Department of Surgery
Satish Nadig, MD, PhD Research
|Left to right: Peng Zhu, Will Dennis, |
Satish Nadig, MD, PhD, Natalie Levey
*Not pictured Alister Wilton and Kunal Patel
Organ transplantation has become an accepted modality for the treatment of end-stage organ failure. The field of transplant medicine has made tremendous strides within the last thirty years, allowing for newer, more potent immunosuppressive medications rendering acute rejection episodes less frequent and less aggressive. In spite of these accomplishments, chronic rejection remains a leading cause of graft loss in the long term. Various translational research efforts have identified pathways and potential therapeutics that may allay the effects of chronic rejection by conferring a tolerogenic phenotype in allograft recipients both in mouse and man.
Cellular therapies including the use of particular subsets of CD4+ T cells expressing the markers CD25hi CD127lo FOXP3+ have been termed “regulatory T cells (Treg)” for their innate suppressive capacity. These Treg have enjoyed much attention in the literature for their natural and adaptive ability to suppress alloantigenic immune responses and provide long-term graft survival in various mouse and humanized experimental models. Harnessing the suppressive capacity of Treg and applying them to the clinic is under vigorous investigation at present, and is now in early stages of clinical trials. Additionally, various pharmacotherapeutics have been shown to bolster the natural suppressive capacity of these Treg.
In addition to the study of Treg biology, our lab is dedicated to the study of Novel Investigations in Transplantation Tolerance (NITT). As the NITT group, we are interested in various innovative methods focused on the study of tolerance induction in transplanted allografts. Currently, we are investigating drug delivery techniques including the use of nanoparticles for targeted drug delivery, methods of personalizing immunosuppression, as well as the utilization of humanized mouse models in pre-clinical in vivo assays.
Selected Publications (full CV may be viewed in the faculty profile related links):
1. Satish N. Nadig*, Joanna Więckiewicz*, Douglas C. Wu, Gregor Warnecke, Wei Zhang, Shiqao Luo, David P. Taggart, and Kathryn J. Wood. In vivo Prevention of Transplant Arteriosclerosis by ex vivo Expanded Human Regulatory T Cells. Nature Med. 2010 Jul;16(7):809-13 Click Below for editorial in Science-Business Exchange (SciBx)
2. Gang Feng, Satish N. Nadig, Liselotte Backdahl, Stefan Beck, Ross S. Francis, Alexandru Schiopu, Kathryn J. Wood, and Andrew Bushell. Ex vivo T cell reprogramming by inhibition of PDE3 produces functional regulatory T cells that prevent transplant rejection. Science-TM. 2011; May 18 3(83).
3. Fadi Issa, Joanna Hester, Ryoichi Goto, Satish N. Nadig, Tim Goodacre, and Kathryn Wood. Ex-vivo expanded human regulatory T cells prevent the rejection of skin allografts in a humanized mouse model. Transplantation. 2010 Dec 27;90(12):1321-7
4. Alexandru Schiopu, Satish N. Nadig, Ovidiu S. Cotoi, Joanna Hester, Nico Van Rooijen, and Kathryn J. Wood. Inflammatory Ly-6Chi monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients. Atherosclerosis. 2012 Aug;223(2):291-8.
5. Joanna Hester, Alexandru Schiopu, Satish N. Nadig, and Kathryn J. Wood. Low dose rapamycin treatment increases the ability of human regulatory T cells to inhibit transplant arteriosclerosis in vivo. American Journal of Transplantation. 2012; Aug; 12(8):2008-16.
6. Douglas Wu, Joanna Hester, Satish Nadig, Wei Zhang, Piotr Trzonkowski, Derek Gray, Paul Johnson and Kathryn J. Wood. Ex vivo expanded human CD25highCD4+ regulatory T cells can prolong survival of a human islet allograft in a humanized mouse model. Transplantation. Transplantation. 2013 Aug.
7. Satish N. Nadig MD, Basker Periyasamy MD, Stephen F. Shafizadeh DC, Carmen Polito BS, Ryan Fiorini BS, David Rodwell BS, Zachary Evans BS, Gang Cheng MD PhD, Dana Dunkelberger PhD, Michael Schmidt PhD, Sally E. Self MD, Kenneth D. Chavin MD, PhD. Hepatocellular ultrastructure after ischemia/reperfusion injury in human orthotopic liver transplantation. Journal of Gastrointestinal Surgery. 2004; 8(6): 695-700
8. Gregor Warnecke, Andrew Bushell, Satish N. Nadig, and Kathryn J. Wood. Regulation of Transplant Arteriosclerosis by CD25+CD4+ T cells Generated to Alloantigen In Vivo. Transplantation. 2007; Jun 15.83(11):1459-1465.
9. Cherry I. Kingsley*, Satish N. Nadig*, Kathryn J. Wood. Transplantation Tolerance: Lessons from Experimental Rodent Models. Transplant International. 2007 Oct;20(10):828-41
10. Gregor Warnecke*, Gang Feng*, R. Goto, Satish N. Nadig, Ross Francis, Andrew Bushell, and Kathryn J. Wood. CD4+ Regulatory T cells generated in vitro with IFN-γ and Allogeneic APC inhibit transplant arteriosclerosis. Am. J. Path. 2010 Jul;177(1):464-72.
11. Satish N. Nadig MD, Charles F. Bratton MD, and Seth Karp MD. Marginal Donors in Liver Transplantation: Expanding the Donor Pool. Current Surgery. 2007;64(1): 46-50