Many devastating human diseases arise from the accumulation of unfolded and aggregated proteins including amyotrophic lateral sclerosis (ALS), AD, HD and PD. How unfolded proteins, either as soluble or aggregated species, cause disease remains poorly understood, and multiple mechanisms are likely involved.
Existing therapeutic strategies include dissolving already-formed oligomers or aggregates and preventing protein aggregation by enhancing early steps of protein folding or degradation. Here we propose new strategies based on the hypothesis that up-regulation of vesicular trafficking pathways, lysosomal function and/or autophagy can clear cells of toxic proteins.
We will take advantage of our extensive, complementary expertise in the molecular mechanisms of membrane transport to develop these novel approaches to therapy.
Lois S. WeismanLois S. Weisman is the Sarah Winans Newman Professor of Cell and Developmental Biology and Research Professor in the Life Sciences Institute. Studies in her lab focus on baker’s yeast. The hope is that understanding how a single-celled organism functions will likely provide key insights into control of more complicated cells such as neurons, and will ultimately provide new information about animal physiology.
Daniel J. KlionskyDaniel J. Klionsky is the Alexander G. Ruthven Professor of Life Sciences. His laboratory uses yeast to study basic cellular processes including autophagy and organelle biogenesis.
Sami BarmadaSami Barmada is the Angela Dobson and Lyndon Welch Research Professor of Neurology and an assistant professor of neurology. His laboratory investigates RNA and protein metabolism in primary neurons and human stem cell-derived neurons, how deficiencies in these pathways lead to neurodegeneration in ALS and FTD, and how these pathways can be modified to prevent neuron loss.
Mara DuncanMara Duncan is an Assistant Professor in the Department of Cell and Developmental Biology. Her laboratory uses cellular models to study the fundamental mechanisms and identify new genes important for destroying proteins that may contribute to neurodegeneration.
Yanzhuang WangYanzhuang Wang is a Professor of the Department of Molecular, Cellular and Developmental Biology (MCDB) and Department of Neurology; he also serves as the Associate Chair for Research and Facilities of MCDB. His research focuses on the biogenesis, function, and defects of the Golgi in diseases such as Alzheimer’s disease and cancer.
Catherine Collins is an Assistant Professor of the Department of Molecular, Cellular and Developmental Biology . Her research is interested in the cellular mechanisms that neurons use to alter synaptic structure in response to environmental and developmental cues. Of particular interest is the cell biology of signaling within axons, which connect neurons to distant parts of the brain and body.
William DauerWilliam Dauer’s laboratory seeks to unravel the molecular and cellular mechanisms of diseases that disrupt the motor system. In exploring these diseases, we are also interested in understanding a fundamental question relevant to CNS disease generally: what factors determine the selective vulnerability of particular cell types or circuits to particular insults? Our primary focus is on Parkinson’s disease and primary dystonia. We have a specific focus on nuclear membrane-localized events that are implicated in neurodegenerative and neurodevelopmental disease. Our efforts typically center on human disease genes, employing a range of molecular, cellular, and whole animal studies to dissect the normal role of disease proteins, and how pathogenic mutations lead to disease. In addition to my laboratory efforts, I direct the Morris K. Udall Center of Excellence for Parkinson’s Disease Research and the University of Michigan Movement Disorders Group.
Philip Andrews is a Professor in Computational Medicine and Bioinformatics and Biological Chemistry. His laboratory is very interested in understanding the functional and organizational patterns underlying complex systems with our major emphasis being on protein interactions and the role of post-translational modifications in controlling those interactions. They rely primarily on mass spectrometry and protein chemistry techniques to address problems in these areas.
Haoxing Xu is a professor in the Department of Molecular, Cellular and Developmental Biology. His laboratory is interested in understanding the physiological and pathological functions of Transient Receptor Potential (TRP) ion channels, lysosome ion channels, and Ca2+ signaling.