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  • Faculty
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  • Juan R Alvarez
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Faculty

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Juan R Alvarez, PhD

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Assistant Professor of Cell and Developmental Biology
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Department: Cell and Developmental Biology
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1f Graduate Group Affiliations 8 a
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46 Contact information
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9-102 Smilow Center for Translational Research
39 3400 Civic Center Blvd
Philadelphia, PA 19104
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Email: juan.alvarez@pennmedicine.upenn.edu
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18 Publications
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13 Education:
21 9 B.A. 1e (Molecular Biology) c
2d Princeton University, 2009.
 21 a Ph.D. 14 (Biology) c
3e Massachusetts Institute of Technology, 2015.
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Links
c2 Search PubMed for articles
 73 Freeman Hrabowski Scholar
4a Lab Website
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5 3 3 92 Permanent link
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b6 > Perelman School of Medicine   > Faculty   > Details a
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Description of Research Expertise

3a Research Interests

Chronobiology
24 Pancreatic islet development
1d Regenerative medicine
23 Gene & chromatin regulation
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d8 Keywords: circadian biology, stem cell-derived organoids, lineage development, cell maturation, pancreatic islets, single-cell omics, regenerative medicine, gene regulation, epigenetics, non-coding RNA
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23 Research Description
246 Our laboratory investigates how biological rhythms shape the functional maturation of differentiated cells. We use genetic and engineering tools to chart, navigate, and control how cell molecular and functional states synchronize and evolve during maturation, leveraging mice and human organoid models. Our goal is to understand how circadian and metabolic cycles regulate cell maturity, and to engineer multimodal approaches to sense and control cell rhythms, which we use to make fully functional pancreatic islet organoids for diabetes research and regenerative medicine.
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37 Our work addresses three fundamental questions:
44 1. How do cells and tissues become functionally specialized?
48 2. How does organ-level physiology entrain to circadian rhythms?
5a 3. How do circadian disturbances lead to organ and systemic metabolic dysfunction?
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15d 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.
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1f Rotation Projects
3d 1. Organoid maturation by daily metabolic entrainment
3b 2. Circadian rhythm development across body tissues
52 3. Gene, chromatin, and translation circuits governing Beta-cell maturity
46 4. Design principles governing islet function and connectivity
73 5. Charting human islet maturation via combined soft nanoelectronics and single-cell spatial transcriptomics
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Selected Publications

e2 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.

 19e 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 Notes: Nature Communications: Aug 8 2025 revision invited (due within 6 months).

 1c5 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 Notes: Nature Methods: Aug 11 2025 agreed on plan for requested revision.

 112 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.

 123 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.

 e9 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.

 c0 Alvarez-Dominguez JR*, Melton DA.: Cell maturation: Hallmarks, triggers, and manipulation. Cell 185: 235-249, Jan 2022.

 129 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.

 e5 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.

 128 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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