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Thank you to the Alliance for Regenerative Medicine for welcoming me to the Women’s Executive Forum! I’m thrilled to join this community dedicated…
Thank you to the Alliance for Regenerative Medicine for welcoming me to the Women’s Executive Forum! I’m thrilled to join this community dedicated…
Posted by Laura Lande-Diner
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We announced our Half Year 2024 results today. PureTech Health continues to make excellent progress across our business. With an exciting pipeline of…
We announced our Half Year 2024 results today. PureTech Health continues to make excellent progress across our business. With an exciting pipeline of…
Liked by Laura Lande-Diner
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Eugene Bell's 1981 Science paper demonstrated engraftment of tissue engineered skin in a rat, marking a milestone in a new field. So honored to be…
Eugene Bell's 1981 Science paper demonstrated engraftment of tissue engineered skin in a rat, marking a milestone in a new field. So honored to be…
Liked by Laura Lande-Diner
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Publications
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Distinguishing between stochasticity and determinism: Examples from cell cycle duration variability.
Bioessays.
We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we…
We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we discuss the sources of such variability and the possibility that the underlying deterministic process is due to the circadian clock. Finally, we discuss the "kicked cell cycle" model and its implication on the study of the cell cycle in healthy and cancerous tissues.
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Single cell analysis of circadian dynamics in tissue explants.
Mol Biol Cell.
Tracking molecular dynamics in single cells in-vivo is instrumental to our understanding of how cells act and interact in tissues. Current tissue imaging approaches have focused on short term observation and typically non-endogenous or implanted samples. Here, we developed an experimental and computational setup that allows for single cell tracking of a transcriptional reporter over a period of more than a week, in the context of an intact tissue. We focused on the peripheral circadian clock as…
Tracking molecular dynamics in single cells in-vivo is instrumental to our understanding of how cells act and interact in tissues. Current tissue imaging approaches have focused on short term observation and typically non-endogenous or implanted samples. Here, we developed an experimental and computational setup that allows for single cell tracking of a transcriptional reporter over a period of more than a week, in the context of an intact tissue. We focused on the peripheral circadian clock as a model system and measured the circadian signaling of hundreds of cells from two tissues. The circadian clock is an autonomous oscillator whose behavior is well described in isolated cells, but in situ analysis of circadian signaling in single cells of peripheral tissues is as yet uncharacterized. Our approach allowed us to investigate the oscillatory properties of individual clocks, to determine how these properties are maintained among different cells, and to assess how they compare to the population rhythm. These experiments, using a wide field microscope, a previously generated reporter mouse, and custom software to track cells over days, suggest how many signaling pathways might be quantitatively characterized in explant models.
© 2015 by The American Society for Cell Biology.Other authorsSee publication -
A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery.
Proc Natl Acad Sci U S A
Circadian clocks in mammals are built on a negative feedback loop in which the heterodimeric transcription factor circadian locomotor output cycles kaput (CLOCK)-brain, muscle Arnt-like 1 (BMAL1) drives the expression of its own inhibitors, the PERIOD and CRYPTOCHROME proteins. Reactivation of CLOCK-BMAL1 occurs at a specific time several hours after PERIOD and CRYPTOCHROME protein turnover, but the mechanism underlying this process is unknown. We found that mouse BMAL1 complexes include…
Circadian clocks in mammals are built on a negative feedback loop in which the heterodimeric transcription factor circadian locomotor output cycles kaput (CLOCK)-brain, muscle Arnt-like 1 (BMAL1) drives the expression of its own inhibitors, the PERIOD and CRYPTOCHROME proteins. Reactivation of CLOCK-BMAL1 occurs at a specific time several hours after PERIOD and CRYPTOCHROME protein turnover, but the mechanism underlying this process is unknown. We found that mouse BMAL1 complexes include TRAP150 (thyroid hormone receptor-associated protein-150; also known as THRAP3). TRAP150 is a selective coactivator for CLOCK-BMAL1, which oscillates under CLOCK-BMAL1 transcriptional control. TRAP150 promotes CLOCK-BMAL1 binding to target genes and links CLOCK-BMAL1 to the transcriptional machinery at target-gene promoters. Depletion of TRAP150 caused low-amplitude, long-period rhythms, identifying it as a positive clock element. The activity of TRAP150 defines a positive feedback loop within the clock and provides a potential mechanism for timing the reactivation of circadian transcription.
