AG Pfirrmann (UbiCilia)
Research
AG Pfirrmann's research centers on two major cellular systems: the Ubiquitin Proteasome System (UPS) and primary cilia, with a focus on how these systems regulate and interact on critical cellular processes to maintain cellular and organismal health.
Ubiquitin Proteasome System (UPS) and the GID Complex: The UPS is a cellular quality control mechanism that targets proteins for degradation through tagging with ubiquitin, preparing them for their disposal. This system is vital for cellular survival, with conserved mechanisms across species. Among the UPS components, the GID complex, initially identified by Pfirrmann and colleagues in yeast, plays a key role in protein degradation. AG Pfirrmann's research has expanded to studying the GID complex's function in humans and model organisms, revealing that mutations in GID complex genes in C. elegans can extend lifespan by nearly a third likely by altering their metabolism These findings hint at potential therapeutic applications for metabolic conditions like obesity and type 2 diabetes by targeting GID complex functions.
Primary Cilia and Cellular Energy Homeostasis: The group’s second research focus is primary cilia, small, evolutionarily conserved organelles that serve as cellular antennae, detecting and processing external signals crucial for cellular function. Primary cilia play a role in maintaining cellular energy balance and protein homeostasis (proteostasis), interacting with the UPS and the GID complex. This link is of medical interest as dysfunctional primary cilia contribute to various hereditary diseases, known as ciliopathies, which affect approximately 1 in 2000 individuals. Understanding the interaction between primary cilia, the GID-complex, and ciliary proteostasis may offer insights into disease mechanisms and potential treatments.
Current Projects
Function of the GID Complex in the Regulation of Lifespan
This project explores the role of the GID complex in regulating the lifespan of organisms. Using C. elegans as a model system, we aim to understand how the GID complex impacts cellular and organismal aging. Key methodologies include life-span assays, advanced proteomics through DIA-based mass spectrometry, and GFP-based expression analyses. Our findings may uncover novel pathways influencing longevity and contribute to aging research.
Function of the GID Complex at the Primary Cilium
The GID complex is investigated for its role in maintaining the structure and function of the primary cilium. By studying the differences in transition zone protein localization between wild-type and Gid2 knock-out cell lines, we aim to identify substrates of the GID complex that play a role at the primary cilium.
The Regulation of Cell Death by the Primary Cilium
Primary cilia function as signalling hubs controlling cellular processes, such as cell division, cell migration, cell differentiation etc. Novel findings suggest an important role of primary cilia in the regulation of programmed cell death but the underlying mechanisms remain elusive. By using in vitro (murine and human cells) and in vivo (Xenopus laevis and mouse) models and by performing a series of cell and molecular biological methods (e.g. cell death and proximity ligation assays, CoIP analysis, immunofluorescence-based ciliary protein quantifications as well as small molecule- and RNAi-based rescue experiments), we aim to reveal how ciliary proteins govern programmed cell death. In the course of this project, we collaborate with the Schneider-Maunoury lab, Sorbonne University, Paris, the Walentek lab, Medical Center, University of Freiburg, the Saunier lab, Imagine Institute, Université Paris Cité and the Grune lab, German Institute of Human Nutrition Potsdam-Rehbrücke.
CiliAI: AI-Driven Analysis of Primary Cilia
In collaboration with Datamarkin, a French start-up, we have developed CiliAI, an innovative AI-based tool for automated detection and analysis of primary cilia in confocal microscopy images. This web-based platform streamlines data processing, enabling researchers to identify cilia and perform quantitative analyses with unprecedented efficiency. Hooray to Emrah Nazif the CEO to embark on this project.
Production of Polyclonal Antibodies for Gamma-Tubulin and Acetylated Tubulin
To advance research on primary cilia, we are producing high-quality polyclonal antibodies against gamma-tubulin and acetylated tubulin to allow triple stainings in confocal images. In collaboration with Preclinics in Potsdam, we have produced goat sera that will allow triple stainings for ciliary substructures. Thanks to Preclinics GmbH and Preclinics Certified Producs GmbH for joining this exciting project.
