms are closely implicated in regulatory T cell suppressive functions. See Nature reviews. DOI: 10.1038/nri2122
* Kaczmarek E, Koziak K, Sevigny J, Siegel JB, Anrather J, Beaudoin AD, Bach FH, Robson SC. Identification and characterization of vascular ATP diphosphohydrolase/CD39. J. Biol. Chem. 1996; 271: 33116-33122. This manuscript first documented that CD39, a previously obscure B lymphocyte activation marker, was in fact a vascular endothelial ecto-nucleotidase and responsible for the modulation of platelet reactivity. Ecto-nucleotidases were purified and sequenced from lung and pancreas tissues. These proteins were shown to have identity with CD39; recombinant proteins were generated and then functionally characterized as the vascular ATP diphosphohydrolase (later termed ecto-NTP diphosphohydrolase-1, NTPDase1 or ENTPD1).
* Robson SC, Kaczmarek E, Koziak K, Siegel JB, Millan M, Candinas D, Hancock WW, Bach FH. Loss of ATP diphosphohydrolase following endothelial cell activation. J. Exp. Med. 1997; 185: 153-163. This manuscript demonstrated that the biological activity of CD39/ATP diphosphohydrolase could be lost following exposure to oxidant stress reactions, both in vitro and in vivo. Expression of CD39 or administration of soluble derivatives appears to be crucial for the vascular integrity of transplanted injured grafts that have lost this thromboregulatory factor. The demonstration that CD39 activity could be lost from inflamed vasculature provided a theoretical foundation for therapeutic interventions. Hence, the generation of transgenic animals over-expressing CD39 to serve as organ donors in the area of xenotransplantation research and ultimately for either targeted genetic or pharmacological therapies (requiring soluble derivatives of the CD39 membrane ectoenzyme) that could be used in vascular inflammation.
* Enjyoji K, Sevigny J, Lin Y, Frenette PS, Christie PD, Schulte am Esch II J, Imai M, Edelberg JM, Rayburn H, Lech H, Beeler DL, Csizmadia E, Wagner DD, Robson SC & Rosenberg RD (joint senior authors). Targeted disruption of Cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nature Med. 1999; 5: 1010-1017. This collaborative venture was developed between MIT (Rosenberg) and Harvard (Robson). Experimentation resulted in the generation and characterization of the genetically manipulated mouse null for Cd39. The consequent analysis of the model system, and importantly this first CD39/NTPDase gene family deletion, culminated in this manuscript that details a dualistic role for CD39 in modulating P2 extracellular nucleotide receptor function in hemostatic, inflammatory and thrombotic reactions in vivo.
