Ep. 283: “Molecular Hematopoiesis” Featuring Dr. Cynthia Dunbar
Dec 3, 2024
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Dr. Cynthia Dunbar, a distinguished investigator at the NIH, dives into the fascinating world of hematopoiesis and aging, using macaques as an innovative model. She discusses groundbreaking research on transplanting iPSC-derived cardiomyocytes, alongside the ethical considerations of using primate models. The unique NIH environment fosters collaboration in stem cell research, enhancing both clinical applications and personalized medicine. Outside the lab, Cindy's musical talents add a delightful twist to her scientific journey.
Dr. Cynthia Dunbar discusses the challenges of using non-human primate models to study aging and hematopoiesis for gene therapies.
The podcast emphasizes advances in hematopoietic gene therapy, particularly in utilizing gene editing technologies for treating conditions like sickle cell disease.
Dunbar highlights the ethical implications of using primate models in research, necessitating a careful balance between scientific advancement and humane treatment.
Deep dives
Dr. Cynthia Dunbar's Research Focus
Dr. Cynthia Dunbar is engaged in significant research on hematopoiesis gene therapies, utilizing non-human primate models to deepen the understanding of blood cell formation and function. Her lab concentrates on the complex processes involved in aging and the effects of somatic mutations on hematopoietic stem cells. These investigations aim to delineate the risks associated with gene therapies that may lead to complications such as clonal hematopoiesis and various malignancies. By employing advanced techniques like genetic barcoding and single-cell gene expression analysis, her research endeavors to track stem cells and their progeny, with implications for both health and disease.
Advancements in Hematopoietic Gene Therapy
The podcast highlights the rapid progress in hematopoietic gene therapy, particularly in addressing diseases like sickle cell and thalassemia. The field has made remarkable strides with the advent of gene editing technologies, which offer potential curative options for patients. However, challenges remain, especially concerning insertional mutagenesis and the longevity of treatment benefits. Dunbar emphasizes the need to balance therapeutic efficacy with ensuring the long-term safety of these gene modification approaches.
Impacts of Aging on Stem Cell Function
A significant area of focus within Dunbar's research is the understanding of how aging affects hematopoietic stem cell function. As individuals age, their marrow undergoes changes that hinder the production of immune cells and increase susceptibility to malignancies. Investigating the molecular pathways that lead to these age-related alterations is crucial for developing effective therapies. By studying non-human primates, researchers can better model human aging processes and their effects on blood cell production.
Neural Crest Origin and Regeneration
During the discussion, a fascinating point raised involves the lineage origins of different cell types, specifically concerning the neural crest's role in regeneration. The podcast mentions ongoing research that seeks to elucidate how cells originating from the neural crest could contribute to regenerative processes in other tissues. The implications of understanding this lineage are profound, as it may provide insights into enhancing regenerative medicine and therapeutic strategies. This area of study opens new avenues for exploring cellular plasticity and developmental biology.
Clinical Applications and Challenges of CAR T-Cells
The podcast delves into the clinical applications of CAR T-cell therapies, particularly in treating blood cancers. These therapies leverage the body’s immune response but also introduce challenges, such as potential toxicity and the need for personalized treatment plans. Dunbar discusses how understanding the biology of hematopoietic stem cells can improve the effectiveness and safety of CAR T-cell therapies. The conversation highlights the importance of optimizing these therapies to sustain long-term remission in patients suffering from hematologic malignancies.
Ethical Considerations in Non-Human Primate Research
A significant aspect discussed relates to the ethical considerations surrounding the use of non-human primate models in biomedical research. Dunbar emphasizes the importance of maintaining rigorous ethical standards given the close genetic and physiological similarities between these animals and humans. The unique advantages provided by primate models for studying complex biological processes, such as hematopoiesis, are balanced with a moral obligation to ensure the humane treatment of these subjects. This balance requires researchers to justify the necessity of such models for answering difficult scientific questions while minimizing animal suffering.
Dr. Cynthia “Cindy” Dunbar is National Institutes of Health (NIH) Distinguished Investigator and Chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute of the NIH. She talks about using macaques to study hematopoiesis and aging, and the challenges and considerations for using these models. She also discusses her collaborative study transplanting iPSC-derived cardiomyocytes into rhesus macaques, as well as the NIH’s unique research environment and her musical talents outside of the lab.
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