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 | Additional Publications
Acute Complement inhibition potentiates neurorehabilitation and enhances tPA-mediated neuroprotection.
Alawieh A, Andersen M, Adkins DL, Tomlinson S.
J Neurosci. 2018 Jun 19. pii: 0111-18. doi: 10.1523/JNEUROSCI.0111-18.2018. [Epub ahead of print]
Targeted complement inhibition salvages stressed neurons and inhibits neuroinflammation after stroke in mice.
Alawieh A, Langley EF, Tomlinson S.
Sci Transl Med. 2018 May 16;10(441). pii: eaao6459. doi: 10.1126/scitranslmed.aao6459.
Identifying the role of complement in triggering neuroinflammation after traumatic brain injury.
Alawieh A, Langley EF, Weber S, Adkins D, Tomlinson S.
J Neurosci. 2018 Feb 6. pii: 2197-17. doi: 10.1523/JNEUROSCI.2197-17.2018. [Epub ahead of print]
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]
Preclinical and Clinical Evidence on Ipsilateral Corticospinal Projections: Implication for Motor Recovery.
Alawieh A, Tomlinson S, Adkins D, Kautz S, Feng W.
Transl Stroke Res. 2017 Dec;8(6):529-540. doi: 10.1007/s12975-017-0551-5. Epub 2017 Jul 9. Review.
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.
New Insights on Complement Inhibitor CD59 in Mouse Laser-Induced Choroidal Neovascularization: Mislocalization After Injury and Targeted Delivery for Protein Replacement.
Schnabolk G, Beon MK, Tomlinson S, Rohrer B.
J Ocul Pharmacol Ther. 2017 Jun;33(5):400-411. doi: 10.1089/jop.2016.0101. Epub 2017 Mar 23.
Memory CD4+ T cells are suppressed by CD8+ regulatory T cells in vitro and in vivo.
Long X, Cheng Q, Liang H, Zhao J, Wang J, Wang W, Tomlinson S, Chen L, Atkinson C, Zhang B, Chen X, Zhu P.
Am J Transl Res. 2017 Jan 15;9(1):63-78. eCollection 2017.
Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy.
Zhu P, Bailey SR, Lei B, Paulos CM, Atkinson C, Tomlinson S.
Transplantation. 2017 Apr;101(4):e75-e85. doi: 10.1097/TP.0000000000001625.
Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer.
Metelli A, Wu BX, Fugle CW, Rachidi S, Sun S, Zhang Y, Wu J, Tomlinson S, Howe PH, Yang Y, Garrett-Mayer E, Liu B, Li Z.
Cancer Res. 2016 Dec 15;76(24):7106-7117. Epub 2016 Oct 20.
Aberrant JMJD3 Expression Upregulates Slug to Promote Migration, Invasion, and Stem Cell-Like Behaviors in Hepatocellular Carcinoma.
Tang B, Qi G, Tang F, Yuan S, Wang Z, Liang X, Li B, Yu S, Liu J, Huang Q, Wei Y, Zhai R, Lei B, Yu H, Tomlinson S, He S.
Cancer Res. 2016 Nov 15;76(22):6520-6532. doi: 10.1158/0008-5472.CAN-15-3029. Epub 2016 Sep 20.
Injury site-specific targeting of complement inhibitors for treating stroke.
Alawieh A, Tomlinson S.
Immunol Rev. 2016 Nov;274(1):270-280. doi: 10.1111/imr.12470. Review.
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.
1I01RX001141-05A1 Tomlinson (PI) 10/1/18-9/30/22
VA/RR&D Merit Award
Impact of Comorbidities on Stroke Outcomes and Treatments
The major goals of this project are to investigate how cigarette smoking and age affect acute and chronic complement-dependent neuroinflammation after stroke, and include both murine studies and clinical studies utilizing samples from stroke patients.
RO1DK102912 Tomlinson (PI) 07/01/15-06/30/19
Antibodies and complement in ischemia reperfusion injury and regeneration.
The major goals of this project are to investigate how IgM activates complement in the liver after hepatic insult, and how complement activation products, in particular the terminalmembrane attack complex, are involved in the balance between hepatic injury and the hepatocyte proliferative response after ischemia and liver resection.
1l21RX002363 Tomlinson (PI) 01/01/17-12/31/18
VA/RR&D SPIRE Award
Targeting complement and chronic inflammation after traumatic brain injury
Goal is to investigate how complement inhibitory therapy modulates rehabilitation-induced neural plasticity and recovery after traumatic brain injury in a mouse model.
R21NS097653 Tomlinson (PI) 04/01/17-03/31/20
Complement inhibitors targeted to the ischemic brain for the treatment of stroke
This is a “INNOVATION GRANTS TO NURTURE INITIAL TRANSLATIONAL EFFORTS” proposal that aims to characterize different approaches to target complement inhibitors to the post-ischemic brain, and to perform preclinical characterization of an identified lead molecule for subsequent commercialization efforts.
R01HL130233 (Qin) (Sub PI, Tomlinson) 07/01/16 – 4/30/20
NIH (Subaward with Temple University)
Atherogenic Role of Complement System
To provide complement inhibitory reagents and analyze CD59 involvement in atherogenesis.
DOD RW81XWH-16-1-0783 Tomlinson (co-I) 07/01/16-06/30/18
Pre-transplant Complement Inhibitory Graft Therapy Enables Prolonged Cold Storage and Improved Outcomes in Vascularized Composite Allografts
To improve vascularized composite allograft cold storage and investigate the role of P-selectin and complement inhibitory strategies by organ perfusion.
1U01AI132894 Tomlinson (coPI) 07/01/17-06/30/22
Graft-targeted anti-complement therapy to reduce cardiac graft injury and allograft vasculopathy
Aims are to investigate how brain death injury and ischemia reperfusion injury of heart grafts are modulated by antibodies and the complement system, with characterization of inhibitory strategies in a humanized mouse model
1T32AI132164 Tomlinson (PI) 0701/17-06/30/22
Program in Immunology Research and Entrepreneurship (PIRE)
This program will provide cutting-edge research and entrepreneurial training to a new generation of biomedical researchers.