Ingo Nolte

University of Veterinary Medicine Hannover, Hanover, Lower Saxony, Germany

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Publications (319)453.54 Total impact

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    ABSTRACT: Alterations in muscle recruitment are key to the functional plasticity of the mammalian locomotor system. One particularly challenging situation quadrupeds may face is when the functionality of a limb is reduced or lost. To better understand how mammals manage in such situations and which muscular adaptations they exhibit when locomoting on three legs, we recorded the activity patterns of two limb and one back extensor muscle in nine dogs using surface electromyography. We compared the timing and the level of recruitment before and after the loss of a hindlimb was simulated. Both the intensity and the timing of the activity changed significantly in the m. vastus lateralis of the remaining hindlimb, consistent with this limb bearing a greater proportion of the body weight as well as with previously reported kinematic changes. In accordance with the greater body weight supported by the forelimbs, the m. triceps brachii showed first and foremost an increased level of excitation. The very asymmetrical changes in the timing and the level of activity in the m. longissimus dorsi reflects the highly asymmetrical functional requirements imposed on the trunk and the pelvis when one hindlimb is no longer involved in the production of locomotor work while the other hindlimb partially compensates the loss. Integration of our electromyographical findings with kinetic and kinematic results illustrates that dogs exhibited a well-coordinated response to the functional requirements of tripedalism and underlines the importance of moment-to-moment modulation in muscular recruitment for the functional plasticity of the mammalian locomotor system. J. Exp. Zool. 9999A: XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Experimental Zoology Part A Ecological Genetics and Physiology 07/2015; DOI:10.1002/jez.1936 · 1.35 Impact Factor
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    ABSTRACT: A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.
    PLoS ONE 07/2015; 10(7):e0131280. DOI:10.1371/journal.pone.0131280 · 3.23 Impact Factor
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    ABSTRACT: Degradable implant material for bone remodeling that corresponds to the physiological stability of bone has still not been developed. Promising degradable materials with good mechanical properties are magnesium and magnesium alloys. However, excessive gas production due to corrosion can lower the biocompatibility. In the present study we used the polymer coating polycaprolactone (PCL), intended to lower the corrosion rate of magnesium. Additionally, improvement of implant geometry can increase bone remodeling. Porous structures are known to support vessel ingrowth and thus increase osseointegration. With the selective laser melting (SLM) process, defined open porous structures can be created. Recently, highly reactive magnesium has also been processed by SLM. We performed studies with a flat magnesium layer and with porous magnesium implants coated with polymers. The SLM produced magnesium was compared with the titanium alloy TiAl6V4, as titanium is already established for the SLM-process. For testing the biocompatibility, we used primary murine osteoblasts. Results showed a reduced corrosion rate and good biocompatibility of the SLM produced magnesium with PCL coating.
    International Journal of Molecular Sciences 06/2015; 16(6):13287-13301. DOI:10.3390/ijms160613287 · 2.86 Impact Factor
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    ABSTRACT: Displacement of canine intervertebral disk material can be seen directly in diagnostic imaging modalities such as magnetic resonance imaging and computed tomographic imaging. Canine intervertebral disk herniation can be differentiated into Hansen type 1 and 2 categories by clinical appearance, but anular- and nuclear disk material cannot be distinguished in computed tomographic images. Therefore, we hypothesized that the "Disk extension beyond the interspace"-nomenclature that describes the displacement by the disk contour might aid diagnosis. The aim of this study was to test the reliability of the "Disk extension beyond the interspace"-nomenclature in the evaluation of canine intervertebral disks via magnetic resonance and computed tomographic imaging. Magnetic resonance and computed tomographic images of 144 intervertebral disks of 43 dogs were evaluated by 3 observers with different degrees of experience from 2 institutions retrospectively. A substantial intraobserver agreement was found, while interobserver agreement was fair to moderate with significant differences in evaluation. Comparison of imaging methods showed a fair to moderate agreement without statistically significant differences in evaluation. DEBIT-nomenclature cannot be recommended for veterinary clinical usage yet. The largest variability was found in the evaluation of the bulged canine intervertebral disk. The observers' experience and the imaging method influenced DEBIT- evaluation only slightly, while training and working at different institutions influenced DEBIT-evaluation strongly.
