AG Kramer
Research
The research group of Prof. Kramer investigates the molecular signal transduction pathways important during nervous system development and maintenance as well as alterations in these processes in neurodegenerative diseases such as Parkinson´s Disease (PD) or dementia which are characterized by loss of specific neuronal cells. Brain tissue of patients, genetically engineered mouse models as well as cultured and differentiated stem cells, primary cells and established cell lines are used to answer questions regarding protein expression, interaction and degradation. We make use of a large variety of state of the art molecular and cellular biology techniques such as immunohistochemistry and -fluorescence, (confocal) microscopy, stereology, Western blotting, PCR, qRT-PCR, Co-IP, viral infections, genetic alterations by CRISPR/Cas9 and transfections and many more.
One focus is the investigation of different signaling pathways of the glial cell line-derived neurotrophic factor (GDNF) such as the receptor tyrosine kinase RET, the neuronal cell adhesion molecule (NCAM), integrins and others in the midbrain dopaminergic system. Another focus is the analysis of protein homeostasis which is influenced by protein expression, folding, localization and degradation. Knowledge gained from these experiments helps to elucidate the molecular mechanisms leading to neurodegenerative diseases such as PD and dementia and paves the way to the development of novel therapeutic approaches against these devastating diseases.
Current Projects
The interplay of parkin and the receptor tyrosine kinase RET in Parkinson´s Disease (PD) and dementia with Lewy body (DLB) patients concerning cell survival, inflammasome activation and gliosis
This project aims to understand how and to which extent parkin might be able to prevent neurodegeneration in patients with PD or DLB. It has been shown that parkin can regulate cellular processes such as proteasomal degradation, oxidative and endoplasmic reticulum stress, mitochondrial integrity, autophagy/mitophagy, inflammasome inactivation and cell death. RET signaling in neurons has been found to stimulate cell survival, axon outgrowth and guidance, mitochondrial integrity and neurotransmitter release. Here, we want to investigate how parkin can act on RET’s protein expression, degradation and signaling on the cell surface. Moreover, we want to show how parkin and RET can cooperate to act on tissue inflammation, e.g. microglioses as well as the activation of the inflammasome and to which extent its sensor proteins NLRP3 and cleaved Caspase-1 are affected in the cortex and substantia nigra in healthy individuals and those with PD or DLB. To address these questions, we use cellular and molecular biology techniques (IHC, IF, PCR, qRT-PCR, WB, Co-IP, confocal microscopy), genetically engineered mouse models, human tissue, primary cells as well as established cell lines
The role of alternative glial cell line-derived neurotrophic factor (GDNF) receptors and signaling cascades in the midbrain dopaminergic system
This project aims to investigate the function of alternative receptors of GDNF in the dopaminergic system such as their effect on dopaminergic neuron survival and physiology. Here, genetically engineered mouse models are used to evaluate the function of integrin β1 (Int β1), integrin linked kinase (ILK), neuronal cell adhesion molecule (NCAM), and the canonical GDNF receptor RET. We investigate in the brains of these mice different histological parts of the dopaminergic system such as the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA) and the striatum, an important dopaminergic innervation region. To investigate the molecular mechanisms behind the histological phenotypes we are also culturing different cell lines studying their physiological processes with molecular biology methods (IHC, IF, PCR, qRT-PCR, WB, Co-IP, confocal microscopy). We are utilizing brain tissue from Parkinson’s disease and dementia with Lewy body patients to analyze disease related alterations of the GDNF receptor signaling cascades in their dopaminergic system.
