Faculty
Juan R Alvarez, PhD
3400 Civic Center Blvd
Philadelphia, PA 19104
B.A. (Molecular Biology)
Princeton University, 2009.
Ph.D. (Biology)
Massachusetts Institute of Technology, 2015.
Description of Research Expertise
Research InterestsRegenerative medicine
Gene & chromatin regulation
Chronobiology
Human pancreatic islet development
Keywords: regenerative medicine, circadian biology, stem cell-derived organoids, lineage development, cell maturation, pancreatic islets, single-cell omics, gene regulation, epigenetics, non-coding RNA
Research Description
Our laboratory uses human stem cell-derived pancreatic islet organoids and mice as model systems to study islet development, physiology, and pathology, and to develop replacement therapies for insulin-dependent diabetes. We focus on the interplay between circadian rhythms, metabolism, and islet cell maturation. Our work addresses three fundamental questions:
1. How do cells and tissues become functionally specialized?
2. How does organ-level physiology entrain to circadian rhythms?
3. How do circadian disturbances lead to organ and systemic metabolic dysfunction?
To this end, we employ single-cell transcriptomic, epigenomic, proteomic methods and genetic, nanoelectronics-based approaches to study and control islet cell fate. We are especially interested in advancing replacement therapies for insulin-dependent diabetes, and harnessing control over the function and applications of any human organoid.
Rotation Projects
1. Gene, chromatin, and translation circuits controlling Beta-cell maturity
2. Organoid maturation by circadian feeding-fasting entrainment
3. Human islet organoids as diabetes replacement therapy
4. Charting human islet maturation via combined soft nanoelectronics and single-cell spatial transcriptomics
5. Design principles governing islet function and connectivity
Selected Publications
Preza S, Zheng B, Gao Z, Liu M, Biju A, Alvarez-Dominguez JR.: DEC1 Regulates Human β Cell Functional Maturation and Circadian Rhythm. bioRxiv Apr 2025.
Montalvo Landivar AP, Gao Z, Liu M, Gruskin ZL, Leduc A, Preza S, Xie Y, Rozo AV, Ahn JH, Straubhaar JR, Doliba N, Stoffers DA, Slavov N, Alvarez-Dominguez JR.: An adult clock regulator links circadian rhythms to pancreatic β-cell maturation. bioRxiv Apr 2025.
Lin Z, Wang W, Marin-Llobet A, Li Q, Pollock SD, Sui X, Aljovic A, Lee J, Baek J, Liang N, Zhang X, Wang CK, Huang J, Liu M, Gao Z, Sheng H, Du J, Lee SJ, Wang B, He Y, Ding J, Wang X, Alvarez-Dominguez JR, Liu J.: Spatial transcriptomics AI agent charts hPSC-pancreas maturation in vivo. bioRxiv Apr 2025.
Li Q, Liu R, Lin Z, Zhang X, Silva IG, Pollock SD, Alvarez-Dominguez JR, Liu J.: Cyborg islets: implanted flexible electronics reveal principles of human islet electrical maturation. bioRxiv Mar 2024.
Pollock SD, Galicia-Silva IM, Liu M, Gruskin ZL, Alvarez-Dominguez JR.: Scalable generation of 3D pancreatic islet organoids from human pluripotent stem cells in suspension bioreactors. STAR Protoc 4: 102715, Dec 2023.
Leavens KF, Alvarez-Dominguez JR, Vo LT, Russ HA, Parent AV.: Stem cell-based multi-tissue platforms to model human autoimmune diabetes. Mol Metab 66, Dec 2022.
Alvarez-Dominguez JR, Melton DA.: Cell maturation: Hallmarks, triggers, and manipulation. Cell 185: 235-249, Jan 2022.
Alvarez-Dominguez, J.R., Winther, S., Hansen, J.B., Lodish, H.F., and Knoll, M.: An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs. iScience 25(1): 103680, Dec 2021.
Rasouli N, Melton DA, Alvarez-Dominguez JR.: Purification of Live Stem-Cell-Derived Islet Lineage Intermediates. Curr Protoc Stem Cell Biol 53(1), Jun 2020.
Alvarez-Dominguez JR, Donaghey J, Rasouli N, Kenty JHR, Helman A, Charlton J, Straubhaar JR, Meissner A, Melton DA.: Circadian Entrainment Triggers Maturation of Human In Vitro Islets. Cell Stem Cell 26: 108-122, Jan 2020.
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