研究员，PI，博士研究生导师

Email: sunjianlong@muhn.edu.cn

1. 教育经历

博士，美国得克萨斯大学健康科学中心圣安东尼奥分校，2004-2009

学士，复旦大学，1995-1999

2. 工作经历

研究员，海南医科大学                                                      2026-至今

研究员、助理教授，上海科技大学                                            2017-2026

博士后，哈佛大学波士顿儿童医院                                            2010-2017

博士后，美国得克萨斯大学健康科学中心圣安东尼奥分校                        2009-2010  

3.课题组简介

    孙建龙课题组长期致力于造血调控及白血病发生发展的细胞与分子机制研究。课题组综合利用小鼠模型、谱系示踪、克隆分析、原代细胞培养、多组学分析及流式细胞术等研究手段，系统解析造血干 / 祖细胞在稳态、炎症、衰老及肿瘤等生理与病理状态下的命运调控机制。课题组已取得系列重要研究进展：揭示衰老背景下造血干 / 祖细胞的克隆演化规律；阐明化疗应激条件下造血干细胞的细胞命运动态重塑机制；解析炎症因子调控造血祖细胞髓系 - 淋系分化命运转换的分子基础；阐释急性髓系白血病进程中正常造血干细胞向白血病干细胞转化的调控机理。相关成果发表于 Developmental Cell、eLife、Cell Reports等高水平学术期刊。课题组研究工作先后得到国家高层次人才项目、科技部重点研发计划、国家自然科学基金面上项目等多项课题资助。

4.研究方向

在已有研究基础上，课题组将重点围绕以下四个方向开展深入探索：

衰老对造血干细胞血液再生功能的影响和应对策略

    血液系统再生能力下降是老年肿瘤患者不耐受高剂量化疗的关键原因。促进衰老个体化疗后血细胞快速恢复，有望显著提高老年患者对高剂量化疗的耐受性。本研究以小鼠模型为载体，运用谱系示踪、克隆分析和多组学技术，揭示衰老造血干细胞血细胞再生的分化路径与动力学规律，解析再生功能受损的分子基础，并探寻化疗环境下恢复衰老造血干细胞功能的干预手段。

衰老过程中造血系统淋系分化障碍的分子机制和逆转策略

    获得性免疫系统功能随年龄增长显著衰退，衰老伴随的慢性炎症被认为是诱发淋系分化障碍的关键因素。我们前期研究发现，短期炎症因子刺激可促进多能造血祖细胞向淋系分化，而持续长期刺激则显著抑制其淋系分化潜能。本研究方向将系统比较上述两种刺激条件下多能造血祖细胞的谱系分化差异，解析背后的分子机制，探索在慢性炎症微环境中恢复多能造血祖细胞淋系分化能力的干预策略。同时，我们将依托多能祖细胞与淋系祖细胞特异性谱系示踪体系，阐释应激、炎症及衰老状态下淋系细胞分化与再生的动力学特征及其调控机理。

克隆造血的细胞和分子机制及逆转策略

    克隆造血是衰老进程中血液系统普遍存在的生物学现象。多种白血病相关基因突变可在白血病发病之前即于外周血和骨髓中发生异常克隆扩增，显著升高白血病的发病风险。在恶性转化发生之前靶向管控突变造血细胞，是白血病预防的重要思路。与此同时，克隆造血与多类实体器官的慢性炎症及肿瘤发生密切相关；如何遏制异常克隆的扩增，进而预防、延缓多种衰老相关慢性疾病，是衰老生物学领域的重要研究方向。本研究将结合谱系示踪、克隆分析与多组学技术，系统探究常见克隆造血相关突变对造血干 / 祖细胞自我更新、多谱系分化以及成熟血细胞免疫功能的影响，阐明其背后的分子调控机制，探索靶向抑制克隆扩增的干预策略，以期延缓衰老、维持机体健康稳态。

难治型急性髓系白血病的分子机制研究

    成人急性髓系白血病（AML）发病率随年龄增长显著升高，其 5 年总生存率不足 25%；其中伴骨髓增生异常相关改变的 AML 预后更差。本研究将整合组学数据挖掘与白血病基因工程小鼠模型，解析难治性 AML 对关键基因及信号通路的依赖特征，系统阐释正常造血干细胞向白血病干细胞恶性转化的动态过程与调控机理，发掘新型靶向及免疫治疗靶点，并依托患者来源异种移植（PDX）模型开展临床前疗效评价与机制研究。

5. 发表论文

Zhang Z, Jin B, You C, Li Y, Lin L, Sun J*. (2026) Hematopoietic stem cells activate a latent differentiation pathway to facilitate hematopoietic recovery immediately after 5-fluorouracil-induced myeloablation. Developmental Cell. 2026 Mar 2:S1534-5807(26)00043-2

Tang L, Lu M, Du Y, Sun J*. (2025) Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9. Cancer Gene Therapy. 32(4):475-485. (* corresponding author)

Liu L, Wu P, Wei Y, Lu M, Ge H, Wang P, Sun J, Horng T, Liu X, Shen X, Sun L, Xi Y. (2025) TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages. Cell Reports. 44(2):115220.

