About

Jonathan Klein is a professor in the Department of Pediatrics at Stanford University. His research focuses on pediatric health, and he is involved in the academic community within the Stanford Program in Human Biology. As a faculty member, he contributes to the education and training of students in the field of human biology and pediatrics, supporting the interdepartmental undergraduate program and engaging in research related to child health and development.

Research topics

• Biology
• Cancer research
• Medicine
• Genetics
• Computational biology
• Cell biology
• Internal medicine
• Pathology
• Endocrinology

Selected publications

• Death-seq identifies regulators of cell death and senolytic therapies

  Cell Metabolism · 2023 · 32 citations

  • Medicine
  • Cancer research
  • Biology
  PublisherOA PDFDOI

• Death-seq identifies regulators of cell death and senolytic therapies

  bioRxiv (Cold Spring Harbor Laboratory) · 2022 · 7 citations

  • Biology
  • Cancer research
  • Computational biology

  SUMMARY Selectively ablating senescent cells (“senolysis”) is an evolving therapeutic approach for age-related diseases. Current senolytics are limited to local administration by potency and side effects. While genetic screens could identify senolytics, current screens are underpowered for identifying genes that regulate cell death due to limitations in screen methodology. Here, we establish Death-seq, a positive selection CRISPR screen optimized to identify enhancers and mechanisms of cell death. Our screens identified synergistic enhancers of cell death induced by the known senolytic ABT-263, a BH3 mimetic. SMAC mimetics, enhancers in our screens, synergize with ABT-199, another BH3 mimetic that is not senolytic alone, clearing senescent cells in models of age-related disease while sparing human platelets, avoiding the thrombocytopenia associated with ABT-263. Death-seq enables the systematic screening of cell death pathways to uncover molecular mechanisms of regulated cell death subroutines and identify drug targets for diverse pathological states such as senescence, cancer, and neurodegeneration.

  PublisherOA PDFDOI

• Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling

  Cell Metabolism · 2022 · 70 citations

  • Biology
  • Cell biology
  • Internal medicine
  PublisherOA PDFDOI

• Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-01-04 · 5 citations

  preprintOpen access

  Summary Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.

  PublisherOA PDFDOI

• Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

  Science · 2019-11-07 · 76 citations

  articleOpen access

  Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3' untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

  PublisherOA PDFDOI

• Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence

  Proceedings of the National Academy of Sciences · 2017-10-09 · 94 citations

  articleOpen access

  Significance This work addresses a fundamental mechanism for the translational control of a master regulator of myogenic differentiation, MyoD, by the RNA binding protein Staufen1. We show that muscle stem cells express the MyoD transcript in the quiescent state in vivo but block its translation through direct repression by Staufen1. Loss of this translational repression leads to MyoD translation and cell cycle entry, highlighting a novel role for MyoD in regulating the exit from quiescence. This mechanism of direct translational repression enables the cells to exist poised for activation and cell cycle entry. These data provide insight in the translational control of muscle stem cell quiescence.

  PublisherOA PDFDOI

• Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

  Cell · 2017-03-01 · 1417 citations

  letterOpen access
  PublisherOA PDFDOI

Frequent coauthors

• Thomas A. Rando

  VA Palo Alto Health Care System

  12 shared

• Léo Machado

  Inserm

  6 shared

• Antoine de Morrée

  Stanford University

  4 shared

• Marco Quarta

  Sea Lane Biotechnologies (United States)

  4 shared

• Jayesh S. Salvi

  Stanford University

  3 shared

• Armon Goshayeshi

  Stanford University

  2 shared

• Daniel I. Benjamin

  Stanford University

  2 shared

• Soochi Kim

  Stanford University

  2 shared