Group Members
Group leader: Prof. Dr. rer. nat. habil. Thorsten Pfirrmann
Thorsten Pfirrmann is a biochemist with a keen interest in intracellular protein degradation mechanisms. His academic journey began with studies in Technical Biology at the University of Stuttgart and the John Curtin School of Medical Research in Canberra, Australia. In 2002, he deepened his research activities in Professor Wolf's lab in Stuttgart, where he completed his doctorate. After earning his Ph.D., Pfirrmann continued his scientific career, undertaking postdoctoral studies starting in 2006 at the Karolinska Institute in Professor Masucci's lab, followed by research in Professor Ljungdahl's lab at Stockholm University. Since 2011, he is teaching biochemistry to medical students at Martin Luther University Halle-Wittenberg. In October 2020, Pfirrmann assumed a professorship in Biochemistry at the Health and Medical University in Potsdam. His research focuses particularly on the ubiquitin-proteasome system and its role in protein homeostasis, as well as on the function of primary cilia in cellular signal transduction.
E-Mail: thorsten.pfirrmann@hmu-potsdam.de | Online Profile: Researchgate
Show Thorsten Pfirrmann's publications
2024
- Liu, C., I.H. Hatzianestis, T. Pfirrmann, S.H. Reza, E.A. Minina, A. Moazzami, S. Stael, E. Gutierrez-Beltran, E. Pitsili, P. Dormann, S. D'Andrea, K. Gevaert, F. Romero-Campero, P. Ding, M.K. Nowack, F. Van Breusegem, J.D.G. Jones, P.V. Bozhkov, and P.N. Moschou, Seed longevity is controlled by metacaspases.Nat Commun, 2024. 15(1): p. 6748 DOI: 10.1038/s41467-024-50848-2.
2023
- Job, F., C. Mai, P. Villavicencio-Lorini, J. Herfurth, H. Neuhaus, K. Hoffmann, T. Pfirrmann, and T. Hollemann, OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development. Biochim Biophys Acta Gene Regul Mech, 2023. 1866(1): p. 194901 DOI: 10.1016/j.bbagrm.2022.194901.
- Pfirrmann, T., B. Franco, D. Kopinke, and C. Gerhardt, Editorial: Regulation of proteostasis and cellular energy homeostasis at the primary cilium. Front Cell Dev Biol, 2023. 11: p. 1285237 DOI: 10.3389/fcell.2023.1285237.
- Varshavsky, A., D. Finley, A.L. Goldberg, T.A. Rapoport, and T. Pfirrmann, Dieter Wolf (1941–2023): a life dedicated to understanding protein quality control and the ubiquitin‐proteasome system. 2023.
