Josephine T. Tauer

Josephine T. Tauer
McGill University | McGill · Faculty of Dentistry; Shriners Hospital

PhD

About

107
Publications
7,124
Reads
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608
Citations
Additional affiliations
November 2017 - present
McGill University
Position
  • PostDoc Position
November 2015 - October 2017
McGill University
Position
  • PostDoc Position
July 2013 - October 2015
Universitätsklinikum Carl Gustav Carus Dresden
Position
  • Laboratory Manager
Education
March 2009 - July 2013
Technical University Dresden, Faculty of Medicine Carl Gustav Carus
Field of study
  • Univeristy Hospital Carl Gustav Carus, Department of Pediatrics
March 2006 - July 2008
Brandenburg University of Technology Cottbus - Senftenberg
Field of study
  • Biotechnology - Specialism Applied Microbiology
September 2002 - February 2006

Publications

Publications (107)
Article
Full-text available
Pediatric patients with Osteogenesis Imperfecta (OI), a heritable connective tissue disorder, frequently suffer from long bone deformations. Surgical correction often results in bone non-unions, necessitating revision surgery with autogenous bone grafting using bone-marrow-derived stem cells (BM-SC) to regenerate bone. BM-SC harvest is generally in...
Article
Full-text available
Male and female mice with a dominant severe bone fragility disorder, osteogenesis imperfecta, and their wild-type littermates (FVB background) were challenged with a long-term (26 weeks) high-fat diet to evaluate the development of obesity and glucose intolerance. Here we present data for the measurements of body mass, the outcome of glucose tolera...
Article
Full-text available
Objective: The objective of the current study is to assess the effect of a seven-week voluntary wheel running intervention on muscles and bones properties in a mouse model mimicking dominant severe osteogenesis imperfecta (OI). Methods: Female wild-type (WT) and OI (Col1a1Jrt/+) mice either performed voluntarily wheel-running exercise for 7-week...
Article
Previously we have shown that young mice with a dominant severe form of osteogenesis imperfecta (OI), caused by mutated collagen type I, exhibit an altered glucose/insulin metabolism and energy expenditure along with elevated levels of osteocalcin, a bone-derived hormone involved in the regulation of whole-body metabolism. This study aimed to exami...
Article
Full-text available
Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss‐of‐function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b‐B, re...
Article
Osteogenesis imperfecta (OI) caused by mutations affecting the extracellular matrix protein collagen type I is characterized by fragile bones and low muscle mass and function. Activin A and myostatin, members of the TGF-β superfamily, play a key role in the control of muscle mass and in muscle-bone communication. Here we investigated activin A/myos...
Article
Full-text available
Tyrosine kinase inhibitors (TKIs), such as imatinib (IMA) and nilotinib (NIL), are the cornerstone of chronic myeloid leukemia (CML) treatment via the blockade of the oncogenic BCR-ABL1 fusion protein. However, skeletal side effects are commonly observed in pediatric patients receiving long-term treatment with IMA. Additionally, in vitro studies ha...
Article
Full-text available
Osteogenesis imperfecta (OI) is a monogenetic bone fragility disorder that usually is caused by mutations in one of the two genes coding for collagen type I alpha chains, COL1A1 or COL1A2. Mutations in at least 18 other genes can also lead to an OI phenotype. As genetic testing is more widely used, mutations in these genes are also more frequently...
Article
Full-text available
Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap-/- mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF-β) neutralizing antibody 1D11 rescues the bon...
Conference Paper
Objective: Osteogenesis imperfecta (OI) is a genetic disorder mainly caused by mutations in collagen type I, and characterised by high bone turnover leading to low bone mass and high fracture rates. Recently, we have shown that young Col1a1Jrt/+ mice - mouse model of severe OI - exhibit beside high bone turnover, altered glucose/insulin metabolism,...
Article
Full-text available
A total of 156 patients (age range 1.3-18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib up-front (300, 400, 500 mg/m2, respectively) within a prospective phase III trial. Therapy response, progression-free survi...
Chapter
Full-text available
The tyrosine kinase (TK) inhibitor (TKI) imatinib provides a highly effective treatment for chronic myeloid leukemia (CML) targeting at the causative oncogenic TK BCR-ABL1. However, imatinib exerts off-target effects by inhibiting other TKs that are involved e.g. in bone metabolism. Clinically, CML patients on imatinib exhibit altered bone metaboli...
