- Hematopoietic Stem Cell Transplantation
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Gene Regulatory Network Analysis
- Erythrocyte Function and Pathophysiology
- Microfluidic and Bio-sensing Technologies
- CRISPR and Genetic Engineering
- Cell Image Analysis Techniques
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Microfluidic and Capillary Electrophoresis Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Platelet Disorders and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Hemoglobinopathies and Related Disorders
St. Jude Children's Research Hospital
2022-2025
University of Tennessee Health Science Center
2023-2024
ETH Zurich
2015-2024
University of Tennessee at Knoxville
2024
Children's Research Hospital
2023
Board of the Swiss Federal Institutes of Technology
2016-2021
Victoria University of Wellington
2019
Helmholtz Zentrum München
2011-2018
Hematopoietic stem cells (HSCs) are capable of entering the cell cycle to replenish blood system in response inflammatory cues; however, excessive proliferation chronic inflammation can lead either HSC attrition or expansion. The mechanism(s) that limit and expansion triggered by signals poorly defined. Here, we show long-term HSCs (HSCLT) rapidly repress protein synthesis genes following treatment with proinflammatory cytokine interleukin (IL)-1. This gene program is associated activation...
Quantitative large-scale cell microscopy is widely used in biological and medical research. Such experiments produce huge amounts of image data thus require automated analysis. However, detection outlines (cell segmentation) typically challenging due to, e.g. high densities, cell-to-cell variability low signal-to-noise ratios.Here, we evaluate accuracy speed various state-of-the-art approaches for segmentation light images using real synthetic data. The results vary between datasets show...
Abstract Liquid handling robots have the potential to automate many procedures in life sciences. However, they are not widespread use academic settings, where funding, space and maintenance specialists usually limiting. In addition, current require lengthy programming by incompatible with most laboratories constantly changing small-scale projects. Here, we present Pipetting Helper Imaging Lid (PHIL), an inexpensive, small, open-source personal liquid robot. It is designed for inexperienced...
Abstract Sickle Cell Disease (SCD) is a blood disorder affecting millions worldwide. Emerging evidence reveals that SCD pathophysiology increases risk of myeloid malignancies and hematopoietic stem cell (HSC) dysfunction, possibly due to pathological stress on bone marrow. To investigate this further, we interrogated mice individuals with observed extended cycle times, oxidative stress, DNA damage, senescence, dysregulation molecular programs associated these processes in marrow progenitor...
Molecular programs initiating cell fate divergence (CFD) are difficult to identify. Current approaches usually compare cells long after CFD initiation, therefore missing molecular changes at its start. Ideally, single that differ in their program but otherwise identical compared early CFD. This is possible diverging sister cells, which were until mother's division and thus mainly properties. In asymmetrically dividing divergent daughter fates prospectively committed during division, sisters...
Dynamic environments determine cell fate decisions and function. Understanding the relationship between extrinsic signals on cellular responses requires ability to dynamically change environmental inputs in vitro, while continuously observing individual cells over extended periods of time. This is challenging for nonadherent cells, such as hematopoietic stem progenitor because media flow displaces disturbs preventing culture tracking single cells. Here, we present a programmable microfluidic...
Embryonic stem cells (ESCs) display heterogeneous expression of pluripotency factors such as Nanog when cultured with serum and leukemia inhibitory factor (LIF). In contrast, dual inhibition the signaling kinases GSK3 MEK (2i) converts ESC cultures into a state more uniform high expression. However, it is so far unclear whether 2i acts through an inductive or selective mechanism. Here, we use continuous time-lapse imaging to quantify dynamics death, proliferation, in mouse ESCs after...
Rapid clonal expansion of antigen-specific T cells is a fundamental feature adaptive immune responses. It enables the outgrowth an individual cell into thousands descendants that diversify short-lived effectors and long-lived memory cells. Clonal thought to be programmed upon priming single naive then executed by homogenously fast divisions all its descendants. However, actual speed in such emerging "T family" has never been measured with single-cell resolution. Here, we utilize continuous...
Abstract Molecular regulation of cell fate decisions underlies health and disease. To identify molecules that are active or regulated during a decision, not before after, the decision time point is crucial. However, markers usually delayed therefore unknown. Fortunately, dividing cells induce temporal correlations in their progeny, which allow for retrospective inference point. We present computational method to infer points from correlated marker signals genealogies apply it differentiating...