- Job, F., Mai, C., Villavicencio-Lorini, P., Herfurth, J., Neuhaus, H., Hoffmann, K., Pfirrmann, T., & Hollemann, T. (2023). OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development. Biochimica et biophysica acta. Gene regulatory mechanisms, 1866(1), 194901. https://doi.org/10.1016/j.bbagrm.2022.194901
- Liu, C., Hatzianestis, I. H., Pfirrmann, T., Reza, S. H., Minina, E. A., Moazzami, A., Stael, S., Gutierrez-Beltran, E., Pitsili, E., Dörmann, P., Andrea, S. D., Gevaert, K., Romero-Campero, F., Ding, P., Nowack, M. K., Breusegem, F. V., Jones, J. D. G., Bozhkov, P. V., & Moschou, P. N. (2023). Seed Longevity is Controlled by Metacaspases. bioRxiv, 2023.2003.2019.533321. https://doi.org/10.1101/2023.03.19.533321
- Varshavsky, A., Finley, D., Goldberg, A. L., Rapoport, T. A., & Pfirrmann, T. (2023). Dieter Wolf (1941-2023): a life dedicated to understanding protein quality control and the ubiquitin-proteasome system. Embo Journal, 42(11). https://doi.org/10.15252/embj.2023114222
2022
- Hantel, F., Liu, H., Fechtner, L., Neuhaus, H., Ding, J., Arlt, D., Walentek, P., Villavicencio-Lorini, P., Gerhardt, C., Hollemann, T., & Pfirrmann, T. (2022). Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components. Journal of cell science, 135(9), jcs259209. https://doi.org/10.1242/jcs.259209
- Kuldyushev, N., Schönherr, R., Coburger, I., Ahmed, M., Hussein, R. A., Wiesel, E., Godbole, A., Pfirrmann, T., Hoshi, T., & Heinemann, S. H. (2022). A GFP-based ratiometric sensor for cellular methionine oxidation. Talanta, 243, 123332. https://doi.org/10.1016/j.talanta.2022.123332
- Pfirrmann, T., & Gerhardt, C. (2022). Life-Saver or Undertaker: The Relationship between Primary Cilia and Cell Death in Vertebrate Embryonic Development. Journal of developmental biology, 10(4), 52. https://doi.org/10.3390/jdb10040052
- Gerhardt, C. & Pfirrmann, T. (2022). Extracellular vesicles in ciliary signaling. Trillium Extracellular Vesicles. https://doi.org/10.47184/tev.2022.01.07
2021
- Fechtner, L., & Pfirrmann, T. (2021). The GID ubiquitin ligase complex just reached the next level of complexity. Molecular cell, 81(11), 2270–2272. https://doi.org/10.1016/j.molcel.2021.05.003
- Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., … Tong, C. K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy, 17(1), 1–382. https://doi.org/10.1080/15548627.2020.1797280
- Pfirrmann, T., Chondrogianni, N., Olzscha, H., Vasilaki, A. Editorial: Dysregulated Protein Homeostasis in the Aging Organism. Front Mol Biosci. 2021 Oct 14;8:788118. https://doi.org/10.3389%2Ffmolb.2021.788118
- Pfirrmann, T., Franco, B., Kopinke, D., & Gerhardt, C. (2023). Editorial: Regulation of proteostasis and cellular energy homeostasis at the primary cilium. Frontiers in cell and developmental biology, 11, 1285237. https://doi.org/10.3389/fcell.2023.1285237
- Fechtner, L. and Pfirrmann, T. (2021) Ubiquitin Ligases Involved in Progeroid Syndromes and Age-Associated Pathologies. Proteostasis and Proteolysis. https://doi.org/10.1201/9781003048138
Dr. rer. nat. habil. Christoph Gerhardt (Principal Investigator)
Christoph Gerhardt is a senior scientist at the Health and Medical University (HMU) in Potsdam. His research focus lies on the function of the primary cilium and on analysing the molecular mechanisms underlying the development of ciliopathies, human diseases caused by ciliary dysfunction. Prior to his move to Potsdam in September 2021, he was head of the cilia research group at the Heinrich Heine University in Düsseldorf. His group made groundbreaking discoveries in the cilia research field, such as the description of a cilia-regulated proteasome and the detailed investigation of how the ciliary gate assembles in vertebrates. Gerhardt authored numerous publications on primary cilia and ciliary signalling (especially Hedgehog signalling). His special focus lies on RPGRIP1L, a ciliopathy protein on which Gerhardt is working since over twenty years.
