Research group "Skeletal Pathobiochemistry"

Prof. Dr. rer. nat. Sandra Pohl
Heisenberg-Professorship for Subcellular Osteology

Phone: +49 (0) 40 7410 - 55869

  • Research
  • Research
    Proteoglycan staining of chondrocytes

    The organic skeletal matrix is composed of structurally diverse macromolecules such as collagens, proteoglycans and glycoproteins. These components are synthesized and posttranslationally modified in the endoplasmic reticulum and the Golgi apparatus of chondrocytes in the cartilage and osteoblasts in the bone tissue, and finally secreted. On the other hand, degradation of skeletal matrix macromolecules is mediated by hydrolytic enzymes such as lysosomal enzymes of the matrix-resident cells. The development and maintenance of the skeleton requires constant turnover of the highly dynamic skeletal matrix in both bone and cartilage tissues.

    Pathophysiology and molecular mechanisms of children’s skeletal disorders
    Impaired metabolisms in the bone and cartilage tissue result in a number of disorders specifically in childhood including rare genetically inherited lysosomal storage diseases and osteogenesis imperfecta. Biochemically, these diseases are characterized by deficiency or inactivity of specific proteins that coordinate a plethora of molecular pathways in the bone and cartilage. In turn this results in heterogeneity of skeletal manifestations in the affected patients.

    Our research group aims to understand the molecular mechanisms balancing skeletal matrix synthesis and degradation and to elucidate the pathophysiological basis of genetically inherited skeletal disorders in childhood. Pursuing these goals, we study mouse and cell-based models of the diseases as well as patient material by the use of combined methods from biochemistry, molecular and cell biology as well as histology and immunhistochemistry in tight collaboration with various research groups both within and beyond IOBM.

  • 2022

    A homozygous hypomorphic BNIP1 variant causes an increase in autophagosomes and reduced autophagic flux and results in a spondylo-epiphyseal dysplasia.
    Holling T, Bhavani GS, von Elsner L, Shah H, Kausthubham N, Bhattacharyya SS, Shukla A, Mortier GR, Schinke T, Danyukova T, Pohl S, Kutsche K, Girisha KM (2022) Hum Mutat. doi: 10.1002/humu.24368

    Site-1 and site-2 proteases: A team of two in regulated proteolysis.
    Danyukova T, Schöneck K, Pohl S. Biochim Biophys Acta Mol Cell Res (2022) 1869: 119138


    Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III
    Di Lorenzo G, Westermann LM, Yorgan TA, Stürznickel J, Ludwig NF, Ammer LS, Baranowsky A, Ahmadi S, Pourbarkhordariesfandabadi E, Breyer SR, Board TN, Foster A, Mercer J, Tylee K, Velho RV, Schweizer M, Renné T, Braulke T, Randon DN, Sperb-Ludwig F, de Camargo Pinto LL, Moreno CA, Cavalcanti DP, Amling M, Kutsche K, Winter D, Muschol NM, Schwartz IVD, Rolvien T, Danyukova T, Schinke T, Pohl S (2021) Genet Med 23: 2369-2377

    Mucolipidosis type II and type III: a systematic review of 843 published cases
    Dogterom EJ, Wagenmakers MAEM, Wilke M, Demirdas S, Muschol NM, Pohl S, Meijden JCV, Rizopoulos D, Ploeg ATV, Oussoren E (2021) Genet Med 23: 2047-2056

    Transgenic inhibition of interleukin-6 trans-signaling does not prevent skeletal pathologies in mucolipidosis type II mice
    Westermann LM, Baranowsky A, Di Lorenzo G, Danyukova T, Soul J, Schwartz JM, Hendrickx G, Amling M, Rose-John S, Garbers C, Schinke T, Pohl S (2021) Sci Rep 11: 3556

    Is hematopoietic stem cell transplantation a therapeutic option for mucolipidosis type II?
    Ammer LS, Pohl S, Breyer SR, Aries C, Denecke J, Perez A, Petzoldt M, Schrum J, Müller I, Muschol NM (2021) Mol Genet Metab Rep 26: 100704


    Imbalanced cellular metabolism compromises cartilage homeostasis and joint function in a mouse model of mucolipidosis type III gamma
    Westermann LM, Fleischhauer L, Vogel J, Jenei-Lanzl Z, Ludwig NF, Schau L, Morellini F, Baranowsky A, Yorgan TA, Di Lorenzo G, Schweizer M, de Souza Pinheiro B, Guarany NR, Sperb-Ludwig F, Visioli F, Oliveira Silva T, Soul J, Hendrickx G, Wiegert JS, Schwartz IVD, Clausen-Schaumann H, Zaucke F, Schinke T, Pohl S*, Danyukova T* (2020) Dis Model Mech 31: 1796-1814

