Department of Microbiology and Immunology
Carl Atkinson, PhD
2004 – 2006 Post Doctoral Fellow, CRI , Medical University of South Carolina
2004 PhD, University of the West of England, Bristol, England
Heart transplantation is an accept treatment modality for patients with end-stage heart disease. These patients have reached the end of conventional pharmacological therapy or surgical interventions and the only therapeutic option left is heart transplantation. Current first year survival rates post transplantation varies between 80-95%, and patients surviving beyond the first can expect an average half-life of 11 years. While these results are acceptable patients eventually succumb to chronic rejection which manifests as an obliterative vascular lesion which restricts the hearts blood supply and eventually leads to heart failure. The precise mechanisms that contribute to the development of chronic rejection are unknown, but recent data implicates the early ischemic damage these hearts receive due to the transplant process and brain death.
Results from kidney transplantation have shown that the quality of the donor organ is important for post transplant survival. Organs donated from living donors perform better than those harvested from cadaveric donors. It is believed that the processes stimulated during brain death in these cadaveric donors, activates the donor heart rendering it more susceptible to ischemic damage, upon implantation, and ultimately acute and chronic rejection. The mechanisms responsible for these inflammatory changes to the donor organ are poorly characterized. Our research focuses on the elucidation of these mechanisms and the application of novel therapies that can be applied to the donor prior to transplantation to limit donor organ damage. During brain death all of the organs in the body are exposed to ischemia and chaotic changes in blood supply and pressure. Our studies have implicated the complement system in the activation of the donor heart. The complement system is composed of a series of serum proteins that work in a concerted fashion to induce cell death, promote inflammation and pro-inflammatory cytokines. We have been working with complement inhibitory proteins with the aim to reduce complement mediated brain death induced inflammation and ultimately to reduce the incidence and severity of both acute and chronic rejection.
Recent Publications | Additional Publications
Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology.
Arbra CA, Nadig SN, Dennis SG, Pattanaik S, Bainbridge HA, Rhett JM, Fann SA, Atkinson C, Yost MJ.
J Vis Exp. 2018 Mar 27;(133). doi: 10.3791/57358.
HDAC inhibition helps post-MI healing by modulating macrophage polarization.
Kimbrough D, Wang SH, Wright LH, Mani SK, Kasiganesan H, LaRue AC, Cheng Q, Nadig SN, Atkinson C, Menick DR.
J Mol Cell Cardiol. 2018 Apr 19;119:51-63. doi: 10.1016/j.yjmcc.2018.04.011. [Epub ahead of print]
Impact of Mitochondrial Permeability on Endothelial Cell Immunogenicity in Transplantation.
Tran DT, Esckilsen S, Mulligan J, Mehrotra S, Atkinson C, Nadig SN.
Transplantation. 2018 Mar 10. doi: 10.1097/TP.0000000000002163. [Epub ahead of print]
Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant.
Cheng Q, Patel K, Lei B, Rucker L, Allen DP, Zhu P, Vasu C, Martins PN, Goddard M, Nadig SN, Atkinson C.
Am J Transplant. 2018 Mar 5. doi: 10.1111/ajt.14717. [Epub ahead of print]
The role of regulatory T cells in the regulation of upper airway inflammation.
Palmer C, Mulligan JK, Smith SE, Atkinson C.
Am J Rhinol Allergy. 2017 Nov 1;31(6):345-351. doi: 10.2500/ajra.2017.31.4472.
Nanotechnological Approaches to Immunosuppression and Tolerance Induction.
Patel K, Atkinson C, Tran D, Nadig SN.
Curr Transplant Rep. 2017 Jun;4(2):159-168. doi: 10.1007/s40472-017-0146-9. Epub 2017 Apr 17.
Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.
Mulligan JK, Pasquini WN, Carroll WW, Williamson T, Reaves N, Patel KJ, Mappus E, Schlosser RJ, Atkinson C.
PLoS One. 2017 Oct 18;12(10):e0186374. doi: 10.1371/journal.pone.0186374. eCollection 2017.
Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice.
Marshall K, Jin J, Atkinson C, Alawieh A, Qiao F, Lei B, Chavin KD, He S, Tomlinson S.
Hepatology. 2017 Sep 7. doi: 10.1002/hep.29512. [Epub ahead of print]
Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency.
Beiko T, Janech MG, Alekseyenko AV, Atkinson C, Coxson HO, Barth JL, Stephenson SE, Wilson CL, Schnapp LM, Barker A, Brantly M, Sandhaus RA, Silverman EK, Stoller JK, Trapnell B, Charlie S.
Chronic Obstr Pulm Dis. 2017 Jul 15;4(3):204-216. doi: 10.15326/jcopdf.4.3.2016.0180.
Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury , drive secondary injury by activating complement.
Narang A, Qiao F, Atkinson C, Zhu H, Yang X, Kulik L, Holers VM, Tomlinson S.
J Neuroinflammation. 2017 Jun 19;14(1):120. doi: 10.1186/s12974-017-0894-6.
Impact of tobacco smoke on upper airway dendritic cell accumulation and regulation by sinonasal epithelial cells.
Mulligan JK, O'Connell BP, Pasquini W, Mulligan RM, Smith S, Soler ZM, Atkinson C, Schlosser RJ.
Int Forum Allergy Rhinol. 2017 Aug;7(8):777-785. doi: 10.1002/alr.21955. Epub 2017 Jun 2.
1UO1AI132894-01 Tomlinson/Atkinson (MPI) 07/01/17-6/30/22
Graft-targeted anti-complement therapy to reduce cardiac graft injury and allograft vasculopathy Goals of the study are to investigate the impact of ischemia reperfusion on the development of chronic rejection, and further to explore the ability of complement inhibition to impart tolerance induction or the application of immunosuppressive sparing regimes.
DOD RW81XWH-16-1-0783 Atkinson (PI) 07/01/16-6/30/18
Pre-transplant Complement Inhibitory Graft Therapy Enables Prolonged Cold Storage and Improved Outcomes in Vascularized Composite Allografts
To improve vascularized composite allograft cold storage through the application of novel targeted complement inhibitors applied to the brain dead donor.
Patterson-Barclay Foundation Atkinson/Nadig (MPI) 04/24/16-03/31/18
Merging Bioengineering and Immunology
To investigate novel methods of improving transplantation via bioengineering and immunology. Role: PI
R01 CA203628 Ogretmen (PI) 05/01/16-04/30/21 NIH/NCI
Development of Novel Cancer Therapeutics by Targeting Sphingolipid Signaling
To determine common signaling mechanisms regulated by sphingosine 1-phosphate (S1P) that induce cancer cell proliferation, resistance to therapy, and metastasis in solid tumors. The therapeutic goal is to utilize mechanistic information gained from these studies for the development of novel therapeutic strategies to treat patients with solid tumors by targeting pro-survival S1P signaling.
R01 DK102912 Tomlinson (PI) 07/01/15 - 06/30/19
Antibodies and Complement in Ischemia Reperfusion Injury Regeneration
To isolate and characterize natural antibodies that contribute to complement mediated ischemia reperfusion injury in models of liver ischemia and reperfusion injury.
K08 EB0109495-01A1 Nadig (PI) 04/01/16 - 03/31/19 NIH/NIBIB
Nanoparticle Therapy for Targeted Drug Delivery in Transplantation
To utilize complement split products that are inherently upregulated in a newly transplant organ as a target for focused nanoparticles delivering targeted immunosuppression in situ.