We are investigating Histone deacetylases (HDAC) which are part of an epigenetic regulatory system serving as a unique control of the chromatin remodeling process, determining the transcriptional availability of any given gene. HDAC inhibitors (HDACi) are reported to suppress neovascularization in various mouse models and have become a novel target for the epigenetic regulation of critical pathways in neurodegenerative diseases including AMD. Heterogeneous effects of HDAC function occur depending on the target locus and the tissue type as HDACi can trigger both pro- and anti-inflammatory effects in a range of inflammation-relevant cell types. These effects include changes in pro- inflammatory eotaxin expression. We aim to establish the effects of broad band chemical HDACi on eotaxin expression and the correlation to cell death.
We further use targeted inhibition of specific HDACs to define drivers of eotaxin expression as currently specificity of chemical HDAC is limited. We also are interested in establishing downstream effects of specific HDAC inhibition utilizing massive parallel RNA sequencing and taqman arrays and thereby gathering information about the major pathways affected by the specific HDAC inhibition involved in promoting cytokine expression. Our work aims to illuminate the usability of specific HDAC inhibition as a treatment of AMD.
Education 2012 – Current: Research Fellow at the University of Kentucky 2008-2011: Research Fellow for Queens University in Belfast (United Kingdom) 2006-2007: Research assistant at the Roskamp Institute (Sarasota, Florida) 1995-2002: “Diplom” in Biology (similar to Master’s degree) 1993-1995: “Vordiplom” in Biology (similar to Bachelor of Science)
I did my Ph.D thesis at the University of Leipzig, Germany, in the field of neurodegeneration, particularly Alzheimer’s Disease (AD). I studied protein glycation which is a non-enzymatic modification of proteins by reducing sugars or sugar fission products. After rearrangements, the initial reversible amadori product leads to formation of Advanced Glycation End products (AGEs). In these studies, I was revealing the most accessible proteins for glycation in neuronal cell lines by a proteomic approach. By combining two dimensional Gelelectrophoreses, immuno-cytochemistry and mass-spectrometry, I pointed out that tubulin and actin to be glycated as well as Cyclophiline A (an cis-trans-isomerase like Pin1) which can be related to neurodegenerative processes in AD. In order to address this evidence further, I modified key proteins in Alzheimer’s Disease by in-vitro glycation in a specific manner to reduce the variation of end structures to a minimum. This allowed me to calculate the mass-value added to a potentially modified peptides to predict and pinpoint mass-shifts in the spectra of the glycated protein samples, which were absent in the controls. With this approach I showed actual localisations of glycation-sides on key proteins in Alzheimer’s disease. My thesis work was founded and sponsored by “Deutsche Alzheimer Stiftung” (German Alzheimer’s Foundation) and European Union appropriations. My work lead to the publication of the paper titled Identification of AGE-modified Proteins in SH-SY5Y and OLN-93 Cells (Langer AK , Poon HF, Münch G, Lynn BC, Arendt T, Butterfield DA. Neurotoxicity Research, 2006, Vol. 9(4). pp. 255-268).
I continued on this work with a post-doctoral position at Queens University Belfast, working on the role of the Glyoxalse system in prevention of advanced glycation endproducts (AGE) in a diabetic rat model and Müller cells exposed to different glucose levels. The Glyoxalase system detoxifies the highly reactive alpha-oxoaldehydes methyglyoxal and glyoxal to lactate. Both oxoaldehydes are side products of various energy metabolisms. Especially under hyperglyceamic conditions (diabetes), alpha-oxoaldehydes occur in elevated concentrations. If not detoxified by the Glyoxalase system, they modify proteins, lipids and oligonucleotides, leading to Advanced Glycation Endproducts, potentially making the modified molecules dysfunctional. Our goal was to over-express Glyoxalase-1 (GLO-1) in our model systems to investigate if elevated (GLO-1) levels can help to lower the AGE burdon in diabetic animals and/or Müller cells under hyperglycemia. This data has been published in Diabetologica (Diabetologia. 2012 Mar;55(3):845-54.).
Hometown: Born in Wittmund (northern Germany)
Interests outside academia: Collecting vinyl records, Windsurfing, cycling, rollerblading, cinema/movies, travelling, flying remote controlled helicopters.