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René Salazar Speaker Series: "Chrono-energetics: Linking Circadian Metabolism to Islet Replacement Therapeutics." on 4/9
Please join LatinX@Broad in promoting and highlighting diversity in academic disciplines within and outside the Broad. Register for our next talk, to be held Tuesday, April 9th, 2024.
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René Salazar Speaker Series

Join us for our next scheduled René Salazar Speaker Series talk held by LatinX@Broad:

"Chrono-energetics: Linking Circadian Metabolism to Islet Replacement Therapeutics."

Tuesday, April 9th, 2024
2:00-3:00 pm
Zoom 


Registration required via Zoom, to register please visit: http://broad.io/LatinX_Talks 

Dr. Juan Alvarez
Assistant Professor of Cell and Developmental Biology
Department of Cell and Developmental Biology

University of Pennsylvania

Abstract

Rhythms in energy availability, driven by earth’s 24-hour rotation, are the oldest, most consistent external input for life on earth. All life forms (from bacteria to all of our cells) have thus evolved autonomous “circadian” clocks that align physiologyfrom nutrient transport and uptake to breakdown and storage - to daily feeding-fasting. Chronic misalignment between endogenous and external rhythms triggers multi-system dysfunction, including metabolic, cardiovascular, and neural syndromes. Common to such diverse disorders is the loss of specialised cell phenotypes, suggesting that timing cellular tasks to daily energy cycles is vital for mature functioning.

Our tissues mature along with daily environment fluctuations, yet organoids today are grown in constant environments. Most efforts to foster organoid maturation have focused on the nature, not the timing, of maturational cues, despite the built-in rhythmicity of cellular processes. Thus, to better understand and harness maturation, we must shift from “static” to “rhythmic” paradigms.

Recently, Dr. Alvarez discovered that daily feeding rhythms can foster maturation of SC-islets (human stem cell-derived islets), which functioned in vivo within days of transplant. This provided the first proof-of-principle that rhythms can be harnessed to engineer mature organoids for regenerative medicine. He now seeks to follow up on this research to dissect the underlying molecular mechanisms, to robustly generate mature organoids, and to further their use as research models and diabetes replacement therapy.

His lab focuses on understanding how rhythms regulate cell maturation, to enable creating fully functional organoids for tissue replacement therapies. Specifically, we aim to:

1) Link chrono-energetic mechanisms to SC-islet cell maturation trajectories, integrating novel tissue engineering and single-cell approaches that leverage my cross-disciplinary expertise in cell fate control and gene regulation.

2) Harness these mechanisms for disease-modeling, screening, and therapeutic applications via functional laboratory experiments and animal transplantation studies.

These studies will reveal the principles by which circadian rhythms shape islet maturation, which will help us understand, and eventually prevent, its loss during diabetes and chrono-disruption. Unlocking these principles may also illuminate general means to harness control over maturity of any human tissue.


Speaker Bio

Dr. Alvarez is an Assistant Professor of Cell and Developmental Biology at the University of Pennsylvania Perelman School of Medicine, and member of Penn’s Institutes for Diabetes, Obesity and Metabolism, Chronobiology and Sleep, and Regenerative Medicine. 

Dr. Alvarez's research focuses on the interplay between metabolic cycles, circadian oscillators, and islet maturation. This work involves single-cell and high-throughput experimental and computational approaches, with a view to rationally engineer mature stem cell-derived islet organoids as human models of islet development & physiology, and as a novel replacement therapy for insulin-dependent diabetics.

Dr. Alvarez completed an HHMI LSRF Research Fellowship with the Melton group at Harvard University, asking How circadian rhythms shape islet development and diabetes, using human organoids and mouse models. He received his PhD in biology from MIT, where he studied the modulation of lineage-specific cell differentiation by long non-coding RNAs, and his AB in molecular biology from Princeton University, where he studied the role of DNA self-catalytic depurination in site-specific mutagenesis.

Questions? Email latinx-sc@broadinstitute.org.

 

 

René Salazar Speaker Series