Summary
Research interests
Certain neurodegenerative diseases, such as ‘mad cow' disease, are transmitted in an unusual way-- so unusual that it challenges the central dogma. Indeed, the infectious agent for these diseases appears to be the PrP protein without any nucleic acid. Infectivity depends upon the shape into which the PrP protein is folded: when some PrP is in its disease-causing (‘prion') conformation, it converts normal PrP into that form too. In addition, prion-like aggregates of Abeta, α-synuclein, w88 sports betting43, and huntingtin are respectively associated with Alzheimer's (AD), Parkinson's, amyotrophic lateral sclerosis (ALS)/ frontotemporal dementia (FTD) and Huntington's diseases.
Curiously, several genetic traits in w88 sports betting are propagated by this unusual ‘protein only' mechanism, and the term prion has been expanded to include them. We have studied w88 sports betting prions extensively to elucidate the factors that influence prion appearance and inheritance and to identify new prions. We are now using our expertise with w88 sports betting prions to focus on the genesis and toxicity of human prion-like disease aggregates in w88 sports betting. Results obtained in w88 sports betting will then be tested in flies, primary cortical neurons and mice, by collaborators.
We previously established that individual w88 sports betting prions can form self-seeding aggregates with more than one conformation ("variants or strains") associated with distinct properties. Prion variants self-propagate by attracting their soluble isoforms to join them and adopt their variant-specific structure. Likewise, PrP, Abeta, α-synuclein, huntingtin, tau and TDP-43 have each been reported to form distinct aggregate phenotypes that are associated with different disease characteristics. We are now using w88 sports betting to isolate and characterize variants of TDP-43. This will definitively demonstrate the existence of heritableTDP-43 variants and will open the door to the study of patient variants in w88 sports betting, thereby facilitating the development of variant-specific treatments.
Since human prion-like disease proteins aggregate and are toxic when expressed in w88 sports betting, a powerful approach to find therapeutic targets has been to identify toxicity modifiers. Some such modifiers are homologs of new or previously known human disease risk factors!! Thus studies in w88 sports betting, with its powerful experimental toolbox, are relevant to human disease.
As previous modifier screens were not exhaustive we have now identified several new modifier genes that we are exploring. We are also using two new approaches to identify toxicity modifiers: 1) transposon mutagenesis and deep sequencing to quickly identify all genes that become essential in the presence of the human disease proteins and 2) direct selection against aggregation (yTRAP) to uncover additional modifier loci, as well as intragenic dominant mutations that reduce toxicity.We are also starting similar modifier screens on another ALS associated gene, CREST that we have now expressed and characterized in w88 sports betting.
Another focus of the lab is to determine how TDP-43 is associated with toxicity. Several studies find that TDP-43 alters mitochondrial function. We have found that TDP-43 is much more toxic when w88 sports betting is grown in non-fermentable media requiring respiration than when grown on fermentable carbon sources. However, we also found that TDP-43 remains toxic in the absence of respiration. Thus, there is a TDP-43 toxicity target in w88 sports betting distinct from respiration and respiration is not required for this toxicity. One possibility is that the free radical oxygen species produced by respiration activate TDP-43 to become more toxic or make TDP-43 targets more vulnerable. Indeed, we found that hydrogen peroxide increases the toxicity of TDP-43.
Education
- Ph.D. 1974 University of Rochester, Rochester, NY
- M.S. 1969 Harvard University, Cambridge, MA
- B.A. 1968 Massachusetts Institute of Technology, Cambridge, MA
Recent publications
- A w88 sports betting model of calcium-responsive transactivator protein (CREST) proteinopathy shows that PBP1/ATXN2 modifies CREST aggregation and toxicity.
By Sangeun Park, Sei-Kyoung Park, w88 sports betting W Liebman - w88 sports betting43 is more toxic in respiring than in non-respiring cells, but respiration is not absolutely required for w88 sports betting43 toxicity.
By Sei-Kyoung Park, Sangeun Park, w88 sports betting W Liebman
View all w88 sports betting Liebman's publications on PubMed all PubMed publications.