Tianxiang Hu

Assistant Professor

Tianxiang Hu

Assistant Professor

Academic Appointment(s)

Medical College of Georgia
Department of Biochemistry and Molecular Biology

Bio

Dr. Hu received his PhD degree from Wuhan University in China in 2011. He is currently an assistant professor in the Georgia Cancer Center, and investigates molecular mechanisms of leukemia initiation and progression, aiming at the discovery of novel therapy strategies.

  • (706) 721-8373
  • (706) 721-8354
  • CN 2132

Education

  • Ph.D., Developmental Biology Wuhan University, 2011

Awards & Honors

  • Research excellence award Georgia Cancer Center , 2017

  • 2nd prize of the 1st Research Innovation Competition Wuhan University, 2011

  • Excellent undergraduate thesis award Hubei Province, 2004

Scholarship

Selected Recent Publications

  • Rac1/2 activation promotes FGFR1 driven leukemogenesis in stem cell leukemia/lymphoma syndrome, 2020
    Journal Article, Academic Journal
  • Loss of the BCR-FGFR1 GEF domain suppresses RHOA activation and enhances B-lymphomagenesis in mice, 2019
    Journal Article, Academic Journal
  • DNA methyltransferase 1–mediated CpG methylation of the miR-150-5p promoter contributes to fibroblast growth factor receptor 1– driven leukemogenesis, 2019
    Journal Article, Academic Journal
  • Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome, 2018
    Journal Article, Academic Journal
  • FGFR1 fusion kinase regulation of MYC expression drives development of stem cell leukemia/lymphoma syndrome, 2018
    Journal Article, Academic Journal

Research Interests

Hematologic malignancies associated with FGFR1 abnormalities present in heterogeneous forms, including myeloproliferative neoplasm, acute myeloid leukemia (AML), T- or B-lineage lymphoblastic leukemia/lymphoma, and even mixed phenotype acute leukemia. Also known as Stem Cell Leukemia/Lymphoma syndrome (SCLL), the hallmark of this disease is the presence of chimeric kinases formed as a result of chromosome translocations. By performing bone marrow transduction and transplantation, we have developed syngeneic mouse models of this disease with mouse bone marrow cells in BALB/c mice, and human cell models with CD34+ hematopoietic stem cells in immunocompromised NSG mice, to investigate molecular mechanisms regulating leukemia initiation and progression. Current specific research interests include:

1)    The roles of miRNA in the development of FGFR1 fusion kinase driven SCLL.
miRNAs have pathogenic roles in the development of a variety of leukemias. In an effort to discover the critical roles of miRNAs in the disease progression of SCLL, we carried out a comparison of differentially expressed miRNA in normal counterparts and SCLL cells, we identified the miR-17/92 cluster and miR-339 are direct targets of FGFR1 fusion kinase. Through combined target prediction, luciferase reporter assay and western blotting, we showed that miR-17/92 promoted cell proliferation and survival by targeting CDKN1A and PTEN in B-lymphoma cell lines and primary tumors, while miR-339 promoted development of Stem Cell Leukemia/Lymphoma syndrome via downregulation of the BCL2L11 and BAX pro-apoptotic genes. The report about miR-339 is the first one to demonstrate its oncogenic effect in cancer.

2)    FGFR1 fusion kinase mediated activation of c-Myc and Shp2 oncogenes in SCLL. In an attempt to understand how FGFR1 fusion kinase activate the expression of c-Myc oncogene, we revealed a novel functional model of FGFR1 fusion kinase, in which the full length cytoplasm-restricted chimeric kinases activated cytoplasmic signaling pathways like STAT5, to indirectly activate c-Myc expression, while a truncated form of nucleus-restricted FGFR1, generated by granzyme B cleavage of the chimeric kinases, could bind directly to MYC regulatory regions and activate its expression. In addition, we revealed the disease contribution from fusion partner gene BCR in BCR-FGFR1 driven SCLL, which is the most aggressive subtype of SCLL. With a combination of in vitro proteomic analysis with reverse phase protein array of transformed cell lines and in vivo bone marrow transduction and transplantation experiment in mouse model, we discovered that the BCR serine-threonine kinase activated the Shp2 kinase to promote leukemogenesis. This work rationalizes the necessity in developing precision therapeutics that target the consequences of the fusion partner together with the consistent aspect of the chimeric genes in chromosome translocations related leukemia.

3)    Contribution of Rho family GTPases in FGFR1 fusion kinase driven SCLL.
In Collaboration with Dr. David A. Williams in Harvard Medical School, we investigated the role of Rac1/2, two important members of the Rho GTPases family, in FGFR1 fusion kinase driven SCLL, and revealed that Rac1/2 knockout led to impaired leukemia progression through reduction of leukemia stem/progenitor cell homing and proliferation ability. Moreover, we demonstrated in BCR-FGFR1 fusion mouse model that the GFE domain attenuated leukemia progression through the RhoA/Rock/Pten signaling axis. Loss of the GEF domain or knockdown of RhoA enhanced cell proliferation and invasion potential, resulted in increased leukemogenesis. Regarding the mechanism, loss of the GEF domain suppressed activation of RHOA and PTEN, leading to increased activation of AKT. This can also be the same case for the distinct disease progression caused by the two isoforms p210 and p190 of BCR-ABL1, considering the similar exclusion of the GEF domain in p190.

Department Service

  • Pathways to Success Seminar of Georgia Cancer Center 2020

    Role: Other