Other authorsSee publication -
The critical discussion group: fostering personal and scientific growth.
Mol Cell
As scientists, we greatly benefit from discussing our work with our peers. Informal, unstructured interactions often yield highly creative feedback. With this in mind, we created a group that fosters discussion of its members' work. The group engages us in new research fields and ways of thinking, and provides us with an opportunity for co-mentoring. Three key components were essential for making this group work: the emphasis on non-hierarchical debate; the diversity of the group members; and…
As scientists, we greatly benefit from discussing our work with our peers. Informal, unstructured interactions often yield highly creative feedback. With this in mind, we created a group that fosters discussion of its members' work. The group engages us in new research fields and ways of thinking, and provides us with an opportunity for co-mentoring. Three key components were essential for making this group work: the emphasis on non-hierarchical debate; the diversity of the group members; and the mutual respect existing among the participants
Other authorsSee publication -
Shifts in replication timing actively affect histone acetylation during nucleosome reassembly.
Mol Cell
The entire genome is replicated in a programmed manner, with specific regions undergoing DNA synthesis at different times in S phase. Active genes generally replicate in early S phase, while repressed genes replicate late, and for some loci this process is developmentally regulated. Using a nuclear microinjection system, we demonstrate that DNA sequences originally packaged into nucleosomes containing deacetylated histones during late S become reassembled with acetylated histones after…
The entire genome is replicated in a programmed manner, with specific regions undergoing DNA synthesis at different times in S phase. Active genes generally replicate in early S phase, while repressed genes replicate late, and for some loci this process is developmentally regulated. Using a nuclear microinjection system, we demonstrate that DNA sequences originally packaged into nucleosomes containing deacetylated histones during late S become reassembled with acetylated histones after undergoing replication in early S. Conversely, a change from early to late replication timing is accompanied by repackaging into nucleosomes containing deacetylated histones. This is carried out by differential cell-cycle-controlled acetylation and deacetylation of histones H3 and H4. These studies provide strong evidence that switches in replication timing may play a role in the regulation of nucleosome structure during development
Other authorsSee publication -
Role of DNA methylation in stable gene repression.
J Biol Chem
A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-)(/)(-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to…
A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-)(/)(-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to additional repression mechanisms that also impact on histone acetylation, and the data suggest that late replication timing may play an important role in this process
Other authorsSee publication -
Silence of the genes--mechanisms of long-term repression.
Nat Rev Genet
A large fraction of genes in the mammalian genome is repressed in every cell throughout development. Here, we propose that this long-term silencing is carried out by distinct molecular mechanisms that operate in a global manner and, once established, can be maintained autonomously through DNA replication. Both individually and in combination these mechanisms bring about repression, mainly by lowering gene accessibility through closed chromatin structures.
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The imprinting mechanism of the Prader-Willi/Angelman regional control center
EMBO J
The 2 Mb domain on chromosome 15q11-q13 that carries the imprinted genes involved in Prader-Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS-SRO located around the SNRPN promoter and the AS-SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS-SRO is sensitive to DNase I, and packaged with acetylated histone H4 and…
The 2 Mb domain on chromosome 15q11-q13 that carries the imprinted genes involved in Prader-Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS-SRO located around the SNRPN promoter and the AS-SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS-SRO is sensitive to DNase I, and packaged with acetylated histone H4 and methylated histone H3(K4) only on the maternal allele, and this imprinted epigenetic structure is maintained in dividing cells despite the absence of clearcut differential DNA methylation. Genetic analysis shows that the maternal AS-SRO is essential for setting up the DNA methylation state and closed chromatin structure of the neighboring PWS-SRO. In contrast, the PWS-SRO has no influence on the epigenetic features of the AS-SRO. These results suggest a stepwise, unidirectional program in which structural imprinting at the AS-SRO brings about allele-specific repression of the maternal PWS-SRO, thereby preventing regional activation of genes on this allele.
Other authorsSee publication -
Developmental regulation of DNA replication timing at the human beta globin locus
EMBO J.
