ERI scientists are focusing their research efforts on a number of very serious and common medical disorders.
A major research focus at the ERI is studying how brain cells (neurons) function normally and how they may be altered in common, severe neurologic disorders such as Alzheimer's disease and Parkinson's disease. By understanding normal and abnormal function, new therapeutic strategies may be developed. Dr. Daniel Linseman studies the molecular mechanisms by which neurons die in various neurodegenerative disorders. In addition, he has developed a mouse model of Parkinson's disease and amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) to study the mechanisms of neuronal death. Dr. Martin Margittai is studying how aggregates of the protein tau evolve and their role in the development of neurodegenerative diseases. A molecular understanding of the folding properties of tau, its cellular interactions, and structural transitions are important prerequisites for the design of new drugs that intervene in the assembly process of this protein. Dr. Sean Shaheen is studying protein-protein interactions involved with various pathways leading to neurodegenerative diseases. He is also investigating how nanoparticles introduced into a protein's environment can alter its function. Using bioinformatics, he hopes to uncover correlations in protein sequences that may reveal the functions of certain proteins. Dr. Nancy Lorenzon is studying how calcium channels (which move calcium into and out of cells) and their genetic control may cause a number of nerve and muscle diseases with the hope of developing new therapeutic approaches for these disorders.
All patients with Alzheimer's disease have an increased production of amyloidogenic fragments in their brains which are formed from a protein known as Amyloid Precursor Protein (APP). A protein fragment derived from APP known as Abeta has many toxic functions and can lead to the death of brain cells potentially reproducing the symptoms of Alzheimer's disease. Dr. Coughlan's research is focused on why and how Abeta increases in brain cells and how the hormone leptin affects this accumulation. In addition, she is working with Dr. Shaheen to design therapeutic approaches to remove this toxic peptide once it is made. Dr. David Patterson is studying a mouse model that develops brain changes and learning and memory alterations that resemble those in individuals with Alzheimer's disease. Since individuals with Down syndrome appear to have an increased risk for developing Alzheimer's disease, Dr. Patterson's research is also focusing on the complex interrelationships between these two disorders with the hope of developing therapies which may benefit both.
Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig's Disease)
ALS is a fatal disease caused by progressive death of motor neurons. Dr. Patrick Bosque is investigating the role of misfolded and aggregated proteins in ALS. Drs. Phillip Danielson, James Fogleman, and Catherine Kunst are studying the genetic basis (in a mouse model) for ALS. To date, they have identified certain protective genes. Identification of modifier genes and characterization of their mechanisms of action may lead to new targets of pharmacological intervention for ALS.
Diabetes and other metabolic disorders
Dr. Joseph Angleson studies the fundamental cellular and molecular mechanisms that regulate hormone secretion from the alpha and beta cells in the pancreas. In addition, he is investigating the mechanisms of signaling and secretion responsible for hormone release from the pituitary gland. Dr. Patterson is studying how folic acid supplementation, which is currently required in the United States because it reduces the frequency of serious birth defects, may increase the risk of breast, colorectal, and prostate cancer in older individuals.
Individuals with Down syndrome have a decreased risk of developing certain cancers, including breast cancer. Dr. Patterson has identified a gene in Down syndrome that may play a role in this reduced risk, and he is currently developing mouse models to study this observation. These studies may illuminate the process of breast cancer development and progression and lead, potentially, to new treatments for breast cancer. Dr. Patterson's laboratory is also investigating how folic acid supplementation may lead to development of various cancers.
Dr. Patterson's laboratory is studying how alterations in brain proteins in a mouse model of Down syndrome may produce the various intellectual disabilities seen in this disorder. The studies are aimed at developing new therapies. The relationship between Down syndrome and Alzheimer's disease is also being studied in a mouse model as well as the mechanism for the decreased risk of breast cancer in patients with Down syndrome.
Dr. Patterson's laboratory is creating a mouse model of an untreatable inborn error of metabolism that causes profound developmental delay often accompanied by autistic features observed in humans. These studies include detailed analysis of changes in brain chemistry with the hope of developing mechanisms to reverse these abnormalities. Drs. Patterson and Shaheen are collaborating to understand the basis for this disorder.