1. Mechanisms and repair of brain injury associated with premature birth.

Brain injury, ranging from mild to severe cognitive deficits and cerebral palsy are associated with premature birth and result in significant suffering to the afflicted and their families and is a major financial burden to society.   As epidemiological studies indicate that a likely cause for these conditions is maternal infection, the laboratory has established a new mouse model which recapitulates the disease.  The studies, which are funded by NINDS, are beginning to define the molecular and cellular events that lead to neurological deficits, and are expected to reveal new strategies that will allow the development of both predictors that help identify infants at risk and therapeutic agents reduce the consequences in afflicted children.

2. Novel immune-based approaches to eliminate brain tumors.

Our understanding of how the immune system initially provides protection against brain tumors and, conversely, how it later fails and eventually promotes tumor progression in the so-called immunoprivileged environment of the brain is relatively meager.  Orthotopic syngeneic graft models have been used to study this, but are hampered by the fact that implanted cells lack normal tumor stroma, derive from tumors that have already learned to avoid immunoeradication, are altered by long-term culture, and have surpassed the stepwise genetic changes that occur in human tumors. Moreover, the immune-brain barrier (blood brain barrier) is breached at the outset of implantation by the injection procedure, artificially creating both an injury inflammatory response and an entry site for immune cells.  In studies funded by the National Brain Tumor Foundation, the laboratory is currently using genetically-engineered mice that develop spontaneous brain tumors to determine mechanisms by which the natural immune response changes as tumors progress from early to later stages, and how the immune system can be manipulated to eliminate tumors.

3. Parkinson’s Disease.

Recent genetic findings suggest that an abnormal inflammatory response and/or an overly-active immune system may underlie or predispose individuals to Parkinson Disease.  Moreover anatomical findings in Parkinson's patients and epidemiological data on anti-inflammatory drug use suggest that inflammation may play a deleterious role in disease progression.   In collaboration with Dr. Marie-Françoise Chesselet, the Waschek lab is using the pathology of Parkinson's-like Disease in α-synuclein transgenic mice or mice given the pesticide paraquat is accelerated in mice deficient in the neuropeptide PACAP.