You C, Zhang Z, Lin L, Sun J*. (2025) Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesis, eLife, https://doi.org/10.7554/eLife.104537.1 (* corresponding author)

Xia J, Lan L, You C, Tang L, Chen T, Yang Y, Lin L, Sun J*. (2024) Interleukin-1β modulates lymphoid differentiation of Flt3-positive multipotent progenitors after transplantation. Cell Reports. 43(11):114890. (* corresponding author)

Zhang Z, Sun J*. (2023) The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases.

Advances in Experimental Medicine and Biology. 1442:65-83. (* corresponding author)

Li F, Sun J*. (2023) Differentiation Kinetics of Hematopoietic Stem and Progenitor Cells In Vivo Are Not Affected by β-Glucan Treatment in Trained Immunity. Inflammation. 46(2):718-729. (* corresponding author)

Liu B, Jing Z, Zhang X, Chen Y, Mao S, Kaundal R, Zou Y, Wei G, Zang Y, Wang X, Lin W, Di M, Sun Y, Chen Q, Li Y, Xia J, Sun J, Lin CP, Huang X, Chi T. (2022) Large-scale multiplexed mosaic CRISPR perturbation in the whole organism. Cell.185(16):3008-3024.e16.

Lu Y, Deng R, You H, Xu Y, Antos C, Sun J, Klein OD, Lu P. Asymmetric Stratification-Induced Polarity Loss and Coordinated Individual Cell Movements Drive Directional Migration of Vertebrate Epithelium. Cell Reports. 2020 Oct 13;33(2):108246.

Li Y, Chen Y, Mao S, Kaundal R, Jing Z, Chen Q, Wang X, Xia J, Liu D, Sun J, Wang H, Chi T. In situ conversion of defective Treg into SuperTreg cells to treat advanced IPEX-like disorders in mice. Nature Communications. 2020 Jun 3;11(1):2781.

Sun J. CRISPR-Mediated Recording of Mouse Development. CRISPR J. 2018 Oct;1:314-316

Rodriguez-Fraticelli AE, Wolock SL, Weinreb CS, Panero R, Patel SH, Jankovic M, Sun J, Calogero RA, Klein AM, Camargo FD (2018) Clonal analysis of lineage fate in native haematopoiesis. Nature. 2018 Jan 11;553(7687):212-216

Sun J, Ramos A, Chapman B, Johnnidis J, Le L, Ho Y, Klein A, Hofmann O, Camargo FD (2014) Clonal dynamics of native hematopoiesis. Nature 514(7522):322-7

Mohseni M, Sun J, Lau A, Curtis S, Goldsmith J, Fox VL, Wei C, Frazier M, Samson O, Wong KK, Kim C, Camargo FD (2014) A genetic screen identifies an LKB1/PAR1 signaling axis controlling the Hippo/YAP pathway.  Nat Cell Biol 16(1):108-17

Sun J, Pan H, Lei C, Yuan B, Nair SJ, April C, Parameswaran B, Klotzle B, Fan JB, Ruan J, Li R. (2011) Genetic and genomic analyses of RNA polymerase II-pausing factor in regulation of mammalian transcription and cell growth. J Biol Chem 286(42):36248-57

Sun J, Li R (2010) Human Negative Elongation Factor (NELF) activates transcription and regulates alternative transcription initiation. J Biol Chem 285(9):6443-6452

Amleh A, Sreejith N, Sun J, Sutherland A, Hasty P, Li R (2009) Cofactor of BRCA1 (COBRA1) controls embryogenesis and pluripotency of mouse embryonic stem cells. Plos One 4(4):e5034

Sun J, Watkins G, Blair AL, Moskaluk C, Ghosh S, Jiang WG, Li R. (2008) Deregulation of cofactor of BRCA1 expression in breast cancer cells. J Cell Biochem 103(6):1798-1807

Sun J, Blair AL, Aiyar SE, Li R. (2007) Cofactor of BRCA1 modulates androgen-dependent transcription and alternative splicing. J Steroid Biochem Mol Biol 107(3-5):131-139

Lu Y-Z, Ameleh A, Sun J, McCullough SD, Baer R, Ren D-M, Li R, Hu Y-F. (2007) Proteasome-mediated degradation of BRCA1 and BARD1 during steroidogensis in human ovarian granulosa cells. Mol Endocrinology 21:651-663

Aiyar SE, Sun J, Li R. (2005) BRCA1: A locus-specific liaison in gene expression and genetic integrity. J Cell Biochem 94: 1103-1111

Aiyar SE, Sun J, Blair AL, Moskaluk CA, Lv Y, Ye Q-N, Yamaguchi Y, Mukherjee A, Ren D- M, Handa H, Li R. (2004) Attenuation of estrogen receptor a-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes & Dev 18:2134-2146.