Department of Microbiology and Immunology
Steve Tomlinson, PhD
1990-1991 Postdoctoral Fellow, Dept. of Molecular Biology, University of Florida at Gainesville
1989 Ph.D., University of Cambridge, UK
Complement is a group of about 50 soluble and cell surface proteins that represent a crucial component of both the innate and adaptive immune systems. Research in the laboratory is focused on the biology of the complement system, and how it modulates an inflammatory response and shapes adaptive immunity. Within the context of complement-modulated immunity, areas of study relate to ischemic injury and disease (such as stroke, spinal cord injury and post-transplant ischemia reperfusion injury), alloimmunity (transplant rejection) and cancer immunity. A further area of study is the dual role of complement in liver injury and regeneration, important in the context of liver resection or small-for-size transplant. Integrated within these studies is the development and characterization of various site-targeted strategies for complement inhibition. These strategies (some of which are in clinical development) are being investigated in various mouse models of injury and disease.
Publications (selected from 134) | Additional Publications
Varela JC, Imai M, Atkinson C, Ohta R, Rapisardo M, and Tomlinson S. (2008) Modulation of protective T cell immunity by complement inhibitor expression on tumor cells. Cancer Res 68:6734-42.
He S, Atkinson C, Qiao F, Cianflone K, Chen X, and Tomlinson S. (2009) A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration, and clinical implications. J Clin Invest 119:2304-16.
Atkinson C, Mosely E, Varela JC, Stoica S, Large S, Goddard M, and Tomlinson S. (2009) Complement dependent inflammation and Injury in a murine model of brain dead donor hearts. Circ Research 105:1094-1101. PMCID: PMC2783176
Atkinson C, He S, Morris K, Qiao F, Casey S, Goddard M, and Tomlinson S. (2010) Targeted complement inhibitors protect against post-transplant cardiac ischemia and reperfusion injury and reveal an important role for the alternative pathway of complement activation. J Immunol 185:7007-7013. PMID: 20962256
Elvington A, Atkinson C, Kulik L, Zhu H, Yu J, Kindy MS, Holers VM, and Tomlinson S. (2012) Pathogenic natural antibodies propagate cerebral injury following ischemic stroke in mice. J Immunol 188:14660-8.
Elvington M, Huang Y, Morgan BP, Qiao F, van Rooijen N, Atkinson C, and Tomlinson S. (2012) A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer. Blood 119:6043-51.
Elvington A, Atkinson C, Zhu H, Yu J, Takahashi K, Stahl GL, Kindy MS, and Tomlinson S. (2012) The alternative complement pathway propagates inflammation and injury in murine ischemic stroke. J Immunol 189:4640-7.
Holers VM, Rohrer B, and Tomlinson S. (2013) CR2-mediated targeting of complement inhibitors: bench-to-bedside using a novel strategy for site-specific complement modulation. Adv Exp Med Biol 734:137-54.
Atkinson C, Floerchinger B, Qiao F, Casey S, Williamson T, Mosely E, Stoica S, Goddard M, Ge X, Tullius SG, and Tomlinson S. (2013) Donor brain death exacerbates complement-dependent ischemia reperfusion injury in transplanted hearts. Circulation 127:1290-9.
Elvington M, Scheiber M, Yang X, Lyons K, Jacqmin D, Wadsworth C, Marshall D, Vanek K, and Tomlinson S. (2014) Complement dependent modulation of anti-tumor immunity following radiation therapy. Cell Reports 8:818-30.
Marshall KM, He S, Zhong Z, Atkinson C, and Tomlinson S. (2014) Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy. J Exp Med 211:1793-1805.
Elvington M, Schepp-Berglind J, and Tomlinson S. (2015) Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of DSS-induced colitis. Clin Exp Immunol 179:500-5008.
Alawieh A, Elvington A, and Tomlinson S. (2015) Complement in the homeostatic and ischemic brain. Front Immunol 6:417.
Atkinson C, Qiao F, Yang X, Peng Z, Reaves N, Kulik L, Goddard M, Holers VM, and Tomlinson S. (2015) Targeting pathogenic post-ischemic self-recognition by natural IgM to protect against post-transplant cardiac reperfusion injury. Circulation 131:1171-80.
Patents (153 filed, 53 issued)
Gilkeson, Gary; Holers, V. Michael; Tomlinson, Stephen; Rohrer, Baerbel. Targeting Complement Factor H for Treatment of Diseases. US, Patent 7,759,304, filed June 21, 2007, and issued July 20, 2010.
Tomlinson, Stephen; He, Songqing; Atkinson, Carl. Methods of Stimulating Liver Regeneration. US, Patent 2012-0171206 A1, filed December 22, 2011, and issued December 22, 2011.
Tomlinson, Stephen; Quigg, Richard. Tissue Targeted Complement Modulators. US, Patent 8,454,963, filed April 28, 2005, and issued June 4, 2013.
Holers, V. Michael; Tomlinson, Stephen. Complement Receptor 2 Targeted Complement Modulators. US, Patent 8,007,804, filed November 13, 2003, and issued August 30, 2013.
Holers, V. Michael; Tomlinson, Stephen; Thurman, Joshua; Kulik, Liudmila. Antibodies to the C3D Fragment of Complement Component 3. US, Patent Application , filed August 17, 2012, patent pending.
Holers, V. Michael; Tomlinson, Stephen; Rohrer, Baerbel; Thurman, Joshua; Kulik, Liudmila; Atkinson, Carl. Targeting Constructs Based on Natural Anitbodies and Uses Thereof. US, Patent Application , filed August 17, 2012, patent pending.
RO1 DK102912, Tomlinson (PI) 7/1/15-6/30/19
Antibodies and complement in ischemia reperfusion injury and regeneration.
Aims are to determine mechanisms of complement activation after insult to the liver, and the dual role of complement injury and regeneration mechanisms.
RO1 RCA158179, Tomlinson (PI) 10/1/12-9/30/17
Complement, anti-tumor immunity and apoptosis-based therapy
Aims are to investigate how complement modulates anti-tumor immunity after radiotherapy.
R56 AI119026, Tomlinson (PI) 9/5/15-8/31/16
Immune sensing of ischemic injury and complement-dependent modulation of alloimmunity in cardiac transplantation
Aims are to investigate expression profiles of danger associated molecular patterns in transplanted hearts and how they relate to ischemia reperfusion injury and subsequent acute rejection of grafts.
RRD Merit Award 1I101 RX00114, Tomlinson (PI) 4/1/14-3/30/18
Dept. Veterans Affairs
Novel therapies to improve functional recovery after stroke
Aims are to investigate neoepitopes expressed in the brain and how their recognition by complement-activating natural IgM antibodies drives post-stroke pathology using MCAO and micro-embolic murine models.
1P20GM109040-01 (Tomlinson, project leader) 12/1/14 -11/30/15
South Carolina Research Center for Recovery from Stroke
Complement-Dependent Inflammation and Experience-Dependent Neural Plasticity After Stroke
-Aims to investigate whether complement inhibition and rehabilitative therapy synergize to improve outcome after stroke. This small pilot grant provided the preliminary data shown in this R21 application.