The human beta globin locus replicates late in most cell types, but becomes early replicating in erythroid cells. Using FISH to map DNA replication timing around the endogenous beta globin locus and by applying a genetic approach in transgenic mice, we have demonstrated that both the late and early replication states are controlled by regulatory elements within the locus control region. These results also show that the pattern of replication timing is set up by mechanisms that work…
The human beta globin locus replicates late in most cell types, but becomes early replicating in erythroid cells. Using FISH to map DNA replication timing around the endogenous beta globin locus and by applying a genetic approach in transgenic mice, we have demonstrated that both the late and early replication states are controlled by regulatory elements within the locus control region. These results also show that the pattern of replication timing is set up by mechanisms that work independently of gene transcription
Other authorsSee publication
Projects
Honors & Awards
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PharmaVOICE 100 Most Inspiring People
PharmaVOICE 100
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Alice and Joseph E. Brooks Fellowship
Harvard Medical School
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Dean’s list for excellent students
Hebrew University Medical School
(Top 5% of class GPA)
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Luxembourg Prize for foreign excellent students
Luxembourg Foundation
Luxembourg Prize for foreign excellent students
Languages
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Englisch
Native or bilingual proficiency
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Spanish
Native or bilingual proficiency
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Hebrew
Native or bilingual proficiency
More activity by Laura
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This #WomensEqualityDay, we're celebrating the amazing women at Hello Heart. We're proud to be a women-led company and even prouder to support…
This #WomensEqualityDay, we're celebrating the amazing women at Hello Heart. We're proud to be a women-led company and even prouder to support…
Liked by Laura Lande-Diner
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An exciting day for Bifrost Biosystems!
An exciting day for Bifrost Biosystems!
Liked by Laura Lande-Diner
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This is a key milestone in the long journey looking for and developing a therapy for Prader Willi Syndrome. Congratulations to Anish, Neil and the…
This is a key milestone in the long journey looking for and developing a therapy for Prader Willi Syndrome. Congratulations to Anish, Neil and the…
Liked by Laura Lande-Diner
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“You can’t life without enjoying life.” Today I recorded a conversation with my daughter Mia Kogan-Spivack for my new REINVENT•ABILITY podcast…
“You can’t life without enjoying life.” Today I recorded a conversation with my daughter Mia Kogan-Spivack for my new REINVENT•ABILITY podcast…
Liked by Laura Lande-Diner
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Why have there been so many failed experiments amongst Big Tech companies in health care? I speak on this topic with the true experts - Luba…
Why have there been so many failed experiments amongst Big Tech companies in health care? I speak on this topic with the true experts - Luba…
Liked by Laura Lande-Diner
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Thank you Max Sederer! It was our pleasure to host our colleagues from Northeastern University! Our years-long partnership has been a wonderful one…
Thank you Max Sederer! It was our pleasure to host our colleagues from Northeastern University! Our years-long partnership has been a wonderful one…
Liked by Laura Lande-Diner
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Do clinicians make good healthcare investors? YES. They’re heroic🦸♀️but also deliver MOIC📈. This week I scrubbed 🔬 in with the Second Opinion…
Do clinicians make good healthcare investors? YES. They’re heroic🦸♀️but also deliver MOIC📈. This week I scrubbed 🔬 in with the Second Opinion…
Liked by Laura Lande-Diner
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We are thrilled to celebrate Maria-Jesus Blanco, SVP, Head of Drug Discovery, on her incredible achievement of being inducted into the ACS Division…
We are thrilled to celebrate Maria-Jesus Blanco, SVP, Head of Drug Discovery, on her incredible achievement of being inducted into the ACS Division…
Liked by Laura Lande-Diner
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Ellen Roche is creating the next generation of medical devices to help repair hearts, lungs, and other tissues. Some, such as a soft robotic…
Ellen Roche is creating the next generation of medical devices to help repair hearts, lungs, and other tissues. Some, such as a soft robotic…
Liked by Laura Lande-Diner
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So proud of the team! This funding recognizes all our the innovative work and underscores the need to of address the "undruggable" transcription…
So proud of the team! This funding recognizes all our the innovative work and underscores the need to of address the "undruggable" transcription…
Liked by Laura Lande-Diner
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