Juan R Alvarez, PhD
3400 Civic Center Blvd
Philadelphia, PA 19104
B.A. (Molecular Biology)
Princeton University, 2009.
Massachusetts Institute of Technology, 2015.
Description of Research ExpertiseResearch Interests
Gene & chromatin regulation
Human islet development
Keywords: diabetes, regenerative biology, cell maturation, lineage development, islets, stem cell-derived organoids, circadian clock, single-cell omics, gene regulation, epigenetics, non-coding RNA
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.
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 PublicationsAlvarez-Dominguez JR, Melton DA.: Cell maturation: Hallmarks, triggers, and manipulation. Cell 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.
Alvarez-Dominguez, J.R., Donaghey, J., Rasouli, N., Kenty, J.H.R., Helman, A., Charlton, J., Straubhaar, J.R., Meissner, A., and Melton, D.A.: Organoid Maturation by Circadian Entrainment. StemJournal 2: 7-13, 2020.
Xu D, Xu S, Kyaw AMM, Lim YC, Chia SY, Chee Siang DT, Alvarez-Dominguez JR, Chen P, Leow MK, Sun L.: RNA Binding Protein Ybx2 Regulates RNA Stability During Cold-Induced Brown Fat Activation. Diabetes 66(12): 2987-3000, Dec 2017.
Alvarez-Dominguez JR, Lodish HF.: Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis. Blood 130: 1965-1975, Nov 2017.
Alvarez-Dominguez JR, Knoll M, Gromatzky AA, Lodish HF.: The Super-Enhancer-Derived alncRNA-EC7/Bloodlinc Potentiates Red Blood Cell Development in trans. Cell Rep 19: 2503-2514, Jun 2017.
Alvarez-Dominguez JR, Zhang X, Hu W.: Widespread and dynamic translational control of red blood cell development. Blood 129(5): 619-629, Feb 2017.
Atianand MK, Hu W, Satpathy AT, Shen Y, Ricci EP, Alvarez-Dominguez JR, Bhatta A, Schattgen SA, McGowan JD, Blin J, Braun JE, Gandhi P, Moore MJ, Chang HY, Lodish HF, Caffrey DR, Fitzgerald KA.: A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation. Cell 165: 1672-1685, Jun 2016.