Article
Full-text available
BACKGROUND: Osteogenesis imperfecta (OI) is most often caused by mutations in type I collagen genes. Respiratory complications have been largely attributed to spine and ribcage deformities. We hypothesized that direct involvement of the pulmonary parenchyma and/or diaphragm by the disease may occur. METHODS: In Col1a1Jrt/+ mice, a model of severe...
Article
Purpose Results of the prospective trial "CML-PAED-II" assessing treatment efficacy and side effects in children and adolescents with newly diagnosed chronic myeloid leukemia (CML) are reported. Patients and Methods 156 patients (age range 1.3-18.0 years, 91 male) with newly diagnosed CML (N= 146 chronic phase (CML-CP), N= 3 accelerated phase (CML-...
Article
Full-text available
Prolonged treatment with tyrosine kinase inhibitors (TKI) including imatinib (IMA) or nilotinib (NIL), induces severe disturbances of bone metabolism in patients with chronic myeloid leukaemia. As vitamin D3 (VD3) is involved in the complex cycle of bone remodelling, the present study investigated in vitro, the influence of IMA and NIL on VD3 metab...
Conference Paper
Full-text available
Objective: Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but also by reduced muscle mass and function. Muscle mass and bone mass are closely linked, wherefore an intervention that increases muscle mass should also increase bone mass. Here we investigated the effect of a novel GDF ligand trap (Acceleron Pharma) on skeletal m...
Article
Full-text available
Osteogenesis Imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2. Osteocalcin is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rate...
Conference Paper
Full-text available
Objective Osteogenesis imperfecta (OI) is primarily characterized by bone fragility but is also associated with lower muscle mass and function. As muscle mass and bone mass are closely linked, an intervention that increases muscle mass should also increase bone mass. Here we investigated the effect of a novel activin receptor IIB ligand trap, ACE-2...
Conference Paper
Full-text available
Background: Pediatric patients with chronic myeloid leukemia (CML) are exposed to off-target side effects from long-term treatment with tyrosine kinase inhibitors (TKIs) which have been observed with increasing watchfulness in the last years (Hijiya N, et al. BLOOD 127:392, 2016). TKIs inhibit c-kit and platelet-derived growth factor receptors (PDG...
Article
Background: Pediatric patients with chronic myeloid leukemia (CML) are exposed to off-target side effects from long-term treatment with tyrosine kinase inhibitors (TKIs) which have been observed with increasing watchfulness in the last years (Hijiya N, et al. BLOOD 127:392, 2016). TKIs inhibit c-kit and platelet-derived growth factor receptors (PDG...
Article
Full-text available
Tyrosine kinase inhibitors (TKI) provide an efficient ‘targeted’ therapy against the constitutively expressed BCR-ABL1 oncoprotein characterizing chronic myeloid leukemia (CML). Due to its success in adult CML patients, the continuing treatment with TKI, namely imatinib, has also replaced
Conference Paper
Full-text available
Osteogenesis imperfecta (OI) is a heritable bone disorder characterised by bones fragility and fractures, mainly caused by dominant mutation of the collagen genes (COL1A1/COL1A2). Beside bone fragility young OI patients also exhibit lower muscle mass and strength in their lower limb compared to controls (Veilleux LN et al. Bone 2015, 79; Veilleux L...
Conference Paper
Full-text available
Osteogenesis imperfecta (OI) is caused by either mutations of type I collagen (dominant OI) or of its post-translational modification machinery (recessive OI); leading to characteristic brittle bones, fractures and extraskeletal manifestations. In mouse models of recessive (Crtap-/-) and dominant OI (Col1a2tm1.1Mcbr) bone phenotype could be correct...
Conference Paper
Introduction: L’ostéogenèse imparfaite (OI) est une maladie osseuse caractérisée par de multiples fractures. L’OI est généralement causée par une mutation dominante des gènes du collagène (COL1A1/COL1A2). Nos récentes études ont démontré que les jeunes patients atteints ont une force et une puissance musculaire plus faible au niveau du membre infér...
Conference Paper
Full-text available
Background: Childhood and adolescence is characterized by significant physiological alterations including host factors relevant for CML disease course and therapy, e.g. maturation of the immune system and skeletal growth. When compared to adults, minors with CML present with higher disease burden at diagnosis, in particular more frequently in advan...
Article
Background: Childhood and adolescence is characterized by significant physiological alterations including host factors relevant for CML disease course and therapy, e.g. maturation of the immune system and skeletal growth. When compared to adults, minors with CML present with higher disease burden at diagnosis, in particular more frequently in advan...
