Dr. Lai, Shih-Lei 賴時磊 博士

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Dr. Lai, Shih-Lei
賴時磊 博士

Assistant Research Fellow
助研究員

  • Inst. of Zoology, National Taiwan University. Ph.D.

    Inst. of Fisheries Science, National Taiwan University. M.S. program

    Dept. of Biology, Fu-Jen Catholic University. B.Sc.

  • 886-2-26523057 (Office)
  • ben.s.lai@ibms.sinica.edu.tw
Specialty:

Cardiac repair and regeneration

Cardiovascular development and disease

Developmental genetics using zebrafish model

RESEARCH

Heart failure is a major cause of morbidity and mortality, in part because of the inability of the human heart to replenish lost tissue post myocardial infarction (MI).  

Unlike adult mice and humans, many vertebrates, including certain fish and amphibians, are capable of endogenous heart regeneration at adult stages.  While zebrafish exhibits a remarkable regenerative capacity after various cardiac insults, this ability is not shared by another teleost, the medaka, despite medaka has similar anatomic structure, physiological conditions and living environment.  In order to identify cellular and molecular bases for this difference, we performed comparative analyses in zebrafish and medaka following cardiac cryoinjury.  Transcriptomic comparisons point to major differences in immune response and angiogeneic neovascularization between these models.  Our functional studies indeed highlighted the complex role of the immune response and neovascularization during cardiac regeneration, and serve as a platform for identifying and testing additional regulators of cardiac repair.

Our primary focus is to investigate the differential immune responses in regenerative (e.g. zebrafish and neonatal mice) and non-regenerative models (e.g. medaka and adult mice), and translate the knowledge into potential therapeutics to modulate the immune response and improve cardiac repair in patients suffered from MI.

研究介紹

人類心肌梗塞導致心肌壞死後(俗稱心臟病),死亡的心肌細胞無法再生。取而代之的結締組織會影響心臟功能、進一步導致心室肥大、心臟衰竭,與患者死亡;不同於哺乳類,許多演化上較原始的脊椎生物例如部分魚類與兩生類,在心肌壞死後仍保有再生能力,能夠完美的恢復組織型態與功能。

本實驗室以系統生物學與功能性基因體學的方式,結合多種模式生物探討脊椎動物心臟受損後的修復與再生機制。其中,斑馬魚與稻田魚同為淡水硬骨魚,具有相同的解剖構造、生理條件與生活環境。令人意外地,稻田魚在心肌受損後卻無法活化心肌再生。基於哺乳類與魚類在各方面的巨大差異,稻田魚與斑馬魚的對比提供絕佳的模式來探討心臟再生的關鍵因子。目前主要的研究方向是比較分析斑馬魚與稻田魚在組織受損後的基因轉錄反應(transcriptome)有何不同,以期增進我們對心臟再生的了解並進而轉譯這些知識到臨床治療,改善人類心臟病的預後。

我們的初步研究發現免疫反應與組織血管新生在這兩種模式生物中有明顯的不同。其中,巨噬細胞(macrophage)在這兩種模式生物的比較中扮演非常重要且不同的功能。在斑馬魚心臟受損時,巨噬細胞的入侵速度與數量似乎比在稻田魚心臟受損時快且多。減緩巨噬細胞在心臟受損後入侵傷處的速度竟會完全阻礙斑馬魚的心臟再生能力,即使晚到的巨噬細胞能夠達到一樣多的數目,暗示其功能特性已改變(polarity);反之,簡單的注射免疫觸發物poly I:C竟能夠有效的活化巨噬細胞的入侵、並促進稻田魚的心臟再生。我們對這樣的結果感到非常興奮,並將積極地進一步探討背後的機制、以及轉譯這些知識到臨床治療。

PUBLICATIONS 研究論文

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