Group Members
Group leader: Prof. Dr. rer. nat. habil. Edgar R. Kramer
Edgar Kramer studied Biology at the University Konstanz, Germany. He got his PhD in Biochemistry from the Institute for Molecular Pathology (IMP) in Vienna, Austria. He did a Postdoc at the EMBL (Heidelberg) and Max-Planck-Institute for Neurobiology (Martinsried/Munich). Edgar got his habilitations in Neurobiology (LMU, Munich) and Zoology (Centre for Molecular Neurobiology Hamburg). He is a full Professor at the University of Plymouth, England (since 2017). Since WS 2022/2023 he was also appointed to a full Professor for Physiology at the Health and Medical University Potsdam (HMU). His research group investigates molecular signal transduction pathways and processes involved in neuronal development as well as neurodegenerative disorders, such as Parkinson´s disease and dementia. The laboratory focuses on in vivo and in vitro experiments analyzing alterations in protein expression, protein-protein interactions and protein degradation. Techniques used in this context are transgenic mouse models, culturing and differentiating CRISPR- and transfection-modified stem cells and cell lines, immunohistochemistry and immunofluorescence, microscopy and stereology, Western blotting and in situ hybridizations, IP and co-IP, different forms of PCR, viral infections, and human tissue analysis.
E-Mail: edgar.kramer@hmu-potsdam.de | Online Profile: ResearchGate
Show Edgar Kramer's publications
2022
- Conway, J. A., & Kramer, E. R. (2022). Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic. Neural regeneration research, 17(7), 1462–1467. https://doi.org/10.4103/1673-5374.327330
- Chohan, M. O., Kopelman, J. M., Yueh, H., Fazlali, Z., Greene, N., Harris, A. Z., Balsam, P. D., Leonardo, E. D., Kramer, E. R., Veenstra-VanderWeele, J., & Ahmari, S. E. (2022). Developmental impact of glutamate transporter overexpression on dopaminergic neuron activity and stereotypic behavior. Molecular psychiatry, 27(3), 1515–1526. https://doi.org/10.1038/s41380-021-01424-3
- Conway, J. A., Kinsman, G., & Kramer, E. R. (2022). The Role of NEDD4 E3 Ubiquitin-Protein Ligases in Parkinson's Disease. Genes, 13(3), 513. https://doi.org/10.3390/genes13030513
2020
- Baaske, M. K., Kramer, E. R., Meka, D. P., Engler, G., Engel, A. K., & Moll, C. K. E. (2020). Parkin deficiency perturbs striatal circuit dynamics. Neurobiology of disease, 137, 104737. https://doi.org/10.1016/j.nbd.2020.104737
- Conway, J. A., Ince, S., Black, S., & Kramer, E. R. (2020). GDNF/RET signaling in dopamine neurons in vivo. Cell and tissue research, 382(1), 135–146. https://doi.org/10.1007/s00441-020-03268-9
2018
- Drinkut, A., Tillack, K., Meka, D. P., Schulz, J. B., Kügler, S., & Kramer, E. R. (2018). Correction to: Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model. Cell death & disease, 9(6), 634. https://doi.org/10.1038/s41419-018-0636-4
2016
- Friedemann, T., Ying, Y., Wang, W., Kramer, E. R., Schumacher, U., Fei, J., & Schröder, S. (2016). Neuroprotective Effect of Coptis chinensis in MPP[Formula: see text] and MPTP-Induced Parkinson's Disease Models. The American journal of Chinese medicine, 44(5), 907–925. https://doi.org/10.1142/S0192415X16500506
- Drinkut, A., Tillack, K., Meka, D. P., Schulz, J. B., Kügler, S., & Kramer, E. R. (2016). Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model. Cell death & disease, 7(9), e2359. https://doi.org/10.1038/cddis.2016.263
2015
- Kramer, E. R., & Liss, B. (2015). GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease. FEBS letters, 589(24 Pt A), 3760–3772. https://doi.org/10.1016/j.febslet.2015.11.006
