The Odorico Laboratory
Faculty > Jon S. Odorico
Jon S. Odorico
Associate Professor, Surgery
jon@surgery.wisc.edu
Research Description
Our lab studies pancreatic lineage differentiation, including the differentiation of insulin-producing islet endocrine cells, from embryonic stem cells (ESCs). The work is designed to address two critical needs. First is the need to generate an unlimited supply of functional insulin-secreting beta cells to be used to replace damaged beta cells in patients with diabetes. Second is the need for a cell culture model to study, specifically, human pancreas and islet development, given known differences in pancreas and islet organ formation between humans and lower organisms and the inability to study human organ development in vivo.
The first step in achieving these two goals was to simply test whether ESCs from various species can become pancreatic cell types. We and others have recently demonstrated that murine, rhesus, and human ESCs are in fact capable of committing to a pancreatic progenitor cell fate defined by cells expressing pancreatic duodenal homeobox 1 (PDX1) via an endoderm pathway. Ultimately, progenitor cells can give rise to islet endocrine cells expressing insulin, glucagon, and somatostatin. (Kahan et al. Diabetes 2003, Jacobson et al 2001, Xu et al Stem Cells and Development 2006).
Current work in the lab focuses on identifying key extrinsic signals regulating early endoderm fate of human ESCs in order to develop culture protocols that selectively enrich for pancreatic lineage cells. Populations of insulin-expressing cells are being studied using functional assays that are established in the lab comparing them to adult human islets in their ability to reverse diabetes. We are also interested in exploring whether such cells might be less immunogenic than adult islets, which would have significant clinical implications. In addition, we are actively developing a sorting method that both enriches ESC cultures for foregut committed cells and reduces the tendency of ESC derivatives to form teratomas after transplantation, a process that could be used to improve the safety of transplanted cells. Other projects in the lab are evaluating the roles of key pancreatic transcription factors, such as Ngn3, Ptf1a, HNF6 and others in directing pancreatic differentiation from ESCs.
Selected References
Vincent R, Treff N, Budde M, Kastenberg Z, Odorico J. Generation and characterization of novel tetracycline-inducible pancreatic transcription factor-expressing murine embryonic stem cell lines. Stem Cells Dev. 15(6):953-62. 2006.
Magliocca JF, Held IK, Odorico JS. Undifferentiated murine embryonic stem cells cannot induce portal tolerance but may possess immune privilege secondary to reduced major histocompatibility complex antigen expression.
Stem Cells Dev. 15(5):707-17. 2006.
Barth RN, Janus CA, Lillesand CA, Radke NA, Pirsch JD, Becker BN, Fernandez LA, Thomas Chin L, Becker YT, Odorico JS, D'Alessandro AM, Sollinger HW, Knechtle SJ.
Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transpl Int. 19(11):885-92. 2006.
Mohanakumar T, Narayanan K, Desai N, Ramachandran S, Shenoy S, Jendrisak M, Susskind BM, Olack B, Benshoff N, Phelan DL, Brennan DC, Fernandez LA, Odorico JS, Polonsky KS.
A significant role for histocompatibility in human islet transplantation. Transplantation. 27;82(2):180-7. 2006.
Treff NR, Vincent RK, Budde ML, Browning VL, Magliocca JF, Kapur V, Odorico JS.
Differentiation of embryonic stem cells conditionally expressing neurogenin 3. Stem Cells. 24(11):2529-37. 2006.
Kim K-H, Kim T-G, Micales B, Lyons GE, Lee Y. Dynamic expression patterns of Leucine Rich Repeat containing protein 10 in the heart. Developmental Dynamics 236:2225-234. 2007.