Targeting BCR-ABL and JAK2 in Ph+ ALL

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Mouse Systems Genetics as a Prelude to Precision Medicine

Johan Auwerx, Hao Li

Mouse models have been instrumental in understanding human disease biology and proposing possible new treatments. The precise control of the environment and genetic composition of mice allows more rigorous observations, but limits the generalizability and ...

2020

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Anja Irmisch, Oliver Hantschel, Jörg Hülsken

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ ...

2019

Pharmacokinetics and biodistribution study of self-assembled Gd-micelles demonstrating blood-pool contrast enhancement for MRI

Lothar Helm, Yohan Van de Looij

Magnetic resonance angiography (MRA) requires the use of contrast agents (CAs) to enable accurate diagnosis. There are currently no CAs on the market with appropriate pharmacokinetic (PK) parameters, namely long persistence in the blood, that can be easily ...

2019

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

We present a rapid and high-throughput yeast and flow cytometry based method for predicting kinase inhibitor resistance mutations and determining kinase peptide substrate specificity. Despite the widespread success of targeted kinase inhibitors as cancer t ...

AMER CHEMICAL SOC2019

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Berna Ayse Özkale Edelmann, Christina Myra Tringides

Mesenchymal stem cell (MSC) therapies demonstrate particular promise in ameliorating diseases of immune dysregulation but are hampered by short in vivo cell persistence and inconsistencies in phenotype. Here, we demonstrate that biomaterial encapsulation i ...

National Academy of Sciences2019

Label-free Bacteria Quantification in Blood Plasma by a Bioprinted Microarray Based Interferometric Point-of-Care Device

Hatice Altug, Filiz Yesilköy, Alexander Belushkin

Existing clinical methods for bacteria detection lack speed, sensitivity, and, importantly, point-of-care (PoC) applicability. Thus, finding ways to push the sensitivity of clinical PoC biosensing technologies is crucial. Here we report a portable PoC devi ...

AMER CHEMICAL SOC2019

Targeted antibody and cytokine cancer immunotherapies through collagen affinity

Jeffrey Alan Hubbell, Melody Swartz, Lambert Charles François Potin

Cancer immunotherapy with immune checkpoint inhibitors (CPIs) and interleukin-2 (IL-2) has demonstrated clinical efficacy but is frequently accompanied with severe adverse events caused by excessive and systemic immune system activation. Here, we addressed ...

AMER ASSOC ADVANCEMENT SCIENCE2019

Development of cyclic peptide inhibitors of coagulation factor XIa for safer anticoagulation

Vanessa Carle

Hemostasis is a complex physiological process responsible for the prevention of blood loss caused by vascular injury. The dysregulation of this delicate mechanism can lead to thromboembolic diseases, the leading cause of death worldwide. Anticoagulants are ...

EPFL2019

Toward Microfluidic Label-Free Isolation and Enumeration of Circulating Tumor Cells from Blood Samples

Philippe Renaud, Margaux Catherine Marie Duchamp, Benoît Xavier Emmanuel Desbiolles, Camille Alice Raillon

The isolation, analysis, and enumeration of circulating tumor cells (CTCs) from cancer patient blood samples are a paradigm shift for cancer patient diagnosis, prognosis, and treatment monitoring. Most methods used to isolate and enumerate these target cel ...

WILEY2019

Microdevice-integrated immunoassays for Point-of-Care Therapeutic Drug Monitoring

Elena-Diana Bojescu

A significant number of drugs exhibit narrow therapeutic windows and high inter-individual pharmacokinetic variability. In such cases, Therapeutic Drug Monitoring (TDM) is compulsory in order to optimize the efficacy of the drug while avoiding adverse effe ...

EPFL2018

Semisynthetic sensor proteins enable metabolic assays at the point of care

Kai Johnsson, Rudolf Griss, Qiuliyang Yu, Lin Xue, Julien Hiblot

Monitoring metabolites at the point of care could improve the diagnosis and management of numerous diseases. Yet for most metabolites, such assays are not available. We introduce semisynthetic, light-emitting sensor proteins for use in paper-based metaboli ...

American Association for the Advancement of Science2018

Towards Elucidating the Mechanism of Action of Biguanides

Nicolas Peter Goeldel

Diabetes type 2 patients are insensitive to insulin, a condition that leads to reduced glucose uptake by cells and, subsequently, to high concentration of glucose in the blood. For 60 years, biguanides have been one of the few effective therapeutics in red ...

EPFL2018