長聘教軌副教授
表觀遺傳修飾在骨髓造血幹細胞的分化與命運決定中發揮了關鍵作用。 課題組前期研究結果表明外周炎性信號可顯著調控HSPC中表觀遺傳修飾介導的訓練免疫的形成。課題組將對外周炎性信號誘導下📖，HSPC內多種組蛋白修飾及mRNA的m6A甲基化修飾在全基因水平的分布變化進行分析，鑒定受表觀修飾調控的關鍵骨髓髓系分化及炎性相關基因及其重要表觀修飾位點，為抑製造血幹細胞水平訓練免疫的形成提供關鍵靶點。
在多種慢性疾病並存的情況下🔱，對單一疾病的治療很難達到理想的效果。 因此👩🏻🦳，在單一炎症的研究基礎上，深入解析慢性並發症的致病機製並確定關鍵致病因子🤵♂️，將為慢性並發症的治療提供新的治療思路和靶標。課題組的前期工作明確了炎性信號誘導的造血幹細胞水平的訓練免疫在慢性並發症發病中的重要作用。因此，本課題組致力於開發同時針對外周炎症及骨髓中訓練免疫的聯合療法🚵🏽♀️，從而有效地抑製外周炎症與骨髓之間的有害反饋回路🙃，限製慢性並發症的進展🐕👩💻。
炎症反應可保護人體免受病原體的入侵及外界刺激的傷害💇🏿，通常可自行消退。然而在特定條件下，炎症消退過程被抑製💂🏽，急性炎症發展為慢性炎性疾病，經久不愈。組織特異性穩態分子可在微環境中調節免疫細胞的豐度及功能，主動促進炎症的消退，最終恢復/維持組織的完整性和穩態。然而，迄今發現的主動促進炎症消退的組織特異性穩態分子數量十分有限🧕🏼，亟需深入探索🫄🏼。
Xiaofei Li*, Hui Wang*, Xiang Yu, Gundappa Saha, Lydia Kalafati, Charalampos Ioannidis, Ioannis Mitroulis, Mihai G Netea, Triantafyllos Chavakis, George Hajishengallis. Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities. Cell, 2022 May 12;185(10):1709-1727.e18.
Ioannis Kourtzelis*, Xiaofei Li*, Ioannis Mitroulis, Daniel Grosser, Tetsuhiro Kajikawa, Baomei Wang, Michal Grzybek, Janusz Von Renesse, Aleksander Czogalla, Maria Troullinaki, Anaisa Ferreira, Christian Doreth, Klara Ruppova, Lan-Sun Chen, Kavita Hosur, Jong-Hyung Lim, Kyoung-Jin Chung, Sylvia Grossklaus, Anne Kathrin Tausche, Leo AB Joosten, Niki M Moutsopoulos, Ben Wielockx, Antonio Castrillo, Jonathan M Korostoff, Ünal Coskun, George Hajishengallis, Triantafyllos Chavakis. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat. Immunol. 2019 Jan;20(1):40-49.
Xiaofei Li*, Alessandra Colamatteo*, Lydia Kalafati, Tetsuhiro Kajikawa, Hui Wang, Jong-Hyung Lim, Khalil Bdeir, Kyoung-Jin Chung, Xiang Yu, Clorinda Fusco, Antonio Porcellini, Salvatore De Simone, Giuseppe Matarese, Triantafyllos Chavakis, Veronica De Rosa, George HajishengallisThe DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution. J Clin Invest. 2020 Dec 1; 130(12): 6261–6277.
George Hajishengallis#, Xiaofei Li#, Triantafyllos Chavakis#. Immunometabolic control of hematopoiesis. Mol. Asp. Med. 2021 Feb;77:100923.
Lydia Kalafati, Ioannis Kourtzelis, Jonas Schulte-Schrepping, Xiaofei Li, Aikaterini Hatzioannou, Tatyana Grinenko, Eman Hagag, Anupam Sinha, Canan Has, Sevina Dietz, Antonio Miguel de Jesus Domingues, Marina Nati, Sundary Sormendi, Ales Neuwirth, Antonios Chatzigeorgiou, Athanasios Ziogas, Mathias Lesche, Andreas Dahl, Ian Henry, Pallavi Subramanian, Ben Wielockx, Peter Murray, Peter Mirtschink, Kyoung-Jin Chung, Joachim L Schultze, Mihai G Netea, George Hajishengallis, Panayotis Verginis, Ioannis Mitroulis, Triantafyllos Chavakis. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020 Oct 29;183(3):771-785.e12.
Hui Wang, Xiaofei Li, Tetsuhiro Kajikawa, Jieun Shin, Jong-Hyung Lim, Ioannis Kourtzelis, Kosuke Nagai, Jonathan M Korostoff, Sylvia Grossklaus, Ronald Naumann, Triantafyllos Chavakis, George Hajishengallis. Stromal cell–derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis. J. Clin. Investig. 2021 Oct 1;131(19):e150578.
Da-Yo Yuh, Tomoki Maekawa, Xiaofei Li, Tetsuhiro Kajikawa, Khalil Bdeir, Triantafyllos Chavakis, George Hajishengallis. The secreted protein DEL-1 activates a β3 integrin–FAK–ERK1/2–RUNX2 pathway and promotes osteogenic differentiation and bone regeneration. J. Biol. Chem. 2020 May 22;295(21):7261-7273.
論文下載
支撐材料