    BMC Veterinary Research 05/2015; 11(1):110. DOI:10.1186/s12917-015-0421-x · 1.74 Impact Factor
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    ABSTRACT: Canine lymphoma has lately drawn focus as a model of human non-Hodgkin's lymphoma due to its spontaneous occurrence and similar biological behavior. Cells with stem cell-like characteristics are believed to play a key role in therapeutic failure. Thus, an initial characterization and the possibility of specific detection of such cells could bear significant value. Expression of 12 stem cell markers were analyzed in two canine B-cell lymphoma cell lines, their generated spheres, and in primary lymphoma samples by quantitative real-time polymerase chain reaction and partially by flow cytometry and immunocytochemistry. Expression of maternal embryonic leucine zipper kinase (Melk) was significantly higher in CLBL-1, CLBL-1M and in primary B-cell lymphoma samples compared to non-neoplastic lymph nodes. Spheres displayed a higher expression of v-myc myelocytomatosis viral oncogene homolog (Myc) and lower expression of Cd44 compared to original cell lines and primary B-cell lymphoma samples. The results suggest a potential interesting role of Melk in canine B-cell lymphoma. Furthermore, the up-regulation of Myc in serum-free-generated spheres offers interesting possibilities for functional assays characterizing the specific generated sub-population. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 05/2015; 35(5):2805-16. · 1.87 Impact Factor
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    ABSTRACT: BACKGROUND: Canine prostate cancer represents a spontaneous animal model for the human counterpart. Cells with stem cell-like character are considered to play a major role in therapeutic resistance and tumor relapse. Thus, the identification of markers allowing for recognition and characterization of these cells is essential. MATERIALS AND METHODS: Expression of 12 stem cell marker genes in the canine prostate cancer cell line CT1258 and spheroid cells generated from these was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as proliferation and doxorubicin resistance. RESULTS: Integrin alpha-6 (ITGA6) expression and metabolic activity were significantly up-regulated in CT1258-derived spheroid cells, while doxorubicin resistance remained comparable. CONCLUSION: ITGA6 de-regulation and metabolic activity appear to be characteristic of the generated spheres, indicating potential intervention targets.
    Anticancer research 04/2015; 35(4):1917-27. · 1.87 Impact Factor
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    ABSTRACT: BACKGROUND:Canine prostate cancer represents a spontaneous animal model for the human counterpart. Cells with stem cell-like character are considered to play a major role in therapeutic resistance and tumor relapse. Thus, the identification of markers allowing for recognition and characterization of these cells is essential. MATERIALS AND METHODS: Expression of 12 stem cell marker genes in the canine prostate cancer cell line CT1258 and spheroid cells generated from these was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as proliferation and doxorubicin resistance. RESULTS: Integrin alpha-6 (ITGA6) expression and metabolic activity were significantly up-regulated in CT1258-derived spheroid cells, while doxorubicin resistance remained comparable. CONCLUSION: ITGA6 de-regulation and metabolic activity appear to be characteristic of the generated spheres, indicating potential intervention targets. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. KEYWORDS: Prostate cancer; cancer stem cell marker; canine cancer stem cells; spheroid cell clusters
    Anticancer research 04/2015; 35(4):1917-1927. · 1.87 Impact Factor
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    ABSTRACT: To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. OPEN ACCESS Int. J. Mol. Sci. 2015, 16 7479 The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.