    Cover Image Westermann et al., Disease Models & Mechanisms Issue 31, 2020

    Distinct modes of balancing glomerular cell proteostasis in mucolipidosis type II and III prevent proteinuria
    Sachs W, Sachs M, Krüger E, Zielinsky S, Kretz O, Huber TB, Baranowsky A, Westermann LM, Velho RV, Ludwig NF, Yorgan TA, Di Lorenzo G, Kollmann K, Braulke T, Schwartz IV, Schinke T, Danyukova T, Pohl S*, Meyer-Schwesinger C* (2020) J Am Soc Nephrol 31: 1796-1814

    Hip morphology in mucolipidosis type II
    Ammer LS, Oussoren E, Muschol NM, Pohl S, Rubio-Gozalbo ME, Santer R, Stuecker R, Vettorazzi E, Breyer SR (2020) J Clin Med 9: E728

    Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes
    Hendrickx G, Danyukova T, Baranowsky A, Rolvien T, Angermann A, Schweizer M, Keller J, Schröder J, Meyer-Schwesinger C, Muschol N, Paganini C, Rossi A, Amling M, Pohl S*, Schinke T* (2020) Hum Mol Genet 29: 803-816

    Combined in-vitro and in-silico analyses of missense mutations in GNPTAB provide new insights into the molecular bases of mucolipidosis II and III alpha/beta
    Danyukova T
    , Ludwig NF, Velho RV, Harms FL, Güneş N, Tidow H, Schwartz IV, Tüysüz B, Pohl S (2020) Hum Mutat 41: 133-139


    Toward engineering the mannose 6-phosphate elaboration pathway in plants for enzyme replacement therapy of lysosomal storage disorders
    Zeng Y, He X, Danyukova T, Pohl S, Kermode AR (2019) J Clin Med 8: E2190

    Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype
    Atiskova Y, Bartsch S, Danyukova T, Becker E, Hagel C, Storch S, Bartsch U (2019) Sci Rep 9: 14185

    The lysosomal storage disorders mucolipidosis type II, type III alpha/beta and type III gamma: Update on GNPTAB and GNPTG mutations
    Velho RV
    , Harms FL, Danyukova T, Ludwig NF, Friez MJ, Cathey SS, Filocamo M, Tappino B, Güneş N, Tüysüz B, Tylee KL, Brammeier KL, Heptinstall L, Oussoren E, van der Ploeg AT, Petersen C, Alves S, Saavedra GD, Schwartz IV, Muschol N, Kutsche K, Pohl S (2019) Hum Mutat 40: 842-864

    Humoral immune response in adult Brazilian patients with mucolipidosis III gamma
    Sperb-Ludwig F, Alegra T, Velho RV, Ludwig N, Siebert M, Jobim M, Vairo F, Schwartz IVD (2019) Genet Mol Biol 42: 571-573

    A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome motility and impaired cell survival
    von Kleist L, Ariunbat K, Braren I, Stauber T, Storch S, DanyukovaT (2019) Mol Genet Metab 126: 196-205


    The lysosomal protein arylsulfatase B is a key enzyme involved in skeletal turnover
    Pohl S, Angermann A, Jeschke A, Hendrickx G, Yorgan TA, Makrypidi-Fraune G, Steigert A, Kühn SC, Rolvien T, Schweizer M, Köhne T, Neven M, Winter O, Velho RV, Albers J, Streichert T, Pestka JM, Baldauf C, Breyer S, Stuecker R, Muschol N, Cox TM, Saftig P, Paganini C, Rossi A, Amling M, Braulke T, Schinke T (2018) J Bone Miner Res 33: 2186-2201

    Cover Image Pohl et al., Journal of Bone and Mineral Research Issue 33, 2018

    Lysosomal proteome and secretome analysis identifies missorted enzymes and their non-degraded substrates in mucolipidosis III mouse cells
    Di Lorenzo G, Velho RV, Winter D, Thelen M, Ahmadi S, Schweizer M, De Pace R, Cornils K, Yorgan TA, Grüb S, Hermans-Borgmeyer I, Schinke T, Müller-Loennies S, Braulke T, Pohl S (2018) Mol Cell Proteomics 17: 1612-1626

    Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation
    Danyukova T, Ariunbat K, Thelen M, Brocke-Ahmadinejad N, Mole SE, Storch S (2018) Hum Mol Genet 27: 1711-1722


    GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase activity in mucolipidosis type II through distinct mechanisms
    Ludwig NF, Velho RV, Sperb-Ludwig F, Acosta AX, Ribeiro EM, Kim CA, Gandelman Horovitz DD, Boy R, Rodovalho-Doriqui MJ, Lourenço CM, Santos ES, Braulke T, Pohl S*, Schwartz IVD* (2017) Int J Biochem Cell Biol 92: 90-94

    Next-generation sequencing corroborates a probable de novo GNPTG variation previously detected by Sanger sequencing
    Ludwig NF, Sperb-Ludwig F, Velho RV, Schwartz IVD (2017) Mol Genet Metab Rep 11: 92-99

    Site-1 protease and lysosomal homeostasis (Review)
    Velho RV
    , De Pace R, Klünder S, Di Lorenzo G, Schweizer M, Braulke T, Pohl S (2017) Biochim Biophys Acta Mol Cell Res 1864: 2162-2168


    Identification of the interaction domains between α- and γ-subunits of GlcNAc-1-phosphotransferase
    Velho RV, De Pace R, Tidow H, Braulke T, Pohl S (2016) FEBS Lett 590: 4287-4295

    Enigmatic in vivo GlcNAc-1-phosphotransferase (GNPTG) transcript correction to wild type in two mucolipidosis III gamma siblings homozygous for nonsense mutations
    Velho RV
    , Ludwig NF, Alegra T, Sperb-Ludwig F, Guarany NR, Matte U, Schwartz IV. J Hum Genet 61: 555-560


    Analyses of disease-related GNPTAB mutations define a novel GlcNAc1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site
    Velho RV
    , De Pace R, Klünder S, Sperb-Ludwig F, Lourenço CM, Schwartz IV, Braulke T, Pohl S (2015) Hum Mol Genet 24: 3497-3505

    Site-1 protease-activated formation of lysosomal targeting motifs is independent of the lipogenic transcription control
    Klünder S
    , Heeren J, Markmann S, Santer R, Braulke T, Pohl S (2015) J Lipid Res 56: 1625-1632

    Subunit interactions of the disease-related hexameric GlcNAc-1-phosphotransferase complex
    De Pace R, Velho RV, Encarnação M, Marschner K, Braulke T, Pohl S (2015) Hum Mol Genet 24: 6826-6835

    Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation
    Pohl S
    , Hasilik A (2015) Methods Cell Biol 126: 63-83


    Mucolipidosis II-related mutations inhibit the exit from the endoplasmic reticulum and proteolytic cleavage of GlcNAc-1-phosphotransferase precursor protein (GNPTAB)
    De Pace R, Coutinho MF, Koch-Nolte F, Haag F, Prata MJ, Alves S, Braulke T, Pohl S (2014) Hum Mutat 35:368-376


    A novel mannose 6-phosphate specific antibody fragment for diagnosis of Mucolipidosis type II and III (Book chapter)
    Pohl S
    , Braulke T, Müller-Loennies S (2012) In: Anticarbohydrate antibodies - From molecular basis to clinical application (Eds: P. Kosma, S. Müller-Loennies), Springer-Verlag, Wien

    Lysosomal dysfunction causes neurodegeneration in mucolipidosis II ‘knock-in’ mice Kollmann K, Damme M, Markmann S, Morelle W, Schweizer M, Hermans-Borgmeyer I, Röchert AK, Pohl S, Lübke T, Michalski JC, Käkelä R. Walkley SU, Braulke T (2012) Brain 135: 2661-2675

    Multiple Enzyme Deficiencies: Defects in transport: Mucolipidosis II alpha/beta; mucolipidosis III alpha/beta and mucolipidosis III gamma (Book chapter)
    Raas-Rothschild A, Pohl S, Braulke T (2012) In: Lysosomal Storage Diseases: A Practical Guide (Eds. A. B. Mehta, B. Winchester), Wiley-Blackwell, Oxford


    A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism
    Marschner K, Kollmann K, Schweizer M, Braulke T, Pohl S (2011) Science 333: 87-90

    Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 disease
    Lebrun AH, Moll-Khosrawi P, Pohl S, Makrypidi G, Storch S, Kilian D, Streichert T, Otto B, Mole SE, Ullrich K, Cotman S, Kohlschütter A, Braulke T, Schulz A (2011) ) Mol Med 17: 1253-1261

    Residual activity and proteasomal degradation of p.Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndrome
    Muschol N, Pohl S, Meyer A, Gal A, Ullrich K, Braulke T (2011) Am J Med Genet A 155: 1634-1639

    Post-translational modifications of the gamma-subunit affect intracellular trafficking and complex assembly of GlcNAc-1-phosphotransferase
    Encarnação M, Kollmann K, Trusch M, Braulke T, Pohl S (2011) J Biol Chem 286: 5311-5318


