The Douglas Jefferson Lab

Research Publications Cell Biology Physiology

 

Identifying Glioblastoma Stem Cells

In collaboration with Brent Cochran, we are working on the detection and possible treatment of glioblastomas. Glioblastoma is a brain tumor; patients with glioblastoma have a median survival of 14 months. Even after successful surgical resection of the bulk of the tumor followed by radiation and chemotherapy, almost all glioblastomas recur. Recently, glioblastoma stem cells have been proposed to be the origin of glioblastomas. These tumor stem cells have the properties of normal adult stem cells but are also capable of initiating tumors in experimental models. We have been successful in culturing these stem cells from tumors resected at surgery. We have made a bank of monoclonal antibodies specific to glioblastoma stem cells and are in the process of screening these antibodies against pathology specimens and patient sera to determine whether there is one or more glioblastoma stem cell marker(s) that can be used for early detection and possibly treatment of human glioblastoma. 

Cystic Fibrosis and Liver Disease 

Cystic Fibrosis (CF)-related hepatobiliary disease is seen in ~20-30% of the CF patients, and is the second leading cause of death in this population. CF is a genetic disease mainly of the airway but it also involves other tissues. The CF‐affected tissue that my studies focus on is the liver. In the normal liver, only epithelial cells that line bile ducts express the cystic fibrosis transmembrane conductance regulator protein (CFTR. It is the absence of CFTR in the plasma membrane of cells that causes the CF phenotype. It is thought that CF associated fibrotic liver disease is due to inflammation caused by blockage of bile ducts. We hypothesize that this bile duct blockage is due to the reduced function of the bicarbonate/chloride anion transporter (Cl/HCO3exchanger). The Cl/HCO3 exchanger plays an important role in pH regulation of the bile by secreting HCO3into the lumen of the bile duct. Bile components like bile acids precipitate when the bile is not alkaline and could cause blockage of the bile ducts. Our goal is to determine the mechanism(s) by which the lack of CFTR in the plasma membrane causes dysfunction of the Cl/HCO3 exchanger.

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