E-Mail: christoph.gerhardt@hmu-potsdam.de | Online Profile: ResearchGate
Show Christoph Gerhardt's publications
2022
- Pfirrmann, T., & Gerhardt, C. (2022). Life-Saver or Undertaker: The Relationship between Primary Cilia and Cell Death in Vertebrate Embryonic Development. Journal of developmental biology, 10(4), 52. https://doi.org/10.3390/jdb10040052
- Gerhardt, C. & Pfirrmann, T. (2022). Extracellular vesicles in ciliary signaling. Trillium Extracellular Vesicles. https://doi.org/10.47184/tev.2022.01.07
- Hantel, F., Liu, H., Fechtner, L., Neuhaus, H., Ding, J., Arlt, D., Walentek, P., Villavicencio-Lorini, P., Gerhardt, C., Hollemann, T., & Pfirrmann, T. (2022). Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components. Journal of cell science, 135(9), jcs259209. https://doi.org/10.1242/jcs.259209
2021
- Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., … Tong, C. K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy, 17(1), 1–382. https://doi.org/10.1080/15548627.2020.1797280
- Pfirrmann, T., Franco, B., Kopinke, D., & Gerhardt, C. (2023). Editorial: Regulation of proteostasis and cellular energy homeostasis at the primary cilium. Frontiers in cell and developmental biology, 11, 1285237. https://doi.org/10.3389/fcell.2023.1285237
- Wiegering, A., Dildrop, R., Vesque, C., Khanna, H., Schneider-Maunoury, S., & Gerhardt, C. (2021). Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone. Molecular biology of the cell, 32(8), 675–689. https://doi.org/10.1091/mbc.E20-03-0190
2020
- Gerhardt C. (2020). A View on the Contribution of Hedgehog Signalling to Ventricular Septal Development. Journal of clinical cardiology, 1(1), 40-42. https://doi.org/10.33696/cardiology.1.005
2019
- Wiegering, A., Petzsch, P., Köhrer, K., Rüther, U., & Gerhardt, C. (2019). GLI3 repressor but not GLI3 activator is essential for mouse eye patterning and morphogenesis. Developmental biology, 450(2), 141–154. https://doi.org/10.1016/j.ydbio.2019.02.018
- Wiegering, A., Rüther, U., & Gerhardt, C. (2019). The Role of Primary Cilia in the Crosstalk between the Ubiquitin-Proteasome System and Autophagy. Cells, 8(3), 241. https://doi.org/10.3390/cells8030241
- Gerhardt C. (2019). Treatment of Ciliopathies: Current Perspectives. Current medicinal chemistry, 26(17), 3080. https://doi.org/10.2174/092986732617190820123648
2018
- Wiegering, A., Rüther, U., & Gerhardt, C. (2018). The ciliary protein Rpgrip1l in development and disease. Developmental biology, 442(1), 60–68. https://doi.org/10.1016/j.ydbio.2018.07.024
- Struchtrup, A., Wiegering, A., Stork, B., Rüther, U., & Gerhardt, C. (2018). The ciliary protein RPGRIP1L governs autophagy independently of its proteasome-regulating function at the ciliary base in mouse embryonic fibroblasts. Autophagy, 14(4), 567–583. https://doi.org/10.1080/15548627.2018.1429874
- Wiegering, A., Dildrop, R., Kalfhues, L., Spychala, A., Kuschel, S., Lier, J. M., Zobel, T., Dahmen, S., Leu, T., Struchtrup, A., Legendre, F., Vesque, C., Schneider-Maunoury, S., Saunier, S., Rüther, U., & Gerhardt, C. (2018). Cell type-specific regulation of ciliary transition zone assembly in vertebrates. The EMBO journal, 37(10), e97791. https://doi.org/10.15252/embj.201797791
2017
- Wiegering, A., Rüther, U., & Gerhardt, C. (2017). The Role of Hedgehog Signalling in the Formation of the Ventricular Septum. Journal of developmental biology, 5(4), 17. https://doi.org/10.3390/jdb5040017
2016
- Gerhardt, C., Wiegering, A., Leu, T., & Rüther, U. (2016). Control of Hedgehog Signalling by the Cilia-Regulated Proteasome. Journal of developmental biology, 4(3), 27. https://doi.org/10.3390/jdb4030027