Article
Objectives: Tyrosine kinase inhibitors (TKIs) demonstrate outstanding efficacy for treatment of CML, however, also exert well-known off-target effects. Among these, inhibition of osteoclast's and osteoblast's growth and differentiation [Vandyke K et al Blood 2010] results in longitudinal growth impairment in children and adolescents [Shima H et al...
Conference Paper
Full-text available
Objectives: Tyrosine kinase inhibitors (TKIs) demonstrate outstanding efficacy for treatment of CML, however, also exert well-known off-target effects. Among these, inhibition of osteoclast's and osteoblast's growth and differentiation [Vandyke K et al Blood 2010] results in longitudinal growth impairment in children and adolescents [Shima H et al...
Conference Paper
Full-text available
Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. A...
Article
Full-text available
The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediat...
Conference Paper
Objectives: The tyrosine kinase inhibitor (TKI) IMA has been licensed for treatment of CML in pediatric patients in the year 2003. IMA inhibits the oncogenic BCR-ABL tyrosine kinase causing CML, but is also well known for its inhibitory “off-target” effects on bone metabolism resulting in disturbed bone remodeling. This leads to longitudinal growth...
Conference Paper
Background: In pediatric patients suffering from chronic myeloid leukemia (CML) long-term tyrosine kinase inhibitor (TKI) treatment exposes several off-target side effects. TKIs inhibit c-kit and platelet derived growth factor receptor (PDGFR) which in testes are essentially required for spermatogenesis. The influence of TKI long-term treatment on...
Conference Paper
Background: Long-term tyrosine kinase inhibitor (TKI) “targeted” treatment in pediatric patients with chronic myeloic leukemia reveals multiple off-target side effects. Specifically in testes, TKIs signaling cascades necessary for spermatogenesis are inhibited but the detailed action is not yet fully understood. Therefore, we investigated testicula...
Conference Paper
Background: Application of DA in adults with CML may lead to adverse cardiac effects (pleural & pericardial effusion, abnormal heart rate, organ hypertrophy). Understanding underlying mechanisms is crucial for the application of DA in pediatrics. Methods: DA was administered chronically [either standard (SD) or high dose (HD)) or intermittently HD...
Conference Paper
Objective: To investigate alteration of body height, BMI, and bone metabolism in a pediatric CML cohort on upfront IM treatment. Methods: During therapy standard deviation scores (SDS) of body height, body weight, urine and serum were collected in 3-month (mo) intervals. Results: 27 / 111 prepubertal pts (age: < 10 y; 14 ♂ / 13 ♀), 46 pts puberta...
Article
Full-text available
In contrast to adult medicine, specific scoring systems predicting the treatment response for an individual pediatric patient (pt) with chronic myeloid leukemia (CML) have not yet been defined. We evaluated to what extend prognostic scores as described for adults (e.g., Sokal, Hasford, EUTOS score) resulted in comparable risk group categorizations...
Article
Full-text available
The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediat...
Article
Full-text available
Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of the BCR‑ABL1 fusion gene, a constitutively active, oncogenic tyrosine kinase that is responsible for the clinical features of CML. Tyrosine kinase inhibitors, such as imatinib, have markedly altered the treatment of CML. However, tyrosine kinase inhibito...
Conference Paper
Full-text available
Objectives: A decade after being licensed for treatment of CML in minors, the TKI imatinib (IMA) is well known for it’s inhibitory “off-target” effects on activity and proliferative capacity of osteoclasts and osteoblasts resulting in impaired bone remodeling (Vandyke K et al 2010 Blood 115:766; Tauer JT et al Blood 2011:118). This causes longitudi...
Article
Background: CML is rare in pediatrics; <20 patients (pts) younger than 18 yrs are diagnosed in Germany annually. So far only imatinib (IMA) is fully licensed for treatment of pediatric CML while off-label use of 2nd generation tyrosine kinase inhibitors (TKIs) dasatinib (DASA) or nilotinib (NILO) is possible and is reimbursed by most German insuran...
Article
Objectives: A decade after being licensed for treatment of CML in minors, the TKI imatinib (IMA) is well known for it's inhibitory “off-target” effects on activity and proliferative capacity of osteoclasts and osteoblasts resulting in impaired bone remodeling (Vandyke K et al 2010 Blood 115:766; Tauer JT et al Blood 2011:118). This causes longitudi...
Article
Approximately 40% of adults with chronic myeloid leukemia (CML) in prolonged complete molecular response (CMR) remain in CMR after imatinib discontinuation. Corresponding information in children is lacking. Two children with CML in CMR for 48 and 19 months after imatinib discontinuation showed low-level fluctuating disease at RNA transcript and gen...