    Proteolytic processing of the gamma-subunit is associated with the failure to form GlcNAc-1-phosphotransferase complexes and mannose 6-phosphate residues on lysosomal enzymes in human macrophages
    Pohl S, Tiede S, Marschner K, Encarnação M, Castrichini M, Kollmann K, Muschol N, Ullrich K, Müller-Loennie S, Braulke T (2010) J Biol Chem 285: 23936-23944

    Mannose phosphorylation in health and disease (Review)
    Kollmann K, Pohl S, Marschner K, Encarnação M, Sakwa I, Tiede S, Poorthuis BJ, Lübke T, Müller-Loennies S, Storch S, Braulke T (2010) Eur J Cell Biol 89: 117-123

    Loss of N-acetylglucosamine-1-phosphotransferase gamma-subunit due to intronic mutation in GNPTG causes mucolipidosis type III gamma: Implications for molecular and cellular diagnostics
    Pohl S, Encarnacão M, Castrichini M, Müller-Loennies S, Muschol N, Braulke T (2010) Am J Med Genet A 152: 124-132


    Compensatory expression of human N-acetylglucosaminyl-1 phosphotransferase subunits in mucolipidosis type III gamma
    Pohl S
    , Tiede S, Castrichini M, Cantz M, Gieselmann V, Braulke T (2009) Biochim Biophys Acta 1792: 221-225

    Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases (Review)
    Pohl S, Marschner K, Storch S, Braulke T (2009) Biol Chem 390:521-7

    Identification and molecular characterization of six novel mutations in the UDP-N-acetylglucosamine-1-phosphotransferase gamma subunit (GNPTG) gene in patients with mucolipidosis III gamma
    Persichetti E, Chuzhanova NA, Dardis A, Tappino B, Pohl S, Thomas NS, Rosano C, Balducci C, Paciotti S, Dominissini S, Montalvo AL, Sibilio M, Parini R, Rigoldi M, Di Rocco M, Parenti G, Orlacchio A, Bembi B, Cooper DN, Filocamo M, Beccari T (2009) Hum Mutat 30: 978-984


    Molecular analysis of the GlcNac-1-phosphotransferase (Review)
    Braulke T, Pohl S, Storch S (2008) J Inherit Metab Dis 31: 253-257


    C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes
    Storch S, Pohl S, Quitsch A, Falley K, Braulke T (2007) Traffic 8: 431-44

    Increased expression of lysosomal acid phosphatase (LAP/Acp2) in CLN3-defective cells and mouse brain tissue
    Pohl S, Mitchison HM, Kohlschütter A, van Diggelen, O, Braulke T, Storch S (2007) J Neurochem 103: 2177-2188


    A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the Batten disease-related CLN3 Protein are required for efficient lysosomal targeting
    Storch S, Pohl S, Braulke T (2004) J Biol Chem 279: 53625-53634

  • Current Funding

    2023 - 2026
    German Research Foundation (DFG)
    Research Grant „The molecular role of site-2 protease for osteblast function“

    2023 - 2025
    Werner Otto Stiftung
    Research Grant „Distinct roles of site-1 and site-2 proteases in the pathogenesis of rare inherited connective tissue diseases of childhood“

    2022 - 2026
    German Research Foundation (DFG)
    Heisenberg Grant „Pathophysiology and molecular bases of skeletal disorders in childhood“

    2018 - 2025
    German Research Foundation (DFG)
    Research Grant „Role of the gamma-subunit of the GlcNAc-1-phosphotransferase complex for selective mannose 6-phosphate modifications on lysosomal enzymes“

    Former Funding

    2010 - 2022
    German Research Foundation (DFG)
    Collaborative Research Centre 877:
    "Proteolysis as a Regulatory Event in Pathophysiology"

    2017 - 2018
    ISMRD - International Society for Mannosidosis & Related Diseases (USA)
    "Osteoporosis in Mucolipidosis II - A potential corrective approach"

    2012 - 2017
    German Research Foundation (DFG)
    Research Training Group 1459:
    "Sorting and Interactions between Proteins of Subcellular Compartments"

  • Bachelor’s and Master’s students are an integral part of our research team. We offer Bachelor’s and Master’s thesis research projects that focus on the pathomechanisms of skeletal diseases.

    We always welcome excellent MD and PhD students and postdoctoral researchers who are interested in our research and are willing to apply for scholarships to join our lab.

    We also invite medical students of UKE to do their student studies (‘Studienarbeit’) on a topic related to bone and/or cartilage pathologies as well as molecular pathomechanisms of these diseases and current therapeutic strategies to combat them.

    Please send your requests to Prof. Dr. Sandra Pohl ( or Dr. Tatyana Danyukova (