Signaling mechanisms of insulin secretion. Cytokines and diabetes.
Key words: Insulin secretion, diabetes, cytokine, signal transduction.
Description of Research
My research lab is focused on the signal transduction mechanisms of insulin secretion from the islets of Langerhans within the context of understanding diabetes. Recently, we have identified a novel cytokine called PANDER (FAM3B) which is one of 4 cytokines of a new gene family FAM3. Veryl little is known about the cell biology of PANDER and the role of PANDER in islet biology. PANDER is expressed in islets of Langerhans and is present in secretory granules. PANDER causes apoptosis of beta-cells. PANDER mRNA is upregulated by interferon-gamma treatment in beta-cells. We have 2 working hypotheses that we are testing: is PANDER involved in cytokine-induced destruction of islets and the pathogenesis of type 1 diabetes, does PANDER have any role in beta-cell differentiation? The lab is using a combination of cell biological, biochemical and molecular biology approaches to understand the physiological role of PANDER and its role in diabetes.
Rotation Projects for 2006-2007
- Analysis of PANDER transgenic mouse
- Site-directed mutagenesis of PANDER
- siRNA approaches to downregulate PANDER
- Regulation of PANDER mRNA in beta-cells
- Secretory mechanisms of PANDER in beta-cells
Brant Burkhardt, PhD, Postdoctoral Fellow
Joshua Cook, Penn Undergraduate Student
Zhiyong Gao, MD, PhD, Lab Manager
Jason Carnegie, Graduate student (CAMB)
Scott Greene, Research Specialist
Claudia Robert, Graduate Student (CAMB)
Kelly McFadden, Penn Undergraduate Student
Jianmei Wu, Research Specialist
Jichun Yang, PhD, Postdoctoral Fellow
Robert Young, Research Specialist
- Professor of Pediatrics at University of Pennsylvania School of Medicine (2002– present)
- Assistant Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (1990 – 1996)
- Associate Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (1996 – 2001)
- Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2001– present)
- M.A., Honorary, University of Pennsylvania, Philadelphia, PA (1996)
- Ph.D., Nutrition/Endocrinology, University of Paris-Jussieu, Paris, France (1984)
- M.D., Necker-Enfants-Malades, University of Paris-Rene-Descartes, Paris, France (1983)
- M.Sc., Pharmacology, University of Paris Jussieu, Institute of Pharmacology, Paris, France (1982)
- Gao Z., Young RA., Li G., Najafi H., Buettger C., Sukumvanich SS., Wong RK., Wolf BA., Matschinsky FM.. Distinguishing features of leucine and alpha-ketoisocaproate sensing in pancreatic beta-cells. Endocrinology. Vol 144(5) . 2003 May:1949-57.
- Borge PD Jr., Wolf BA.. Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells. Journal of Biological Chemistry. Vol 278(13) . 2003 Mar 28:11359-68.
- Desai NM., Goss JA., Deng S., Wolf BA., Markmann E., Palanjian M., Shock AP., Feliciano S., Brunicardi FC., Barker CF., Naji A., Markmann JF.. Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity?. Transplantation. Vol 76(11) . 2003 Dec 15:1623-5.
- Bell E., Cao X., Moibi JA., Greene SR., Young R., Trucco M., Gao Z., Matschinsky FM., Deng S., Markman JF., Naji A., Wolf BA.. Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes. Vol 52(11) . 2003 Nov:2731-9.
- Cao X., Gao Z., Robert CE., Greene S., Xu G., Xu W., Bell E., Campbell D., Zhu Y., Young R., Trucco M., Markmann JF., Naji A., Wolf BA.. Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells. Diabetes. Vol 52(9) . 2003 Sep:2296-303.
- Deng S., Vatamaniuk M., Lian MM., Doliba N., Wang J., Bell E., Wolf B., Raper S., Matschinsky FM., Markmann JF.. Insulin gene transfer enhances the function of human islet grafts. Diabetologia. Vol 46(3) . 2003 Mar:386-93.
- Markmann JF., Deng S., Huang X., Desai NM., Velidedeoglu EH., Lui C., Frank A., Markmann E., Palanjian M., Brayman K., Wolf B., Bell E., Vitamaniuk M., Doliba N., Matschinsky F., Barker CF., Naji A.. Insulin independence following isolated islet transplantation and single islet infusions. Annals of Surgery. Vol 237(6) . 2003 Jun:741-9; discussion 749-50.
- Markmann JF., Deng S., Desai NM., Huang X., Velidedeoglu E., Frank A., Liu C., Brayman KL., Lian MM., Wolf B., Bell E., Vitamaniuk M., Doliba N., Matschinsky F., Markmann E., Barker CF., Naji A.. The use of non-heart-beating donors for isolated pancreatic islet transplantation. Transplantation. Vol 75(9) . 2003 May 15:1423-9.
- Gao Z., Young RA., Trucco MM., Greene SR., Hewlett EL., Matschinsky FM., Wolf BA.. Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis. Biochemical Journal. Vol 368(Pt 2) . 2002 Dec 1:397-404.
- Westerlund J., Wolf BA., Bergsten P.. Glucose-dependent promotion of insulin release from mouse pancreatic islets by the insulin-mimetic compound L-783,281. Diabetes. Vol 51 Suppl 1. 2002 Feb:S50-2.