- Meka, D. P., Müller-Rischart, A. K., Nidadavolu, P., Mohammadi, B., Motori, E., Ponna, S. K., Aboutalebi, H., Bassal, M., Annamneedi, A., Finckh, B., Miesbauer, M., Rotermund, N., Lohr, C., Tatzelt, J., Winklhofer, K. F., & Kramer, E. R. (2015). Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. The Journal of clinical investigation, 125(5), 1873–1885. https://doi.org/10.1172/JCI79300
- Kramer E. R. (2015). Crosstalk of parkin and Ret in dopaminergic neurons. Oncotarget, 6(18), 15704–15705. https://doi.org/10.18632/oncotarget.4465
- Kramer E. R. (2015). The neuroprotective and regenerative potential of parkin and GDNF/Ret signaling in the midbrain dopaminergic system. Neural regeneration research, 10(11), 1752–1753. https://doi.org/10.4103/1673-5374.165295
- Tillack, K., Aboutalebi, H., & Kramer, E. R. (2015). An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice. PloS one, 10(8), e0136203. https://doi.org/10.1371/journal.pone.0136203
2012
- Gonzalez-Reyes, L. E., Verbitsky, M., Blesa, J., Jackson-Lewis, V., Paredes, D., Tillack, K., Phani, S., Kramer, E. R., Przedborski, S., & Kottmann, A. H. (2012). Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit. Neuron, 75(2), 306–319. https://doi.org/10.1016/j.neuron.2012.05.018
2010
- Lücking, C. B., Lichtner, P., Kramer, E. R., Gieger, C., Illig, T., Dichgans, M., Berg, D., & Gasser, T. (2010). Polymorphisms in the receptor for GDNF (RET) are not associated with Parkinson's disease in Southern Germany. Neurobiology of aging, 31(1), 167–168. https://doi.org/10.1016/j.neurobiolaging.2008.03.006
- Aron, L., Klein, P., Pham, T. T., Kramer, E. R., Wurst, W., & Klein, R. (2010). Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS biology, 8(4), e1000349. https://doi.org/10.1371/journal.pbio.1000349
2008
- Mishra, A., Knerr, B., Paixão, S., Kramer, E. R., & Klein, R. (2008). The protein dendrite arborization and synapse maturation 1 (Dasm-1) is dispensable for dendrite arborization. Molecular and cellular biology, 28(8), 2782–2791. https://doi.org/10.1128/MCB.02102-07
- Deininger, K., Eder, M., Kramer, E. R., Zieglgänsberger, W., Dodt, H. U., Dornmair, K., Colicelli, J., & Klein, R. (2008). The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 12539–12544. https://doi.org/10.1073/pnas.0801174105
2007
- Kowsky, S., Pöppelmeyer, C., Kramer, E. R., Falkenburger, B. H., Kruse, A., Klein, R., & Schulz, J. B. (2007). RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals. Proceedings of the National Academy of Sciences of the United States of America, 104(50), 20049–20054. https://doi.org/10.1073/pnas.0706177104
- Kramer, E. R., Aron, L., Ramakers, G. M., Seitz, S., Zhuang, X., Beyer, K., Smidt, M. P., & Klein, R. (2007). Absence of Ret signaling in mice causes progressive and late degeneration of the nigrostriatal system. PLoS biology, 5(3), e39. https://doi.org/10.1371/journal.pbio.0050039
2006
- Kramer, E. R., Knott, L., Su, F., Dessaud, E., Krull, C. E., Helmbacher, F., & Klein, R. (2006). Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb. Neuron, 50(1), 35–47. https://doi.org/10.1016/j.neuron.2006.02.020
2001
- Sørensen, C. S., Lukas, C., Kramer, E. R., Peters, J. M., Bartek, J., & Lukas, J. (2001). A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression. Molecular and cellular biology, 21(11), 3692–3703. https://doi.org/10.1128/MCB.21.11.3692-3703.2001
- Reimann, J. D., Freed, E., Hsu, J. Y., Kramer, E. R., Peters, J. M., & Jackson, P. K. (2001). Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell, 105(5), 645–655. https://doi.org/10.1016/s0092-8674(01)00361-0
- Geley, S., Kramer, E., Gieffers, C., Gannon, J., Peters, J. M., & Hunt, T. (2001). Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. The Journal of cell biology, 153(1), 137–148. https://doi.org/10.1083/jcb.153.1.137
