Hye Na Kim

All Publications

• Aberrant cell cycle regulation and osteoblastic differentiation in diamond-blackfan anemia (DBA) mesenchymal stem cells Kim, H., Viduya, J., Youm, J., Mark, K., Liu, L., Suchy, F., Nakauchi, H., Shyr, D., Goyal, A., Glader, B., Wu, J. Y., Sakamoto, K. ELSEVIER. 2025: 747-748

  View details for DOI 10.1182/blood-2025-747

  View details for Web of Science ID 001659318900048

• Inflammatory Pathways and the Bone Marrow Microenvironment in Inherited Bone Marrow Failure Syndromes. Stem cells (Dayton, Ohio) Neoman, N., Kim, H. N., Viduya, J., Goyal, A., Liu, Y. L., Sakamoto, K. M. 2025

  Abstract

  Inherited Bone Marrow Failure Syndromes (IBMFS) are a diverse group of genetic disorders characterized by insufficient hematopoietic cell production due to blood stem cell dysfunction. The most common syndromes are Fanconi Anemia, Diamond-Blackfan Anemia, and Shwachman-Diamond Syndrome. These conditions share a theme of chronically producing pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, TGF-β, IFN-I, and IFN-γ. Each of these cytokines can impact the bone marrow microenvironment and drive the pathophysiology of IBMFS. This review aims to provide the latest progress in the field regarding the mechanistic underpinnings of inflammation in these IBMFS, as well as the effect of inflammation on the bone marrow microenvironment. A comprehensive understanding of the inflammation in IBMFS will open new avenues for intervention to restore bone marrow stability and improve patient prognosis. Future research must include targeting these mechanisms to develop novel therapies that can potentially mitigate the effects of chronic inflammation in IBMFS.

  View details for DOI 10.1093/stmcls/sxaf021

  View details for PubMedID 40296192

• Activation of Nemo-like Kinase in Diamond Blackfan Anemia suppresses early erythropoiesis by preventing mitochondrial biogenesis. The Journal of biological chemistry Wilkes, M. C., Shibuya, A., Liu, Y. L., Mark, K., Mercado, J., Saxena, M., Sathianathen, R. S., Kim, H. N., Glader, B., Kenny, P., Sakamoto, K. M. 2024: 107542

  Abstract

  Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown. Here we report that activated NLK suppresses the critical upregulation of mitochondrial biogenesis required in early erythropoiesis. During normal erythropoiesis, mTORC1 facilitates the translational upregulation of Transcription factor A, mitochondrial (TFAM) and Prohibin 2 (PHB2) to increase mitochondrial biogenesis. In our models of DBA, active NLK phosphorylates the regulatory component of mTORC1, thereby suppressing mTORC1 activity and preventing mTORC1-mediated TFAM and PHB2 upregulation and subsequent mitochondrial biogenesis. Improvement of erythropoiesis that accompanies NLK inhibition is negated when TFAM and PHB2 upregulation is prevented. These data demonstrate that a significant contribution of NLK on the pathogenesis of DBA is through loss of mitochondrial biogenesis.

  View details for DOI 10.1016/j.jbc.2024.107542

  View details for PubMedID 38992436