Barak Blum, PHD

Pubmed

More information:

• Barak Blum’s Cell and Regenerative Biology department webpage

Research Description:

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? And how is this functionally mature state, once achieved, sustained throughout adult life, or tip off balance and erode in degenerative disease?

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

Expanding our knowledge of functional beta cell maturation will have an important impact on both stem cell based therapy for type-1 diabetics and on the prevention of irreversible beta cell de-differentiation in type-2 diabetes.

Selected References:

• Adams MT, Gilbert JM, Hinojosa Paiz J, Bowman FM, Blum B. Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells. Sci Rep. 2018 Jul 18;8(1):10876. doi: 10.1038/s41598-018-29118-x.
• Adams, M.T., Reissaus, C.A., J.M., Dwulet, Jin, E., Joseph M. Szulczewski, J.M., Lyman, M.R., Sdao, S.M., Nimkulrat, S.D., Ponik, S.M., Merrins, M.J., Benninger, R.K.P., Mirmira, R.G., Linnemann, A.K., Blum, B. Reduced synchroneity of intra-islet Ca²⁺ oscillations in vivo in Robo-deficient β cells. eLife 10:e61308 (2021)
• 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
• Nimkulrat, S.D., 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 in press. (2021)