Pharmakogenomik
Department für Experimentelle und Klinische Pharmakologie und Pharmakogenomik

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Adresse: Lothar-Meyer-Bau
Wilhelmstr. 56
72074 Tübingen

frontend.sr-only_#{element.icon}: 07071 29-73082

frontend.sr-only_#{element.icon}: 07071 29-35286

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Research AG Philipp

The research focus of our group is on the following topics:

Contact

Head of research group:

frontend.sr-only_#{element.contextual_1.children.icon}: Prof. Dr. Melanie Philipp

More about the person
  • Kinase Activity Is Not Required for G Protein-Coupled Receptor Kinase 4 Restraining mTOR Signaling during Cilia and Kidney Development. 
    Gerhards J, Maerz LD, Matthees ESF, Donow C, Moepps B, Premont RT, Burkhalter MD, Hoffmann C, Philipp M. J Am Soc Nephrol. 2023 Apr 1;34(4):590-606. doi: 10.1681/ASN.0000000000000082. Epub 2023 Jan 26. PMID: 36810260
  • Aging Associates with Cilium Elongation and Dysfunction in Kidney and Pancreas. 
    Adametz F, Müller A, Stilgenbauer S, Burkhalter MD, Philipp M. Adv Biol (Weinh). 2023 Aug 3:e2300194. doi: 10.1002/adbi.202300194. Online ahead of print. PMID: 37537358
  • Dutto I*, Gerhards J*, Herrera A, Souckova O, Škopová V, Smak J, Junza A, Yanes O, Boeckx C Prof, Burkhalter MD, Zikánová M, Pons S, Philipp M, Lüders J, Stracker TH. Pathway specific effects of ADSL deficiency on neurodevelopment. Elife. 2022. doi: 10.7554/eLife.70518.      * equal contribution
  • Duong Phu M, Bross S, Burkhalter MD, Philipp M (2021) Limitations and opportunities in the pharmacotherapy of ciliopathies. Pharmacology & Therapeutics. 225:10784
  • Scheffold A, Baig AH, Chen Z, von Löhneysen SE, Becker F, Morita Y, Avila AI, Groth M, Lechel A, Schmid F, Kraus JM, Kestler HA, Stilgenbauer S, Philipp M, Burkhalter MD (2020) Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells.
    Leukemia. 34(4):1125-1134.
  • Burczyk MS*, Burkhalter MD*, Casar Tena T, Grisanti L, Kauk M, Matysik S, Donow C, Kustermann M, Rothe M, Cui Y, Raad F, Laue S, Moretti A, Zimmermann WH, Wess J, Kühl M, Hoffmann C, Tilley DG, Philipp M (2019) Muscarinic receptors promote pacemaker fate at the expense of secondary conduction system tissue in zebrafish.
    JCI Insight. 4(20). pii: 121971. doi: 10.1172/jci.insight.121971.  * equal contribution
  • Halder S*, Torrecilla I*, Burkhalter MD, Popovic M, Fielden J, Vaz B, Oehler J, Lessel D, Wisemann K, Narayan Singh A, Vendrell I, Fischer R, Philipp M, Ramadan K (2019) SPRTN Protease and Checkpoint Kinase 1 Cross-Activation Loop Safeguards DNA Replication.
    Nat. Comms. 10(1):3142.    * equal contribution
  • Burkhalter MD, Sridhar A, Sampaio P, Jacinto R, Burczyk MS, Donow C, Angenendt M, Competence Network for Congenital Heart Defects Investigators, Hempel M, Walther P, Pennekamp P, Omran H, Lopes SS, Ware SM*, Philipp M* (2019) Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis.
    J Clin Invest. 129(7):2841-2855. *co-last
Have we raised your interest? Please, inquire! We are always interested in applications of highly motivated scientists.
Heart development

Molecular mechanisms underlying heart development

The heart is the first organ to develop and become functional. It is furthermore the organ that is most prone to developmental malformations which is reflected by the large number of newborns diagnosed with a congenital heart defect. We apply small chemical compound screens, mass spectrometry as well as traditional loss-of-function strategies to contribute to the current knowledge of the molecular mechanisms underlying heart development. As a model we use zebrafish embryos, which develop a simple, yet functional, compartmentalized heart within 48 hours post fertilization.

Signal transduction

Signaling networks during development

Signal transduction serves as a form of communication between and within cells. We try to explore and better understand the physiological role of signal transduction during embryonic development. How are external signals transduced into a given cell and then between different compartments within a cell? How would a change in such signaling reflect a physiological or pathological state? And how could we manipulate signaling and with that potentially develop new therapies? To address these questions we focus on G protein-coupled receptor kinases (GRKs), which control a multitude of receptor-dependent and –independent signaling pathways.

Cilia biology

Cilia in development and disease

Cilia are microtubule-based protrusions from the surface of postmitotic cells that orchestrate a plethora of cellular signaling. Motile cilia are further capable of propelling body fluids and sensing fluid flows. When cells fail to form cilia or when cilia don’t function properly diverse afflictions can develop. Such ciliopathies include congenital malformations (i.e. impaired left-right asymmetry of internal organs), infertility, retinal degeneration or polycystic kidney disease. The clinical symptoms of cilia deficiencies also resemble those of centrosome deficiencies (i.e. microcephaly). We investigate cilia formation and function using zebrafish and cells, which we manipulate or which origin from patients with cilia defects.

Genetic variants analysis

Experimental validation of patient variants

We routinely evaluate genetic variants, which have been identified in patients, for their impact on protein expression and function. As model we use yet again the zebrafish as it offers testing of patient variants in an entire organism rather than an isolated cellular system. We cooperate with human geneticists and are always happy to offer such analyses to other labs. So far, we have analyzed variants of DVC1, a gene associated with progeria, and GRK5 variants, which we detected in patients with congenital heart defects and concomitant heterotaxy.

Zertifikate und Verbände

Focus: Top Nationales Krankenhaus 2024

Die deutschen Universitätsklinika

Kooperation für Transparenz und Qualität im Gesundheitswesen

Qualitätspartnerschaft mit der PKV

Blauer Sterne Betrieb

Erfolgsfaktor Familie

Die Altersvorsorge für den Öffentlichen Dienst

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Internationale Patienten Presse