University of Wisconsin-Madison UW-Madison

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Barak Blum

Associate Professor of Cell and Regenerative Biology

School of Medicine and Public Health

Organogenesis and functional maturation of the islets of Langerhans in the pancreas.

Phone

(608) 265-5211

Email

bblum4@wisc.edu

Website

https://blum.crb.wisc.edu/

Office Location

4551 WIMR II

1111 Highland Ave

Madison, WI 53705

B.Sc., Life Sciences, Ben-Gurion University of the Negev, Israel
M.Sc., Medical Biochemistry, The Hebrew University of Jerusalem, Israel
Ph.D., Genetics, The Hebrew University of Jerusalem
Postdoctoral Research, Stem Cell and Regenerative Biology, Harvard University

Representative Publications

  • Adams MT, Waters BJ, Nimkulrat SD, Blum B. Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo βKO mice. FASEB J. 2023 Aug;37(8):e23106. doi: 10.1096/fj.202200705RR. PMID: 37498234; PMCID: PMC10436995.
  • Waters BJ, Blum B. Axon Guidance Molecules in the Islets of Langerhans. Front Endocrinol (Lausanne). 2022 Apr 14;13:869780. doi: 10.3389/fendo.2022.869780. PMID: 35498433; PMCID: PMC9048200.
  • Adams MT, Blum B. Determinants and dynamics of pancreatic islet architecture. Islets. 2022 Dec 31;14(1):82-100. doi: 10.1080/19382014.2022.2030649. PMID: 35258417; PMCID: PMC8920234.
  • Nimkulrat SD, Bernstein MN, Ni Z, Brown J, Kendziorski C, Blum B. The Anna Karenina Model of β-Cell Maturation in Development and Their Dedifferentiation in Type 1 and Type 2 Diabetes. Diabetes. 2021 Sep;70(9):2058-2066. doi: 10.2337/db21-0211. Epub 2021 Jun 15. PMID: 34417264; PMCID: PMC8576426.
  • Adams MT, Dwulet JM, Briggs JK, Reissaus CA, Jin E, Szulczewski JM, Lyman MR, Sdao SM, Kravets V, Nimkulrat SD, Ponik SM, Merrins MJ, Mirmira RG, Linnemann AK, Benninger RK, Blum B. Reduced synchroneity of intra-islet Ca2+ oscillations in vivo in Robo-deficient β cells. Elife. 2021 Jul 7;10:e61308. doi: 10.7554/eLife.61308. PMID: 34231467; PMCID: PMC8289414.
  • Sdao SM, Ho T, Poudel C, Foster HR, De Leon ER, Adams MT, Lee JH, Blum B, Rane SG, Merrins MJ. CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent KATP channel closure. Cell Rep. 2021 Jan 26;34(4):108690. doi: 10.1016/j.celrep.2021.108690. PMID: 33503433; PMCID: PMC7882066.
  • Gilbert JM, Adams MT, Sharon N, Jayaraaman H, Blum B. Morphogenesis of the Islets of Langerhans Is Guided by Extraendocrine Slit2 and Slit3 Signals. Mol Cell Biol. 2021 Feb 23;41(3):e0045120. doi: 10.1128/MCB.00451-20. Epub 2020 Dec 14. PMID: 33318057; PMCID: PMC8088276.
  • Adams, M. T., Gilbert, J. M., Paiz, J. H., Bowman, F. M., & Blum, B. (2018). Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells. Scientific Reports, 8(1). doi:10.1038/s41598-018-29118-x
  • Gilbert, J. M., & Blum, B. (2018). Synaptotagmins Tweak Functional β Cell Maturation. Developmental Cell,45(3), 284-286. doi:10.1016/j.devcel.2018.04.018
  • Blum, B., Roose, A.N., Barrandon, O., Maehr, R., Arvanites, A.C., Davidow, L.S., Davis, J.C., Peterson, Q.P., Rubin, L.L., Melton, D.A., (2014) Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway. eLife, e02809
  • Blum, B., Hrvatin, S., Schuetz, C., Bonal, C., Rezania, A., Melton, D.A., (2012) Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3. Nat. Biotechnol., 30:261-264

PubMed

How does a newly formed stem or progenitor cell “know” it had reached its full differentiation capacity, and should assume its mature function? What part of the signal towards terminal differentiation comes from the cell’s interactions with its surrounding environment, and what is encoded in the blueprint of its intrinsic developmental program? How is this functionally mature state, once achieved, sustained throughout adult life, or tip off balance and erode in degenerative disease? And what exactly is a fully differentiated, functionally mature cell state? Not only do these questions represent fundamental problems in developmental biology, but they are also crucial in regenerative medicine, where one wants to impose a functionally mature phenotype upon stem cells differentiated in vitro, or prevent the loss of the mature cell state in degenerative diseases.

Our lab uses human pluripotent stem cells differentiation, developmental biology of the pancreas, mouse genetics, bioinformatics and functional genomic analyses to discover the genetic and molecular regulatory circuits controlling the development, maintenance, collapse and recovery of the fully differentiated, functionally mature β cell state in mice and humans.

Expanding our knowledge of functional β cell maturation will have an important impact on both stem cell based therapy for type-1 diabetes and on the prevention of irreversible β cell de-differentiation in type-2 diabetes. Specifically, it may lead to the ability to genetically set naive β cells differentiated from stem cells in vitro to produce and secrete exactly the right amount of insulin in response to a given concentration of glucose, as well as to prevent de-differentiation and maintain functional β cell maturation in diabetics.

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