Professor and Interim Chair, Microbiology & Immunology
1990-1991 Postdoctoral Fellow, Dept. of Molecular Biology, University of Florida at Gainesville
Our lab investigates the biology of the complement system, with a focus on its role in inflammation and the shaping of adaptive immunity. Our disease focus is brain injury (stroke and traumatic brain injury) and transplantation (cardiac and vascularized composite allograft, or face/limb transplantation). In the context of brain injury, we investigate how complement is involved in neuroinflammation and neurodegeneration (including dementia), as well as its role in neuroregenerative and repair mechanisms. A current interest is the complement-glia-neuronal axis under homeostatic and pathologic conditions. We also incorporate clinical studies through collaborations with clinicians. In the context of transplantation, we are interested in how complement modulates inflammation following donor brain death, and acutely in the recipient following transplantation. How these early innate immune reactions modulate the subsequent development of an alloimmune response is also under investigation. Our lab has developed a unique and expanding set of site-targeted complement inhibitors that specifically recognize stress and injured tissue (eg. in the brain after injury or in the graft after transplantation), and that can modulate different pathways of complement activation. We use these inhibitors as a toolbox to investigate complement-dependent mechanisms, but are also investigating novel therapeutic approaches. With regard to the latter, the laboratory is involved in various entrepreneurial and commercialization activities.
Publications (selected from >150) | Additional Publications
Tomlinson S, Thurman JM. Tissue-targeted complement therapeutics.Mol Immunol. 2018 Oct;102:120-128. doi: 10.1016/j.molimm.2018.06.005. Epub 2018 Jul 7. PMID: 30220307
Alawieh A, Andersen M, Adkins DL, Tomlinson S. Acute Complement inhibition potentiates neurorehabilitation and enhances tPA-mediated neuroprotection. J Neurosci. 2018 Jun 19. pii: 0111-18. doi: 10.1523/JNEUROSCI.0111-18.2018. [Epub ahead of print] PMID: 29921716
Alawieh A, Langley EF, Tomlinson S. Targeted complement inhibition salvages stressed neurons and inhibits neuroinflammation after stroke in mice. Sci Transl Med. 2018 May 16;10(441). pii: eaao6459. doi: 10.1126/scitranslmed.aao6459. PMID:29769288
Alawieh A, Langley EF, Weber S, Adkins D, Tomlinson S. Identifying the role of complement in triggering neuroinflammation after traumatic brain injury. J Neurosci. 2018 Feb 6. pii: 2197-17. doi: 10.1523/JNEUROSCI.2197-17.2018. [Epub ahead of print] PMID:29437855
Marshall K, Jin J, Atkinson C, Alawieh A, Qiao F, Lei B, Chavin KD, He S, Tomlinson S. Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice. Hepatology. 2017 Sep 7. doi: 10.1002/hep.29512. [Epub ahead of print] PMID:28880403
Alawieh A, Tomlinson S, Adkins D, Kautz S, Feng W. Preclinical and Clinical Evidence on Ipsilateral Corticospinal Projections: Implication for Motor Recovery. Transl Stroke Res. 2017 Dec;8(6):529-540. doi: 10.1007/s12975-017-0551-5. Epub 2017 Jul 9. Review. PMID:28691140
Narang A, Qiao F, Atkinson C, Zhu H, Yang X, Kulik L, Holers VM, Tomlinson S. Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury , drive secondary injury by activating complement. J Neuroinflammation. 2017 Jun 19;14(1):120. doi: 10.1186/s12974-017-0894-6. PMID:28629465
Schnabolk G, Beon MK, Tomlinson S, Rohrer B. New Insights on Complement Inhibitor CD59 in Mouse Laser-Induced Choroidal Neovascularization: Mislocalization After Injury and Targeted Delivery for Protein Replacement. J Ocul Pharmacol Ther. 2017 Jun;33(5):400-411. doi: 10.1089/jop.2016.0101. Epub 2017 Mar 23. PMID:28333572
Long X, Cheng Q, Liang H, Zhao J, Wang J, Wang W, Tomlinson S, Chen L, Atkinson C, Zhang B, Chen X, Zhu P. Memory CD4+ T cells are suppressed by CD8+ regulatory T cells in vitro and in vivo. Am J Transl Res. 2017 Jan 15;9(1):63-78. eCollection 2017. PMID:28123634
Zhu P, Bailey SR, Lei B, Paulos CM, Atkinson C, Tomlinson S. Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy. Transplantation. 2017 Apr;101(4):e75-e85. doi: 10.1097/TP.0000000000001625. PMID:28045880
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. PMID:27913437
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. Aberrant JMJD3 Expression Upregulates Slug to Promote Migration, Invasion, and Stem Cell-Like Behaviors in Hepatocellular Carcinoma. Cancer Res. 2016 Nov 15;76(22):6520-6532. doi: 10.1158/0008-5472.CAN-15-3029. Epub 2016 Sep 20. PMID:27651311
Alawieh A, Tomlinson S. Injury site-specific targeting of complement inhibitors for treating stroke. Immunol Rev. 2016 Nov;274(1):270-280. doi: 10.1111/imr.12470. Review. PMID:27782326
29 invention disclosures and 162 patent applications in more than 50 countries, with 80 patents issued.
1I01RX001141 Tomlinson (PI) 04/01/14-03/30/22
VA/RR&D Merit Award $221,000
Impacts of comorbidities on stroke outcomes and treatments
The major goals of this project are to investigate how age and cigarette smoke exposure impact post-stroke inflammation and long-term recovery.
RX002363 Tomlinson (PI) 01/01/19-12/31/22
VA/BLRD Merit Award $275,000
Role of complement in TBI
The major goals of this project are to investigate how complement modulates secondary injury after TBI, and the interaction of complement with microglia.
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 $100,000/year
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 1.8 CM (MUSC)
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) 7/1/2016 – 4/30/2020 0.3 CM (MUSC)
NIH (Subaward with Temple University) $35,484/year
Atherogenic Role of Complement System
To provide complement inhibitory reagents and analyze CD59 involvement in atherogenesis.
1U01AI132894 Tomlinson (coPI) 07/1/17-06/30/22 1.8 CM (MUSC)
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) 07.01/17-06/30/22 0 CM (MUSC)
Program in Immunology Research and Entrepreneurship (PIRE)
DOD. Concept Award (Tomlinson, PI) 8/1/19-1/31/21 1.2 CM (MUSC) $133,000 (total)
Preventing rejection of vascularized composite allografts using novel graft-targeting chimeric antigen receptor T regulatory cells.
DOD. Investigator Initiated Award (Tomlinson, PI) 8/1/19-7/31/22 1.2 CM (MUSC) $668,498 (total)
Modulating inflammation to improve existing therapies and outcomes