Dr Claire Jessup

Qualifications

BBiotech(Hons); PhD

Teaching Interests

CBL Tutor - Bachelor of Medicine, MLTU, University of Adelaide

Research Interests

ISLET TRANSPLANTATION AND DENDRITIC CELL BIOLOGY LABORATORY

Our laboratory is part of the School of Medicine based in the Department of Nephrology and Transplantation Services (TQEH). The group is run by Prof Graeme Russ and Assoc Prof Toby Coates and our labs are situated in the new state-of-the-art Basil Hetzel Institute for Medicial Research.

Type I diabetes is a chronic, life-long autoimmune disease affecting over 140 000 Australians, where the insulin-producing islets of Langerhans in the pancreas are destroyed. The incidence of this disease is increasing and, even with daily insulin therapy, diabetic patients are at greater risk of serious complications including heart attack, stroke, ocular damage and kidney disease.

Our area of research focuses on the isolation and transplantation of healthy pancreatic islets as an innovative treatment and potential cure for Type I diabetes. As part of the Australian Islet Transplantation Consortium, the laboratory prepares and performs assays on purified islets that are ultimately transplanted into patients. To date, the Consortium has transplanted 15 patients across Australia. Factors limiting the success of islet transplantation include suboptimal engraftment, immune reaction and rapid cell death post transplant. Our laboratory is interested in identifying and combating the causes of islet cell death. We are also interested in basic islet biology, and how function can be protected/quickly restored following transplantation.

 

The laboratory is based in the newly constructed Basil Hetzel Institute at the Queen Elizabeth Hospital site (http://tqeh.sa.gov.au/public/content/default.asp?xcid=1799). We have strong connections with the world-class Department of Nephrology and Transplantation Services (TQEH), where scientists regularly attend departmental meetings and many of the clinicians are heavily involved with research projects. We recently won a new NHMRC project grant beginning in 2009 and we have active collaborations with groups bringing expertise in vascular biology (Dr Claudine Bonder, Centre for Cancer Biology http://www.centreforcancerbiology.org.au/Bonder.htm) and cellular neuroscience (Dr Damien Keating, Flinders University http://som.flinders.edu.au/FUSA/NEUROSCIENCE/molecular.htm).

CURRENT PROJECTS IN THE LABORATORY

Gene therapy to prevent apoptosis in transplanted pancreatic islets

Apoptosis is the major cause of islet cell death post-transplantation. Anti-apoptotic factors, such as insulin-like growth factor II (IGF-II), have the potential to protect transplanted islets. This project involves transferring DNA encoding protective genes, such as IGF-II, to islet cells using an adeno-associated virus gene therapy vector. Function and viability of transduced islets will be evaluated using techniques such as ELISA, cytokine challenge and flow cytometry. Transduced islets will be assayed for in vivo function in a diabetic NOD-SCID model.

 

Role of zinc transporters in pancreatic islets:

Another limitation of islet transplantation is the damage that occurs during isolation due to mechanical and enzymatic stress. This leads to apoptosis and an insufficient number of cells to meet metabolic needs post-transplantation. Zinc plays a vital role in DNA replication, enzyme activity and cellular protection against apoptosis and oxidative stress. Zinc is very high in pancreatic beta cells (the cells that secrete insulin) and is important in synthesis, storage and release of insulin. We have shown that levels of zinc transporter molecules on the surface of islet beta cells vary greatly among diabetic and non-diabetic patients. Our aim is to measure the RNA and protein levels of various zinc transporters in isolated and cultured islets and correlate this with protection of insulin production. The importance of zinc transporters in vivo will be assessed using a diabetic mice model.

 

Endothelial progenitor cells to promote the success of pancreatic islet transplantation in the rat

The islets of the pancreas are one of the most heavily vascularised tissues in the body, requiring 10% of the pancreatic blood flow despite only making up 1% of the pancreatic mass. As such, islets become rapidly hypoxic (inadequate oxygen supply) following isolation. Endothelial progenitor cells (EPC) are multipotent cells that act as a circulating ‘repair kit’ for vasculature, assisting with the repair of endothelium and the growth of new vessels in hypoxic or damaged tissue. EPC may improve the revascularization and engraftment of isolated islets following transplantation. The aim of this project is to characterize EPC by flow cytometry using antibodies against cell surface markers (including VEGF receptor 2, CXCR4, CD146, VCAM-1, monocyte markers (CD14) and stem cell markers (CD133, CD34)) and a 3D tube-forming assay in Matrigel.The cells will be evaluated for their potential to improve revascularisation when cotransplanted with pancreatic islets in a rodent model of diabetes.

 

Tolerogenic dendritic cells for transplantation

Dendritic cells (DC) are the sentinels of the immune system, potently directing the immune response towards a reactive or tolerant outcome. As such, DC are vitally important following the transplantation of organs and tissues. Our group has a long history in working with DC. Current projects involve characterizing the DC subsets present in the draining lymph nodes following kidney and islet transplantation. Another aim involves genetically modifying DC to induce a tolerogenic phenotype, and coadministering these DC to prevent transplant rejection.

 

Files

• Transplantation Immunology Laboratory group, BHI 2009 - TIL.jpg [161.5K] (image/jpeg)
• Endothelial Progenitor Cell colony - RATepc.jpg [58.7K] (image/jpeg)

Entry last updated: Thursday, 3 Sep 2009