Research in Hub 4 strives to go beyond the “beta amyloid hypothesis” of Alzheimer’s disease (AD) to address other factors contributing to AD and related forms of dementia. There are two major goals: 1) use interdisciplinary approaches to gain insight into disease mechanisms and develop treatments for dementia-related proteinopathies; 2) understand the relationship between altered metabolism and dementia symptom onset and disease severity. The research is driven by a multi-disciplinary team that includes experts in chemistry, pharmacology, pharmaceutical sciences, nutritional sciences, molecular biology and genetics, animal behaviors, clinical research, and patient care.
(all meetings are from 1:00 pm until 3:30 pm in the Life Sciences Library)
May 10, 2017 – Geoff Murphy’s Lab
July 12, 2017 – Ayyalusamy Ramamoorthy’s Lab
September 13, 2017 – Brandon Ruotolo’s Lab
November 8, 2017 – Anna Schwendeman’s Lab
Geoffrey Murphy is an Associate Professor in the Department of Molecular and Integrative Physiology and an Associate Research Professor in the Molecular and Behavioral Neuroscience institute. The Murphy lab is interested in neurological disease states including Alzheimer’s disease and temporal lobe epilepsy. In addition the lab is investigating the neural substrates that underlie complex psychiatric diseases such as bipolar.
Bing Ye is the Burton L. Baker Collegiate Professor of the Life Sciences and an associate professor of cell and developmental Biology. His laboratory studies how neuronal development contributes to the assembly and function of nervous systems and how defects in this process lead to diseases. The Ye lab collaborates with chemists and pharmaceutical scientists to develop therapeutic strategies for brain disorders.
Ayyalusamy (Rams) Ramamoorthy
Ayyalusamy (Rams) Ramamoorthy is the Robert W. Parry Collegiate Professor of Chemistry and Biophysics. His laboratory investigates the misfolding, aggregation and toxicity of amyloid peptides implicated in aging-related diseases. Specific focus is on high-resolution structural insights, role of lipid membrane, and development of small molecules to modulate amyloid aggregation.
Magdalena Ivanova is a Research Assistant Professor in the Department of Neurology and Adjunct Assistant Professor in the Program of Biophysics. Her laboratory applies biophysical and biochemical based approaches to study protein misfolding and aggregation in association with neurodegenerative diseases. The ultimate goal is to exploit the acquired information for developing therapies that may slow, delay, inhibit, or reverse neurodegeneration.
The Brandon Ruotolo group seeks to enable breakthroughs in structural biology and drug discovery by leveraging the potential of ion mobility-mass spectrometry (IM-MS) for the comprehensive, 3D structural analysis of the proteome. To this end, Ruotolo and his team have studied the role of solvation on biomolecular structure, introduced collision induced unfolding (CIU) – a new fingerprinting technology capable of detecting the structural state of protein-ligand complexes and biotherapeutics, developed software packages for the enhanced interpretation and throughput of IM-MS and CIU data, and investigated the structural consequences of small molecule drug-like compounds upon binding amyloid peptides.
Hank Paulson’s laboratory seeks to understand the mechanisms underlying neurodegenerative proteinopathies including polyglutamine diseases, frontotemporal dementia and Alzheimer’s disease. We use approaches ranging from in vitro analysis of recombinant proteins to mouse models of disease. Two major areas of focus are the polyglutamine disorder Spinocerebellar Ataxia type III (SCA3) and the Ubiquilin family of proteins implicated in numerous forms of neurodegeneration. In translational studies, we have identified compounds and developed gene silencing strategies that decrease levels of the toxic jean product in SCA3. In addition to co-directing the PFD Initiative, I direct the NIH-funded Alzheimer’s Disease Center at the University of Michigan.
Lisa Sharkey’s research interests focus on the consequences of protein mis-folding in neurodegenerative disease. She primarily studies Ubiquillin2, a quality control protein which when mutated causes a spectrum of human neurodegenerative disease including ALS and ALS/FTLD. In addition, she is investigating the effects of protein homeostasis on brain health and cognitive aging.
Peter Tessier is the Albert M. Mattocks Professor of Pharmaceutical Sciences, Chemical Engineering and Biomedical Engineering. His lab aims to develop next generation technologies for designing, discovering, engineering, characterizing, formulating and delivering biologics ranging from small affinity peptides to large monoclonal antibodies for molecular imaging, diagnostic and therapeutic applications. The Tessier lab is particularly interested in generating conformational antibodies that are selective for different types of soluble and insoluble aggregates linked to Alzheimer’s, Parkinson’s and other neurodegenerative diseases.
Anna Schwendeman is an Assistant Professor of Pharmaceutical Sciences. Her laboratory used designs synthetic lipoproteins for treatment of cardiovascular and neurologic disorders.