Brad L. Jakubison
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Brad L. Jakubison has a total of 7 co-authors. Here are the top co-authors by number of shared publications:
Holly M. Morris
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute (NCI) – Frederick, NIH, Frederick, Maryland, USA
1 shared publication- Jonathan R. Keller
National Cancer Institute - Frederick
1 shared publication Kimberly D. Klarmann
Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
1 shared publication- Kristbjorn Orri Gudmundsson
Mouse Cancer Genetics Program, Center For Cancer Research, National Cancer Insitute-Frederick, NIH, Frederick, MD 21702, USA
1 shared publication - Lei Sun
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute (NCI) – Frederick, NIH, Frederick, Maryland, USA
1 shared publication - Shweta Singh
Mouse Cancer Genetics Program, Center for Cancer Research, NCI, Frederick, MD 21702, USA
1 shared publication
Latest Publications
- Open Access
- 1 July 2022
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 132 (13)
ID2 and HIF-1α collaborate to protect quiescent hematopoietic stem cells from activation, differentiation, and exhaustion
Defining mechanism(s) that maintain tissue stem quiescence is important for improving tissue regeneration, cell therapies, aging, and cancer. We report here that genetic ablation of Id2 in adult hematopoietic stem cells (HSCs) promotes increased HSC activation and differentiation, which results in HSC exhaustion and bone marrow failure over time. Id2Δ/Δ HSCs showed increased cycling, ROS production, mitochondrial activation, ATP production, and DNA damage compared with Id2+/+ HSCs, supporting the conclusion that Id2Δ/Δ HSCs are less quiescent. Mechanistically, HIF-1α expression was decreased in Id2Δ/Δ HSCs, and stabilization of HIF-1α in Id2Δ/Δ HSCs restored HSC quiescence and rescued HSC exhaustion. Inhibitor of DNA binding 2 (ID2) promoted HIF-1α expression by binding to the von Hippel-Lindau (VHL) protein and interfering with proteasomal degradation of HIF-1α. HIF-1α promoted Id2 expression and enforced a positive feedback loop between ID2 and HIF-1α to maintain HSC quiescence. Thus, sustained ID2 expression could protect HSCs during stress and improve HSC expansion for gene editing and cell therapies.
- 1 July 2022
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 132 (13)
Open AccessID2 and HIF-1α collaborate to protect quiescent hematopoietic stem cells from activation, differentiation, and exhaustion
Defining mechanism(s) that maintain tissue stem quiescence is important for improving tissue regeneration, cell therapies, aging, and cancer. We report here that genetic ablation of Id2 in adult hematopoietic stem cells (HSCs) promotes increased HSC activation and differentiation, which results in HSC exhaustion and bone marrow failure over time. Id2Δ/Δ HSCs showed increased cycling, ROS production, mitochondrial activation, ATP production, and DNA damage compared with Id2+/+ HSCs, supporting the conclusion that Id2Δ/Δ HSCs are less quiescent. Mechanistically, HIF-1α expression was decreased in Id2Δ/Δ HSCs, and stabilization of HIF-1α in Id2Δ/Δ HSCs restored HSC quiescence and rescued HSC exhaustion. Inhibitor of DNA binding 2 (ID2) promoted HIF-1α expression by binding to the von Hippel-Lindau (VHL) protein and interfering with proteasomal degradation of HIF-1α. HIF-1α promoted Id2 expression and enforced a positive feedback loop between ID2 and HIF-1α to maintain HSC quiescence. Thus, sustained ID2 expression could protect HSCs during stress and improve HSC expansion for gene editing and cell therapies.