Latexin signaling in hematopoietic regeneration and leukemia development
We have discovered novel role of latexin gene in the regulation of normal and malignant hematopoiesis. We have found that 1) Inhibition of latexin can expand normal stem cell, which will benefit cancer patients who need sufficient number of stem cells for transplantation. 2) Inhibition of latexin can mitigate radiation and chemotherapy-induced blood cell suppression, thus benefit cancer patients. 3) Inhibition of latexin in bone marrow niche suppresses leukemia stem cell and leukemia development. 4) Drug screening identified several novel latexin inhibitors, which hold the promise for novel therapeutic targets.
Inflammaging in the regulation of HSC and immune function
Aging is associated with inflammation. Acute infection or chronic systemic inflammation can remarkably change the hematopoietic and immune system, including emergency granulopoiesis, lymphoid suppression, and HSC functional impairment. We have identified the important role of inflammatory cytokine S100A8/A9 in the regulation of HSC and immune function in response to acute COVID19 infection.
Aging niche in clonal evolution of leukemia stem cell and leukemia development.
Aging is the biggest risk factor for cancer development. Clonal hematopoiesis has recently been identified as an aging hallmark and contributes to age-related leukemia development and cardiovascular diseases. Several genetic mutations are associated with clonal hematopoiesis. Asxl1 is one of the top 5 genes, but its mechanism in clonal evolution and leukemogenesis remain largely unknown. We have found that aging niche contributes to the clonal expansion of Asxl1 mutant HSC, and the age-associated extrinsic changes may underlie the increased risk for myelodysplastic syndrome and leukemia development in the elderly.
Sex dimorphism in the regulation of normal and malignant hematopoiesis
Sex dimorphism exists in hematopoietic stem and progenitor cells, but also the development of hematopoietic lineages, resulting in sexual dimorphisms in normal hematopoiesis. Moreover, males are at greater risk and have worse prognosis for most of hematologic malignancies compared to females. My lab has identified that male niche has a better support for HSC regeneration compared to female niche. The single niche cell sequencing suggests that several cellular components, including mesenchymal stem cells (MSC), fibroblasts, adipocytes and megakaryocytes, the most significant sex difference. We further identified that several cytokines in male niche provides better support for male HSC regeneration. We are currently studying the mechanism underlying differential expression of these cytokines in male/female niche.
Hematopoiesis is a continuous and well-regulated process requiring both the capacity for self-renewal and the potential for differentiation of hematopoietic (or blood-forming) stem cell (HSC). Cell-intrinsic and niche/system-extrinsic factors coordinately work on HSC regulation and maintain hemostatic and malignant hematopoiesis. My research is focused on the molecular mechanisms regulating HSC and immune aging, stress response and transformation. Another research focus is the sex dimorphism in normal and malignant hematopoiesis. My long-term goal is to apply the findings to develop gender specific precision medicine and therapy for aging-related degenerative diseases and hematological malignancies
- R01 HL124015, Liang (PI), 09/01/21 – 7/31/25, Latexin function in the maintenance and regeneration of the hematopoietic system
- R01 DK130478, Liang (Contact PI), Huang (MPI), 09/01/21 – 06/31/24, Mechanism of the short- and long-term effects of COVID-19-induced Alarmins on hematopoietic stem and progenitor cells
- R21HL166178, Liang (Co-Investigator), Tong (Contact PI), 01/01/23-12/31/24, Precise in vivo gene editing of HSPC for the treatment of genetic hematologic diseases
Education & Training
MD, Beijing Medical University, Beijing, China
PhD, Hematopoiesis, University of Kentucky, Lexington, KY
Hematopoiesis, University of Kentucky
Liang Y, Van Zant G, Szilvassy SJ. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005; 106(4): 1479-1487.
Liang Y, Jansen M, Aronow B, Geiger H, Van Zant G. The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice. Nature Genetics. 2007; 39(2): 178-188
You Y, Wen R, Pathak R, Li A, Li W, St Clair D, Hauer-Jensen M, Zhou D, Liang Y. Latexin sensitizes leukemogenic cells to gamma-irradiation-induced cell-cycle arrest and cell death through Rps3 pathway. Cell Death & Disease. 2014; 23;5:e1493.
Liu Y, Zhang C, Li Z, Wang C, Jia J, Gao T, Hildebrandt G, Zhou D, Bondada S, Ji P, St Clair D, Liu J, Zhan C, Geiger H, Wang S, Liang Y. “Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice.” Stem Cell Reports. 2017; 8, 4: 991-1004
Zhang C, Yvonne N Fondufe-Mittendorf, Chi Wang, Jing Chen, Qiang Cheng, Daohong Zhou, Yi Zheng, Hartmut Geiger, Liang Y. Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance. Haematologica. 2020 Mar; 105(3):573-584. (Editorial Highlight)
Cui X, Zhao X, Liang Y. Sex Differences in Normal and Malignant Hematopoiesis. Blood Science. 2022 Oct;4(4):185-191
Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong and Ying Liang. Latexin regulates hematopoiesis in a sex-dependent manner by differential expression of sex chromosome-specific microRNA 98-3p and thrombospondin 1. Cell Reports, 2023 (In press)
Xiaojing Cui, PhD, Postdoctoral fellow
Yanyan De, PhD, Postdoctoral fellow