Article
Full-text available
Background: The impact of exposure to the tyrosine kinase inhibitor (TKI) imatinib (IMA) on the male reproductive endocrine system is still discussed controversially. We therefore investigated testosterone (Testo) and inhibin B (InB) in blood serum from male adolescents with chronic myeloid leukemia (CML) under long-term TKI treatment. Also long-te...
Conference Paper
Full-text available
Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a hybrid gene and its up-regulated activity of the tyrosine kinase (TK) BCR-ABL1. TK inhibitors like imatinib (IMA) inhibit this TK and have therefore changed the therapy of CML dramatically. However, IMA exerts side effects on bone metabolism in adult and pediatric pat...
Article
Early recognition of children with chronic phase chronic myeloid leukaemia (CML-CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because therapy options in CML-LyBC are limited. We used Multiplex Ligation-dependent Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy number alterations (CNAs) (e.g....
Conference Paper
Background Tyrosine kinase inhibitors (TKIs) such as imatinib (IMA), dasatinib (DASA), and bosutinib (BOSU) inhibit the oncogenic BCR-ABL tyrosine kinase in patients with chronic myeloid leukemia (CML). In addition, all TKIs exhibit additional off-target effects on kinases like PDGF-R and c-FMS which are involved in the regulation of bone metabolis...
Conference Paper
Background Treatment of chronic myeloid leukemia (CML) by tyrosine kinase inhibitors (TKIs, e.g. imatinib, dasatinib) can result in cardiac failure as these drugs exert off-target effects via so far ill-defined mechanisms. Especially in pediatric patients long-term drug exposure is of great concern as this cohort may require life-long treatment for...
Conference Paper
Introduction Imatinib (IM) front-line treatment impressively improved survival of children with chronic myeloid leukemia (CML). In contrast to adult CML, specific scoring systems predicting the treatment response in individual pediatric patients (pts) are still lacking. Here we analyzed a cohort of pediatric pts with CML applying the established pr...
Article
Background Treatment of chronic myeloid leukemia (CML) by tyrosine kinase inhibitors (TKIs, e.g. imatinib, dasatinib) can result in cardiac failure as these drugs exert off-target effects via so far ill-defined mechanisms. Especially in pediatric patients long-term drug exposure is of great concern as this cohort may require life-long treatment for...
Article
Background Tyrosine kinase inhibitors (TKIs) such as imatinib (IMA), dasatinib (DASA), and bosutinib (BOSU) inhibit the oncogenic BCR-ABL tyrosine kinase in patients with chronic myeloid leukemia (CML). In addition, all TKIs exhibit additional off-target effects on kinases like PDGF-R and c-FMS which are involved in the regulation of bone metabolis...
Article
Chronic myeloid leukemia (CML) occurring in children and adolescents is associated with a number of clinical and molecular features that differ from the correspondent disease in patients in older age. Detailed molecular analyses of the genomic BCR-ABL1 breakpoints in a cohort of 60 pediatric individuals from the German CML-paed I and CML-paed II tr...
Article
Chronic myeloid leukemia (CML) is a rare malignancy in children and is mostly diagnosed in the chronic phase (CP). In adults, the five-year overall survival rate is 89% for patients on Imatinib and disease progression occurs in 1-3% per year (Druker 2006). Once a blast crisis (BC) has occurred, treatment options are limited with a median survival o...
Article
Introduction Imatinib (IM) front-line treatment impressively improved survival of children with chronic myeloid leukemia (CML). In contrast to adult CML, specific scoring systems predicting the treatment response in individual pediatric patients (pts) are still lacking. Here we analyzed a cohort of pediatric pts with CML applying the established pr...
Article
Full-text available
Background Bosutinib is a third-generation dual tyrosine kinase inhibitor (TKI) inhibiting Abl and Src kinases. It was developed to act on up-regulated tyrosine kinases (TKs) like BCR-ABL in Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) when resistance to first- and second-generation TKIs developed. However, first- and secon...
Conference Paper
Background: In Ph+ chronic myeloid leukemia the up-regulated BCR-ABL1 tyrosine kinase (TK) is the major target of TK-inhibitors (TKI) like imatinib and dasatinib. Bosutinib is a third generation dual TKI – developed to overcome resistance to first and second generation TKIs – inhibiting Abl and also Src kinases. However, first and second generation...
Conference Paper
Background: TKI treatment can result in cardiac failure as these drugs exert off-target effects via so far ill-defined mechanisms. Long-term exposure is of great concern in pediatric patients which may require life-long treatment for diseases like chronic myeloid leukemia. We here investigated the impact of prolonged dasatinib exposure on the growi...