    International Journal of Molecular Sciences 04/2015; 16(4):7478-7492. DOI:10.3390/ijms16047478 · 2.86 Impact Factor
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    ABSTRACT: Canine prostate cancer represents a spontaneous animal model for the human counterpart. Cells with stem cell-like character are considered to play a major role in therapeutic resistance and tumor relapse. Thus, the identification of markers allowing for recognition and characterization of these cells is essential. Expression of 12 stem cell marker genes in the canine prostate cancer cell line CT1258 and spheroid cells generated from these was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as proliferation and doxorubicin resistance. Integrin alpha-6 (ITGA6) expression and metabolic activity were significantly up-regulated in CT1258-derived spheroid cells, while doxorubicin resistance remained comparable. ITGA6 de-regulation and metabolic activity appear to be characteristic of the generated spheres, indicating potential intervention targets. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 04/2015; 35(4):1917-27. · 1.87 Impact Factor
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    B. Goldner · A. Fuchs · I. Nolte · N. Schilling
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    ABSTRACT: Limb amputation often represents the only treatment option for canine patients with certain diseases or injuries of the appendicular system. Previous studies have investigated adaptations to tripedal locomotion in dogs but there is a lack of understanding of biomechanical compensatory mechanisms. This study evaluated the kinematic differences between quadrupedal and tripedal locomotion in nine healthy dogs running on a treadmill. The loss of the right pelvic limb was simulated using an Ehmer sling. Kinematic gait analysis included spatio-temporal comparisons of limb, joint and segment angles of the remaining pelvic and both thoracic limbs. The following key parameters were compared between quadrupedal and tripedal conditions: angles at touch-down and lift-off, minimum and maximum joint angles, plus range of motion. Significant differences in angular excursion were identified in several joints of each limb during both stance and swing phases. The most pronounced differences concerned the remaining pelvic limb, followed by the contralateral thoracic limb and, to a lesser degree, the ipsilateral thoracic limb. The thoracic limbs were, in general, more retracted, consistent with pelvic limb unloading and previous observations of bodyweight re-distribution in amputees. Proximal limb segments showed more distinct changes than distal ones. Particularly, the persistently greater anteversion of the pelvis probably affects the axial system. Overall, tripedal locomotion requires concerted kinematic adjustments of both the appendicular and axial systems, and consequently preventive, therapeutic and rehabilitative care of canine amputees should involve the whole musculoskeletal apparatus. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Veterinary Journal 03/2015; 204(2). DOI:10.1016/j.tvjl.2015.03.003 · 2.17 Impact Factor
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    International Journal of Oral and Maxillofacial Surgery 03/2015; 44(5). DOI:10.1016/j.ijom.2015.02.012 · 1.36 Impact Factor
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    ABSTRACT: Doxorubicin has been shown to be cardiotoxic at high doses but is an efficacious chemotherapeutic agent in the treatment of canine lymphoma. Echocardiographic measurements and serum ultrasensitive cardiac troponin I (cTnI) levels were obtained before and after doxorubicin administration in 14 dogs diagnosed with lymphoma. The aim of this prospective study was to evaluate changes in cTnI concentrations and tissue velocity imaging (TVI) values in dogs with lymphoma undergoing chemotherapy with doxorubicin. A total of 182 cTnI and 1017 TVI measurements were performed. Standard echocardiographic parameters, tissue Doppler indices and cTnI concentrations did not differ at any time point within a 12-week cyclic combination protocol. In conclusion, the use of doxorubicin at standard doses in the treatment of canine lymphoma may not be associated with significant myocardial damage. © 2015 John Wiley & Sons Ltd.
    Veterinary and Comparative Oncology 02/2015; DOI:10.1111/vco.12135 · 1.45 Impact Factor
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    ABSTRACT: Background In molecular medicine, the manipulation of cells is prerequisite to evaluate genes as therapeutic targets or to transfect cells to develop cell therapeutic strategies. To achieve these purposes it is essential that given transfection techniques are capable of handling high cell numbers in reasonable time spans. To fulfill this demand, an alternative nanoparticle mediated laser transfection method is presented herein. The fs-laser excitation of cell-adhered gold nanoparticles evokes localized membrane permeabilization and enables an inflow of extracellular molecules into cells.ResultsThe parameters for an efficient and gentle cell manipulation are evaluated in detail. Efficiencies of 90% with a cell viability of 93% were achieved for siRNA transfection. The proof for a molecular medical approach is demonstrated by highly efficient knock down of the oncogene HMGA2 in a rapidly proliferating prostate carcinoma in vitro model using siRNA. Additionally, investigations concerning the initial perforation mechanism are conducted. Next to theoretical simulations, the laser induced effects are experimentally investigated by spectrometric and microscopic analysis. The results indicate that near field effects are the initial mechanism of membrane permeabilization.Conclusion This methodical approach combined with an automated setup, allows a high throughput targeting of several 100,000 cells within seconds, providing an excellent tool for in vitro applications in molecular medicine. NIR fs lasers are characterized by specific advantages when compared to lasers employing longer (ps/ns) pulses in the visible regime. The NIR fs pulses generate low thermal impact while allowing high penetration depths into tissue. Therefore fs laser could be used for prospective in vivo applications.
