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cover of episode #290 ‒ Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

#290 ‒ Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

2024/2/19
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Alex Aravanis: 本期节目讨论了液体活检和表观遗传学两个相互关联的主题。首先,他追溯了基因组测序和肿瘤测序的发展历程,为详细探讨液体活检作为癌症早期检测方法奠定了基础。讨论内容涵盖了细胞游离DNA、DNA甲基化、灵敏度、特异性以及与液体活检相关的预测值等关键概念。随后,Alex Aravanis探讨了DNA甲基化与衰老生物学之间的复杂相互作用,并探讨了利用细胞重编程逆转衰老过程中发生的表观遗传变化的可能性。他还介绍了他在将工程技术应用于医学问题上的经验,以及如何利用这些技术来解决生物学中的重要问题。他详细阐述了下一代测序技术的发展,以及如何利用这些技术来降低测序成本,并将其应用于临床实践。他还讨论了液体活检技术的三个应用方向:筛查、治疗选择和监测。 Peter Attia: Peter Attia与Alex Aravanis讨论了液体活检和表观遗传学在癌症早期检测和衰老研究中的作用。Peter Attia详细询问了液体活检技术的原理、发展历程以及在临床实践中的应用。他特别关注了GRAIL公司开发的多癌早期筛查试验Galleri,并探讨了该试验的灵敏度、特异性、阳性预测值和阴性预测值。此外,他还与Alex Aravanis讨论了表观遗传学在衰老中的作用,以及如何利用细胞游离DNA甲基化模式来识别癌症的组织来源。他们还探讨了细胞和表观遗传重编程以及衰老研究领域的其它令人兴奋的工作。Peter Attia还提出了关于早期癌症检测方法是否能改善整体生存率以及如何平衡灵敏度和特异性的问题。

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Alex Aravanis, CEO and co-founder of Moonwalk Biosciences, discusses his journey from electrical engineering to medicine. His PhD research at Stanford, under the mentorship of Dick Chen, focused on applying engineering principles to understand the brain's communication processes. This led to groundbreaking discoveries about synaptic vesicle function, published in Nature.
  • Quantum unit of communication in the brain is the synaptic vesicle
  • Developed a method to study how information is transmitted between cells
  • Published in Nature

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Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging.

We discuss:

  • Alex’s background in applying engineering to problems in medicine [3:15];
  • A primer on human genetics, and the history and current landscape of DNA sequencing [11:00];
  • The advent and evolution of liquid biopsies for early detection of cancer [23:15];
  • The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15];
  • The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00];
  • Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00];
  • DNA methylation explained [58:15];
  • Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45];
  • The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00];
  • The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00];
  • Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45];
  • The role of epigenetics in aging [1:39:30];
  • How cell-free DNA methylation patterns can help identify a cancer’s tissue of origin [1:45:30];
  • Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and
  • More.

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