Research & Clinical Summary
The overall objective of our team is to study mechanisms that regulate the development and function of a specialized type of pancreatic cells, known as β-cells, that are responsible for the production of insulin, and whose function is lost in type 1 diabetes, or altered in type 2 diabetes. A major area of focus in the lab is to understand the function of proteins that regulate cell-cell and cell-matrix interactions in the pancreas. These proteins, also referred to as “cell adhesion molecules,” are used by cells not only to aggregate with each other, but also to let cells talk to one another through the exchange of biochemical signals, thereby helping developing/immature cells to decide whether to grow (i.e. increase in numbers) or to differentiate (i.e. mature) into functional adult β-cells. In an effort to develop strategies of possible translational value to human diabetes, our team is using a multipronged approach. On the one hand, we are trying to understand if tissue donor-derived immature pancreatic cells can be coaxed to produce insulin upon stimulation with molecules that foster cell-cell and/or cell-matrix interactions. On the other hand, recombinant cell adhesion molecules that we are producing in the lab are used as biochemical cues to test whether they can trigger the maturation of stem cells to become insulin-producing β-cells, or to trigger the proliferation of adult β-cells, thus increasing their number before transplantation, or promote their regeneration in diabetic patients.
Interests: Endocrinology & Nutrition, Metabolism, Metabolome
Publications
The following publications were retrieved from PubMed:
Mussar K, Tucker A, McLennan L, Gearhart A, Jimenez-Caliani AJ, Cirulli V, Crisa L,
“Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.”
PloS one 9.2 (2014): e89492.
Ware CB, Nelson AM, Mecham B, Hesson J, Zhou W, Jonlin EC, Jimenez-Caliani AJ, Deng X, Cavanaugh C, Cook S, Tesar PJ, Okada J, Margaretha L, Sperber H, Choi M, Blau CA, Treuting PM, Hawkins RD, Cirulli V, Ruohola-Baker H,
“Derivation of naive human embryonic stem cells.”
Proceedings of the National Academy of Sciences of the United States of America 111.12 (2014 Mar 25): 4484-9.
Cirulli V,
“Cadherins in islet β-cells: more than meets the eye.”
Diabetes 64.3 (2015 Mar): 709-11.
Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S, Haataja L, Cirulli V, Blelloch R, Szot GL, Arvan P, Hebrok M,
“Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro.”
The EMBO journal 34.13 (2015 Jul 2): 1759-72.
Vercollone JR, Balzar M, Litvinov SV, Yang W, Cirulli V,
“MMTV/LTR Promoter-Driven Transgenic Expression of EpCAM Leads to the Development of Large Pancreatic Islets.”
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 63.8 (2015 Aug): 613-25.
Shih HP, Panlasigui D, Cirulli V, Sander M,
“ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis.”
Cell reports 14.2 (2016 Jan 12): 169-79.