Research in the Spite Lab is focused on understanding how immune cells and parenchymal cells change their phenotypes during resolution of inflammation, and how these phenotypes govern subsequent phases of tissue repair and regeneration following injury. We are particularly interested in the role of receptors for pro-resolving lipid mediators in these processes and are determining how their expression is regulated, and how they function to modulate cellular phenotypic transitions. By elucidating the regulation and function of pro-resolving receptors in distinct cell types, we can begin to understand how their expression or downstream signaling might be altered in chronic inflammatory diseases, such as cardiovascular and metabolic diseases. The overall goal of our research is to determine whether activating pro-resolving receptors could prevent or reverse chronic inflammation and associated deficits in tissue repair and regeneration, leading to increased resilience in the face of persistent inflammatory triggers.
Selected Key Publications
Lipscomb M, Walis S, Marinello M, Mena HA, MacNamara KC, Spite M, Fredman G. Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18. (2024) FASEB J. Mar 31;38(6):e23555.
Walker ME, Kodani SD, Mena HA, Tseng YH, Cypess AM, Spite M. Brown adipose tissue activation in humans increases plasma levels of lipid mediators. (2024) J Clin Endocrinol Metab. 109:1837-1849
Levy ES, Kim AS, Werlin E, Chen M, Sansbury BE, Spite M, Desai TA, Conte MS. Tissue factor targeting peptide enhances nanoparticle binding and delivery of a synthetic specialized pro-resolving lipid mediator to injured arteries. (2023) JVS Vasc Sci. 4:100126.
Sugimoto S, Mena HA, Sansbury BE, Kobayashi S, Tsuji T, Wang CH, Yin X, Huang TL, Kusuyama J, Kodak SD, Darcy J, Profeta G, Pereira N, Tanzi RE, Zhang C, Serwold T, Kokkotou E, Goodyear LJ, Cypess AM, Leiria LO, Spite M*, Tseng YH. Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation. (2022) Nature Metabolism 4:775-79 *Co-corresponding author
Sansbury BE, Li X, Wong B, Patsalos A, Giannakis N, Zhang MJ, Nagy L, Spite M. Myeloid ALX/FPR2 regulates vascularization following tissue injury. (2020) Proc. Natl. Acad. Sci. U.S.A. 117:14354-14364
Giannakis N, Sansbury BE, Patsalos A, Hays TT, Riley CO, Han X, Spite M*, Nagy L Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration. (2019) Nature Immunology 20:765-767. *Co-corresponding author (See video highlight below)
Hellmann J, Sansbury BE, Wong B, Li X, Singh M, Nuutila K, Chiang N, Eriksson E, Serhan CN, Spite M. Biosynthesis of D-Series Resolvins in Skin Provides Insights into their Role in Tissue Repair. (2018) J Invest Dermatol. 138(9):2051-2060.
Zhang MJ, Sansbury BE, Hellmann J, Baker JF, Guo L, Parmer CM, Prenner JC, Conklin DJ, Bhatnagar A, Creager MA, Spite M Resolvin D2 enhances post-ischemic revascularization while resolving inflammation. (2016) Circulation 134:666-80.
Sansbury BE, Spite M. Resolution of acute inflammation and the role of resolvins in immunity, thrombosis and vascular biology. (2016) Circulation Research 119:113-30
Varga T, Mounier R, Patsalos A, Gogolak P, Peloquing M, Horvath A, Pap A, Daniel B, Nagy G, Pintye E, Poliska S, Cuvellier S, Larbi SB, Alvarado G, Sansbury BE, Spite M, Brown CW, Chazaud B, Nagy L. PPARγ in repair macrophages controls GDF3 and skeletal muscle regeneration. (2016) Immunity 45:1038-1051
Fredman G, Hellmann J, Proto J, Kuriakose G, Colas R, Dorweiler B, Connolly E, Solomon R, Heyer E, Jones D, Spite M*, Tabas I. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. (2016) Nature Communications 7:12859. *Co-corresponding author
Cai B, Thorp EB, Doran AC, Subramanian M, Sansbury BE, Lin CS, Spite M, Fredman G, Tabas I MerTK cleavage limits pro-resolving mediator biosynthesis and exacerbates tissue inflammation. (2016) Proc. Natl. Acad. Sci. 113:6526-31.
Spite M, Claria J, Serhan CN Resolvins, specialized pro-resolving lipid mediators and their potential roles in metabolic diseases. (2013) Cell Metabolism 19: 21-36
Tang Y, Zhang MJ, Hellmann J, Kosuri M, Bhatnagar A, Spite M Pro-resolving therapy for the treatment of delayed healing of diabetic wounds. (2013) Diabetes 62:618-27.
Spite M, Norling LV, Summers L, Yang R, Cooper D, Petasis NA, Flower RJ, Perretti M, Serhan CN. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. (2009) Nature 461:1287-1291.
Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M. Maresins: novel macrophage mediators with potent anti-inflammatory and pro-resolving actions. (2009) Journal of Experimental Medicine. 206: 15-23.
