PEOPLE

Bryan A. Wolf, MD, PhD

Professor of Pediatrics, Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine
Executive Vice President and Chief Scientific Officer, CHOP

Contact InformationThe Children's Hospital of Philadelphia
Executive Offices
1415 Abramson Building
34th Street and Civic Center Boulevard
Philadelphia, PA, 19104-4399
Office: (215) 590-2869

Email: WOLFB@MAIL.MED.UPENN.EDU

Specialty Division

Immunobiology and Experimental Pathology

Research Expertise

Research Interests
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

Lab personnel:
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

Education

(French High-school diploma in Math and Science), Baccalaureate C, Lycée Montaigne, Paris, France, 1976
M.Sc. (Pharmacology), University of Paris Jussieu, Institute of Pharmacology, Paris, France, 1982
M.D. (Necker-Enfants-Malades), University of Paris-Rene-Descartes, Paris, France, 1983
Ph.D. (Nutrition/Endocrinology), University of Paris-Jussieu, Paris, France, 1984
M.A. (Honorary), University of Pennsylvania, Philadelphia, PA, 1996

Specialty Certification

Diplomate, American Board of Pathology in clinical pathology, 1992

Postgraduate Training

Post-doctoral Research Fellow (Biochemistry), Department of Pathology , Washington University School of Medicine, St. Louis, Missouri, 1984-1987
Resident in Laboratory Medicine, Division of Laboratory Medicine, Departments of Pathology and Internal Medicine, Barnes Hospital, Washington University School of Medicine, 1987-1990
Post-doctoral Research Fellow (Biochemistry), Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, Missouri, 1988-1990
Chief Fellow in Clinical Chemistry , Barnes Hospital, St. Louis, Missouri, 1989-1990

Awards and Honors

Nordisk Insulin Laboratorium Grant for the Study of Growth, Gentofte, Denmark, 1981-1983
Medical Research Foundation Grant, Paris, France, 1983-1984
Ph.D. thesis with honors, 1984
National Research Service Award (T32 AM07296), NIDDK (Endocrinology/Diabetes), 1984-1986
Endocrine Society Travel Award, 1986
National Research Service Award (individual) (F32 DK07748-01), NIDDK (Endocrinology/Diabetes), 1986
Juvenile Diabetes Foundation Fellowship, 1986-1987
Young Investigator Award, Academy of Clinical Laboratory Physicians and Scientists, 1989
Career Development Award, Juvenile Diabetes Foundation, 1990
Research and Development Award, American Diabetes Association, 1990-1993
Award for Outstanding Scientific Achievements by a Young Investigator, American Association of Clinical Chemistry, 1992
Hartford Foundation Fellow, 1993-1994
Research and Career Development Award, National Institutes of Health, 1994-1998

Memberships and Professional Organizations

American Diabetes Association (1985), 1985 - 2009
American Association for the Advancement of Science (1985), 1985 - 2009
American Society for Biochemistry and Molecular Biology, Inc. (1986), 1986 - 2008
American Association for Clinical Chemistry, Inc. (1989), 1989 - 2008
European Association for the Study of Diabetes (1990), 1990 - 2008
International Association of Therapeutic Drug Monitoring and Clinical Toxicology (1991), 1991 - 2008
Academy of Clinical Laboratory Physicians and Scientists (1991), 1991 - 2008
Juvenile Diabetes Research Foundation Internaltional, 1998 - 2008
American Society for Clinical Investigation, 2001 - Present
American Society for Investigative Pathology, 2001 - 2008
College of American Pathologists (2003), 2003 - 2009
College of Healthcare Information Management Executives, 2009 - Present

Web Links


Selected Publications

Distinguishing features of leucine and alpha-ketoisocaproate sensing in pancreatic beta-cells

Gao Z., Young RA., Li G., Najafi H., Buettger C., Sukumvanich SS., Wong RK., Wolf BA., Matschinsky FM., Endocrinology 144(5): 1949-57, 2003, PMID:12697702

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Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells

Borge PD Jr., Wolf BA., Journal of Biological Chemistry 278(13): 11359-68, 2003

Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity?

Desai NM., Goss JA., Deng S., Wolf BA., Markmann E., Palanjian M., Shock AP., Feliciano S., Brunicardi FC., Barker CF., Naji A., Markmann JF., Transplantation 76(11): 1623-5, 2003

Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets

Bell E., Cao X., Moibi JA., Greene SR., Young R., Trucco M., Gao Z., Matschinsky FM., Deng S., Markman JF., Naji A., Wolf BA., Diabetes 52(11): 2731-9, 2003

Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells

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., Diabetes 52(9): 2296-303, 2003

Insulin gene transfer enhances the function of human islet grafts

Deng S., Vatamaniuk M., Lian MM., Doliba N., Wang J., Bell E., Wolf B., Raper S., Matschinsky FM., Markmann JF., Diabetologia 46(3): 386-93, 2003, PMID:12687337

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Insulin independence following isolated islet transplantation and single islet infusions

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., Annals of Surgery 237(6): 741-9; discussion 749-50, 2003, PMID:12796569

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The use of non-heart-beating donors for isolated pancreatic islet transplantation

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., Transplantation 75(9): 1423-9, 2003, PMID:12792491

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Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis

Gao Z., Young RA., Trucco MM., Greene SR., Hewlett EL., Matschinsky FM., Wolf BA., Biochemical Journal 368(Pt 2): 397-404, 2002

Glucose-dependent promotion of insulin release from mouse pancreatic islets by the insulin-mimetic compound L-783,281

Westerlund J., Wolf BA., Bergsten P., Diabetes 51 Suppl 1(): S50-2, 2002

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