The Barker laboratory studies cell surface receptors and signaling pathways that regulate life and death decisions in the normal nervous system and in cancer. The goal of the lab is perform relevant and significant science that will benefit human health and to provide a superb training environmen...
The Barker laboratory studies cell surface receptors and signaling pathways that regulate life and death decisions in the normal nervous system and in cancer. The goal of the lab is perform relevant and significant science that will benefit human health and to provide a superb training environment for enthusiastic trainees who are keen to pursue a career in biomedical research.
One main area of interest in the Barker lab concerns a family of secreted factors called the neurotrophins. The four members of this family that are expressed in animals play crucial roles in the development and maintenance of the nervous system. One of the cell surface receptors for the neurotrophins that is termed the p75 neurotrophin receptor (or p75NTR) activates a form of cellular suicide known as apoptosis that is important for neuronal loss after injury. Interestingly, p75NTR is important for neuron growth process outgrowth as well as several other important functions.
p75NTR actions have been implicated in neuronal dysfunctions that range from Alzheimer’s disease to amyotrophic lateral sclerosis (ALS) to the irreversible damage that occurs after spinal cord damage. Understanding the molecular details of p75NTR function is a central goal of the Barker lab.
The Barker lab also studies a group of proteins termed the inhibitors of apoptosis (IAPs). The IAPs were initially characterized for their ability to block cell death but for most members of this family, the molecular mechanisms that regulate this function have remained obscure. Determining the cellular function of these proteins may be important for treating malignancies since IAPs are over-expressed in cancer and are widely believed to support cancer cell survival. The Barker lab is using a number of in vivo and in vitro model system to identify the physiological roles of the IAPs, to understand how they participate in signaling cascades in normal cells, and to determine how their function contributes to cancer progression.
The other main area that the lab focuses on revolves around the LGI family, a poorly characterized family of secreted proteins that have important roles in neuronal development and maintenance. LGI1 (for leucine-rich, glioma inactivated 1) was originally identified as a potential tumor suppressor but subsequent studies showed that mutations in LGI1 cause a type of epilepsy in humans. Precisely how LGI1 and related factors contribute to neuronal function remains unknown. The Barker lab has recently identified a cell surface receptor (termed NgR1) present on neurons that binds LGI1 and is now using a combination of biochemistry, physiology and genetics to determine how LGI1 activates cell surface receptors to signal to the interior of the cell.