    Journal of Nanobiotechnology 02/2015; 13(1):10. DOI:10.1186/s12951-014-0057-1 · 4.08 Impact Factor
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    ABSTRACT: Canine prostate cancer (PC) is a highly aggressive malignancy. However, in contrast to man, neither standard screening strategies nor curative therapeutic options exist for the companion animal. A prostate-specific membrane antigen (PSMA) screening as molecular marker akin to human PC is currently not available for dogs as data on specific canine PSMA detection are contradictory. To evaluate an antibody for specific canine PSMA detection by western blotting (WB), lysates of three canine prostatic cell lines (CT1258, DT08/40, DT08/46) were comparatively analyzed by WB and mass spectrometry (MS) to the human cell lines VCaP, LnCaP and PC-3. MS analyses of the detected canine proteins confirmed cross reactivity of the antibody clone YPSMA-1 with canine PSMA. The MS analyses of the extracted canine protein bands proved that the YPSMA-1 clone is as well specific for canine PSMA in WB and, thus, represents a reliable tool for comparative PSMA studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 01/2015; 35(1):145-8. · 1.87 Impact Factor
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    ABSTRACT: Stage migration is described in humans and dogs as a sequel of using more sensitive diagnostic methods. One hundred eighty-six dogs with multicentric lymphoma were enrolled with results of conventional staging as well as ultrasonographic and cytological examination of liver and spleen being available. The addition of splenic respective hepatic ultrasound and cytology findings resulted in slightly lower number of dogs classified as having liver and spleen involvement. In dogs with multicentric lymphoma, addition of cytology led to a significant shift of individuals from stage IV to stage III. Findings of hepatic and splenic ultrasound and cytology exerted no significant influence on complete remission and survival durations in dogs with combination chemotherapy. Staging methodology in canine lymphoma should be redefined, considering that the prognostic significance of splenic and hepatic ultrasound and cytology warrants further investigation. © 2014 John Wiley & Sons Ltd.
    Veterinary and Comparative Oncology 12/2014; DOI:10.1111/vco.12127 · 1.45 Impact Factor
  • 2nd International Conference on Predictive, Preventive and Personalized Medicine and Molecular Diagnostics, Las Vegas, NV, USA; 11/2014
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    ABSTRACT: Gold nanoparticle mediated (GNOME) laser transfection is a powerful technique to deliver small biologically relevant molecules into cells. However, the transfection of larger and especially negatively charged DNA remains challenging. The efficiency for pDNA was 0.57% using parameter that does not influence the endo- and exogenous DNA. In order to gain a deeper understanding of the actual molecule uptake process, the uptake efficiency was determined using molecules of different sizes. It was evaluated that uncharged dextran molecules (2000 kDa) were delivered with an efficiency of 68%. The intracellular distribution of injected molecules was visualized and larger molecules were primary found in the cytoplasm. Patch clamp measurements suggested a permeabilization time up to 15 minutes. The uptake efficiency depended on the size and charge of the molecule to deliver as well as the cell size. A minor role for transfection plays the cell type since primary stem cells were successfully transfected. The perforation efficiency of semi-adherent and suspension cells is influenced by the cell and molecule size.
