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RESEARCH FOCUS AREAS:
- Hematopoiesis
- Stem cell self-renewal
- Bone marrow microenvironment
- Cell signaling
RESEARCH SUMMARY:
Our laboratory is committed to understanding how the molecular signals that emerge from the bone marrow (BM) micro-environmental niche regulate normal hematopoiesis and how deregulation of such signaling is involved in the pathogenesis of hematopoietic disorders. Specifically, we have identified: 1) factors from the normal BM niche which regulate self-renewal of hematopoietic stem cells (HSCs). We want to use such factors to stimulate the expansion of HSCs in in vitro culture for the purpose of improving the success of transplantation therapy and to induce hematopoietic regeneration in conditions of BM failure; 2) factors and related signals from diseased BM which are causally involved in disease initiation, progression and/or drug-resistance. We intend to use such information to develop novel medications for the purpose of preventing the progression of pre- leukemia to leukemia, and to develop targeted therapies to combat drug-resistant cases of leukemia. We use unbiased systematic techniques such as RNA sequencing (from RT-PCR) and shRNA/Crispr screening assays in our factor identification process. We then use both in vitro culture assays and in vivo animal models to functionally verify these factors. Finally, we always seek the goal of translating our discoveries by further evaluating our findings in primary patient samples and xenograft models.
EDUCATION:
- MD, Lanzhou Medical College, China
- PhD, Shanghai Institute of Hematology, Shanghai, China
- Postdoctoral fellowship, Stowers Institute for Medical Research
SELECT PUBLICATIONS:
- Role of TET dioxygenases in the regulation of both normal and pathological hematopoiesis Joshi, K; Zhang, L; Breslin, S J P; Kini, AR; Zhang, J Journal of Experimental & Clinical Cancer Research 2022 Oct 7;41(1):294. doi: 10.1186/s13046-022-02496-x. PMID: 36203205; PMCID: PMC9540719
- The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma Sellin, M; Berg, S; Hagen, P; Zhang, J Translational Oncology 2022 Aug;22:101448. doi: 10.1016/j.tranon.2022.101448. Epub 2022 Jun 1. PMID: 35660848; PMCID: PMC9166471
- Molecular mechanisms by which splice modulator GEX1A inhibits leukaemia development and progression Sellin, M; Mack, R; Rhodes, MC; Zhang, L; Berg, S; Joshi, K; Liu, S; Wei, W; Breslin, S J P; Larsen, P; Taylor, RE; Zhang, J British Journal of Cancer 2022 Jul;127(2):223-236. doi: 10.1038/s41416-022-01796-5. Epub 2022 Apr 14. PMID: 35422078; PMCID: PMC9296642
- Mechanisms that regulate the activities of TET proteins Joshi, K; Liu, S; Breslin, S J P; Zhang, J Cellular and Molecular Life Sciences 2022 Jun 15;79(7):363. doi: 10.1007/s00018-022-04396-x. PMID: 35705880
- Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice Zhang, L; Luo, H; Ni, HM; Liu, S; Xing, H; Zhang, J; Sellin, M; Breslin, S J P; Wei, W; Denning, MF; Small, W Jr; Ding, WX; Huang, S; Zhang, J Stem Cell Reports 2022 Jun 14;17(6):1428-1441. doi: 10.1016/j.stemcr.2022.04.009. Epub 2022 May 12. PMID: 35561683; PMCID: PMC9213819
- The role of TBK1 in cancer pathogenesis and anticancer immunity Runde, AP; Mack, R; Breslin, S J P; Zhang J Journal of Experimental Clinical Cancer Research 2022 Apr 9;41(1):135. doi:10.1186/s13046-022-02352-y. PMID: 35395857; PMCID: PMC8994244
- The fetal-to-adult hematopoietic stem cell transition and its role in childhood hematopoietic malignancies Mack, R; Zhang, L; Breslin, SJ P; Zhang, J Stem Cell Reviews and Reports 2021 Dec;17(6):2059-2080. doi: 10.1007/s12015-021-10230-x. Epub 2021 Aug 23. PMID: 34424480; PMCID: PMC9059172
- Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice Sheng, Y; Ma, R; Yu, C; Wu, Q; Zhang, S; Paulsen, K; Zhang, J; Ni, H; Huang, Y; Zheng, Y; Qian, Z Blood 2021 Feb 4;137(5):610-623. doi: 10.1182/blood.2019004688. PMID: 33538795; PMCID: PMC8215193
- Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches Zhang, L; Mack, R; Breslin, P; Zhang, J Journal of Hematology & Oncology 2020 Nov 23;13(1):157. doi: 10.1186/s13045-020-00994-z. PMID: 33228751; PMCID: PMC7686726
- Tumor microenvironment-derived R-spondins enhance antitumor immunity to suppress tumor growth and sensitize for immune checkpoint blockade therapy Tang, Y; Xu, Q; Hu, L; Yan, X; Feng, X; Yokota, A; Wang, W; Zhan, D; Krishnamurthy, D; Ochayon, DE; Wen, L; Huo, L; Zeng, H; Luo, Y; Huang, LF; Wunderlich, M; Zhang, J; Vivier, E; Zhou, J; Waggoner, SN; Huang, G Cancer Discovery 2021 Dec 1;11(12):3142-3157. doi: 10.1158/2159-8290.CD-20-0833. PMID: 34193438; PMCID: PMC8716674
Publications:
Jiwang Zhang Publications
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