回(in English)

Navigating Immunity: Zheng’s Academic Adventure 

(Part 1)

取材先 Interviewee:Zheng Zhiqian (Zheng), Division of Stem Cell and Molecular Medicine, Department of Computational Biology and Medical Sciences, D1 

インタビュアー Interviewer:Li Yang (Yang), Department of Computational Biology and Medical Sciences, D3

第7回、第8回はインタビュアー、取材先とも留学生による英文の記事です。留学生目線での対話をお楽しみ下さい。

This interview touches on Zheng-san’s steadfast academic journey, exploring intriguing and important cell interactions within our immune system. Discover her research objectives and insights into life at UTokyo on her PhD journey. Dive into the conversation for more!

【Part 1】Use animal models to study immune cells! 免疫細胞の研究に動物モデル!

Yang: Tell me about your research.

Zheng: Our lab primarily focuses on hematopoietic stem cells (HSCs, 造血幹細胞). Currently, my work is centered on studying the interactions between HSCs and CD8+ T cells.

Yang: Are these all types of blood cells?

Zheng: Yes. HSCs are responsible for generating all the different types of blood cells within our body. T cells are a specific type of immune cell (免疫細胞), comprising various subtypes such as helper T cells (CD4+ T cells, ヘルパーT細胞) and cytotoxic T cells (CD8+ T cells, 細胞傷害性T細胞).

Yang: So, the names CD4 and CD8 refer to different protein expressions on the surface of T cells, right?

Zheng: Exactly, and they have different functions. CD8+ T cells are commonly called cytotoxic T cells because of their ability to directly eliminate abnormal cells like tumor cells (腫瘍細胞).

Yang: What aspects of interactions between HSCs and CD8+ T cells are you investigating?

Zheng: I want to uncover whether CD8+ T cells have a direct killing effect on HSCs. This topic hasn’t been explored before. Have you heard of CAR T-cell therapy?

Yang: Yes! So far, it’s mainly used to treat blood cancer, right? It involves enhancing T cells through bioengineering to make them more potent against cancer.

Zheng: Precisely. However, current CAR T-cell therapy (CAR-T細胞療法) faces a significant challenge­­­––high relapse rates (高再発率). This is primarily because these therapies target downstream blood cells like B cells, rather than their precursor cells (前駆細胞) like HSCs or progenitor cells. If the disease is caused by mutant precursor cells, which is often the case, the mutant precursor cells can continue producing diseased offspring cells (子細胞), which leads to relapse.

Yang: I see. By directing T cells to target both the progenitors and HSCs, the effectiveness of CAR T-cell therapy could be improved.

Zheng: Right, that’s what I am working on. 

HSC cocultured with CD8+ T cell.

Green: live HSC. Red: dying HSC. Unlabeled: CD8+ T cell. 

Yang: It’s a fascinating and critical area of study. What is your approach?

Zheng: I use animal models (動物モデル), mainly mouse models, to validate my hypotheses. For instance, I isolate the CD8+ T cells out from one mouse and relocate them – this is called adoptive transfer (移植) – into other mice to observe whether they exhibit a killing effect on HSCs. Sometimes, I perform cell culture experiments to assess their killing capabilities in vitro.

Yang: It sounds quite intricate and challenging.

Zheng: Indeed, the experiments with mice are quite extensive. Sometimes I need to spend a whole day doing just one experiment.  

Doing experiments at the clean bench 

Yang: It’s admirable that you are so dedicated and more importantly, not afraid of animal experiments!

Zheng: I was, initially. I still remember my first animal experiment during my undergraduate years. I was uncertain about how to handle the mice. Over time, I’ve grown more accustomed to it, and things have become much smoother.

Yang: What has been the most enjoyable part of your PhD journey?

Zheng: I really enjoy doing experiments. There is this satisfaction in planning out an experiment and then nailing each step in the protocol. It is very fulfilling. I also enjoy the brainstorming (ブレスト) session with my supervisor about my research. He is very open-minded and patient, always encouraging me to think independently. His feedback has a way of boosting my confidence. I have learnt so much from him.

Yang: It sounds like you have an exceptional supervisor. 

Zheng-san’s experiment table