    Journal of Biophotonics 11/2014; 9999(9999). DOI:10.1002/jbio.201400065 · 3.86 Impact Factor
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    ABSTRACT: Background Right ventricular (RV) volume and function are important diagnostic and prognostic factors in dogs with primary or secondary right-sided heart failure. The complex shape of the right ventricle and its retrosternal position make the quantification of its volume difficult. For that reason, only few studies exist, which deal with the determination of RV volume parameters. In human medicine cardiac magnetic resonance imaging (CMRI) is considered to be the reference technique for RV volumetric measurement (Nat Rev Cardiol 7(10):551-563, 2010), but cardiac computed tomography (CCT) and three-dimensional echocardiography (3DE) are other non-invasive methods feasible for RV volume quantification. The purpose of this study was the comparison of 3DE and CCT with CMRI, the gold standard for RV volumetric quantification.Results3DE showed significant lower and CCT significant higher right ventricular volumes than CMRI. Both techniques showed very good correlations (R¿>¿0.8) with CMRI for the volumetric parameters end-diastolic volume (EDV) and end-systolic volume (ESV). Ejection fraction (EF) and stroke volume (SV) were not different when considering CCT and CMRI, whereas 3DE showed a significant higher EF and lower SV than CMRI. The 3DE values showed excellent intra-observer variability (<3%) and still acceptable inter-observer variability (<13%).ConclusionCCT provides an accurate image quality of the right ventricle with comparable results to the reference method CMRI. CCT overestimates the RV volumes; therefore, it is not an interchangeable method, having the disadvantage as well of needing general anaesthesia. 3DE underestimated the RV-Volumes, which could be explained by the worse image resolution. The excellent correlation between the methods indicates a close relationship between 3DE and CMRI although not directly comparable. 3DE is a promising technique for RV volumetric quantification, but further studies in awake dogs and dogs with heart disease are necessary to evaluate its usefulness in veterinary cardiology.
    BMC Veterinary Research 10/2014; 10(1):242. DOI:10.1186/s12917-014-0242-3 · 1.74 Impact Factor
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    ABSTRACT: Objective: Although the classification of canine intervertebral disc degeneration using magnetic resonance imaging (MRI) has been described in the literature, there is no such classification using computed tomographic imaging. Because computed tomography (CT) is a frequently used diagnostic imaging tool in veterinary medicine, the aim of this study was the introduction and validation of such a scoring system. T2-weighted magnetic resonance images were available for comparative analysis. Material and methods: A total of 43 dogs were examined using CT and MRI. Image data records of 144 intervertebral discs were blinded, randomized and evaluated twice by three observers. CT data were analyzed using a self-developed scoring system, while MRI data sets were evaluated using the Pfirrmann scoring system. Intra- and interobserver agreement were determined using Statistical Analysis Software (SAS). Results: Intra- and interobserver agreement were mostly substantial in the Pfirrmann (0.58-0.77) and self-developed (0.60-0.81) scoring systems. A slight agreement was found between both classification systems (κ scores 0.26-0.29). Conclusion and clinical relevance: The self-developed scoring system allows a reliable assessment of canine intervertebral disc degeneration using CT imaging. Therefore, further diagnostic and prognostic information can be obtained. Degenerative changes in the intervertebral discs could be identified at an earlier stage when using MRI in comparison with CT.
    Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere 10/2014; 42(6). DOI:10.15654/TPK-140228 · 0.47 Impact Factor

Publication Stats

2k Citations
453.54 Total Impact Points

Institutions

  • 1998–2015
    • University of Veterinary Medicine Hannover
      • • Klinik für Kleintiere
      • • Institute of Animal Breeding and Genetics
      • • Institute of Animal Ecology and Cell Biology
      Hanover, Lower Saxony, Germany
  • 2012
    • Ludwig-Maximilians-University of Munich
      • Faculty of Veterinary Medicine
      München, Bavaria, Germany
  • 2009
    • Leibniz Universität Hannover
      • Institute of Metal Forming and Metal Forming Machines
      Hannover, Lower Saxony, Germany
  • 1999–2008
    • Universität Bremen
      • Center for Human Genetics and Genetic Counselling (ZHG)
      Bremen, Bremen, Germany
  • 1997–2004
    • Hannover Medical School
      • Laboratory Animal Science
      Hanover, Lower Saxony, Germany