- Gerhardt, C., Leu, T., Lier, J. M., & Rüther, U. (2016). The cilia-regulated proteasome and its role in the development of ciliopathies and cancer. Cilia, 5, 14. https://doi.org/10.1186/s13630-016-0035-3
2015
- Gerhardt, C., Lier, J. M., Burmühl, S., Struchtrup, A., Deutschmann, K., Vetter, M., Leu, T., Reeg, S., Grune, T., & Rüther, U. (2015). The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium. The Journal of cell biology, 210(1), 115–133. https://doi.org/10.1083/jcb.201408060
2013
- Gerhardt, C., Lier, J. M., Kuschel, S., & Rüther, U. (2013). The ciliary protein Ftm is required for ventricular wall and septal development. PloS one, 8(2), e57545. https://doi.org/10.1371/journal.pone.0057545
2011
- Besse, L., Neti, M., Anselme, I., Gerhardt, C., Rüther, U., Laclef, C., & Schneider-Maunoury, S. (2011). Primary cilia control telencephalic patterning and morphogenesis via Gli3 proteolytic processing. Development (Cambridge, England), 138(10), 2079–2088. https://doi.org/10.1242/dev.059808
2007
- Delous, M., Baala, L., Salomon, R., Laclef, C., Vierkotten, J., Tory, K., Golzio, C., Lacoste, T., Besse, L., Ozilou, C., Moutkine, I., Hellman, N. E., Anselme, I., Silbermann, F., Vesque, C., Gerhardt, C., Rattenberry, E., Wolf, M. T., Gubler, M. C., Martinovic, J., … Saunier, S. (2007). The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nature genetics, 39(7), 875–881. https://doi.org/10.1038/ng2039
M.Sc. Eliza Karapetian (Phd candidate (rer. med.))
Eliza Karapetian is a doctoral candidate and Thorsten’s alumni Bachelor student. Her research focuses on the function of the GID complex at the primary cilium, her enthusiastic research efforts pursue the discovery of novel GID complex substrates at the primary cilium.
E-Mail: eliza.karapetian@hmu-potsdam.de
Show Eliza Karapetian's publications
2022
- Toma, G., Karapetian, E., Massa, C., Quandt, D., & Seliger, B. (2022). Characterization of the effect of histone deacetylation inhibitors on CD8+ T cells in the context of aging. Journal of translational medicine, 20(1), 539.
- Toma, G., Lemnian, I. M., Karapetian, E., Grosse, I., & Seliger, B. (2022). Transcriptional Analysis of Total CD8+ T Cells and CD8+CD45RA- Memory T Cells From Young and Old Healthy Blood Donors. Frontiers in immunology, 13, 806906. https://doi.org/10.3389/fimmu.2022.806906
B.Sc. Rakesh Sharma (M.Sc. candidate)
Rakesh Sharma is a Master student who came all the way from the Indian Institute of Science Education and Research, Mohali Punjab, India to follow up his research interest on metabolism and organismal aging using C. elegans as a model organism.
E-Mail: rakesh.sharma@hmu-potsdam.de
Cand. med. Wajahat Ahmad (Doctoral candidate (Dr. med.))
Wajahat Ahmad is a medical student at HMU and a doctoral candidate. He studies the impact of primary cilia on the insulin signalling pathway.
Cand. med. Arman Boyraz (Doctoral candidate (Dr. med.))
Arman Boyraz is a medical student at HMU and a doctoral candidate. He is interested in oxidative stress responses and loves to measure SOD activities.
Open Positions in the Pfirrmann Group
Starting date: immediately | Application deadline: none | Published: 01.04.2025
Medical PhD Students/M.Sc. Students (m/f/d)
at the Medical Faculty of the HMU Potsdam
We are always interested in motivated, ambitious and curious Master- and PhD-students interested in studying protein degradation and/or functions of the primary cilium.
Application
Send us a short e-mail about your research interest to thorsten.pfirrmann@hmu-potsdam.de
HMU, Professor Dr. Thorsten Pfirrmann, Schiffbauergasse Nr. 14, 14467 Potsdam