2000
- Kramer, E. R., Scheuringer, N., Podtelejnikov, A. V., Mann, M., & Peters, J. M. (2000). Mitotic regulation of the APC activator proteins CDC20 and CDH1. Molecular biology of the cell, 11(5), 1555–1569. https://doi.org/10.1091/mbc.11.5.1555
- Sorensen, C. S., Lukas, C., Kramer, E. R., Peters, J. M., Bartek, J., & Lukas, J. (2000). Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis. Molecular and cellular biology, 20(20), 7613–7623. https://doi.org/10.1128/MCB.20.20.7613-7623.2000
- Petersen, B. O., Wagener, C., Marinoni, F., Kramer, E. R., Melixetian, M., Lazzerini Denchi, E., Gieffers, C., Matteucci, C., Peters, J. M., & Helin, K. (2000). Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1. Genes & development, 14(18), 2330–2343. https://doi.org/10.1101/gad.832500
1999
- Lukas, C., Sørensen, C. S., Kramer, E., Santoni-Rugiu, E., Lindeneg, C., Peters, J. M., Bartek, J., & Lukas, J. (1999). Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Nature, 401(6755), 815–818. https://doi.org/10.1038/44611
- Gieffers, C., Peters, B. H., Kramer, E. R., Dotti, C. G., & Peters, J. M. (1999). Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Proceedings of the National Academy of Sciences of the United States of America, 96(20), 11317–11322. https://doi.org/10.1073/pnas.96.20.11317
1998
- Kramer, E. R., Gieffers, C., Hölzl, G., Hengstschläger, M., & Peters, J. M. (1998). Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Current biology : CB, 8(22), 1207–1210. https://doi.org/10.1016/s0960-9822(07)00510-6
Open Positions in the Kramer Group
Starting date: immediately | Application deadline: none | Published: 17.02.2025
Postdoc/Academic Researcher (f,m,d) in Neurophysiology
at the Medical Faculty of the HMU Potsdam
We are recruiting a neuroscientist for a permanent full-time research and teaching position in the group of Professor Kramer.
Your Duties
- Research in the field of neurosciences especially concerning neurodegenerative diseases such as Parkinson‘s disease and dementia
- Writing and submitting grant applications for third-party research funding
- Teaching physiology/neurophysiology to medical students in seminars and practicals
- Mentoring and examining medical students
Qualification Profile
- Completed a medicine or natural sciences study with a PhD or doctoral degree
- Experienced and excited about neuroscience research, especially concerning neurodegenerative diseases
- Experienced in teaching medical students in physiology/neurophysiology
We offer
- Fulltime, permanent position
- 30 days of vacation per year
- Public transportation job ticket reduction
- Additional benefits concerning health insurance and retirement money
- A young and dynamic team and environment
- Personal development opportunities
Application
If you feel prepared for this exciting position please get in touch with us and send your application electronically to edgar.kramer@hmu-potsdam.de
HMU, Neurophysiology, Professor Dr. Edgar Kramer, Schiffbauergasse Nr. 14, 14467 Potsdam
Starting date: immediately | Application deadline: none | Published: 03.02.2025
Medical PhD Students (m/f/d)
at the Medical Faculty of the HMU Potsdam
Are you a HMU medical student interested in doing a wet lab medical thesis in neuroscience? Feel free to get in contact with us.
We warmly welcome applications from HMU medical students. An intrinsic interest to better understand complex neuroscience problems is mandatory, lab experience is desired but not needed. Self-founded applicants are welcome to apply.
Application
Send us a short e-mail about your research interest and background to edgar.kramer@hmu-potsdam.de.
HMU, Neurophysiology, Professor Dr. Edgar Kramer, Schiffbauergasse Nr. 14, 14467 Potsdam