Dr. Michel A. Nederlof Profile

Dr. Michel A. Nederlof

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Publications (5)

SPIE Journal Paper | 22 May 2020 Open Access

Oligonucleotide conjugated antibodies permit highly multiplexed immunofluorescence for future use in clinical histopathology

Nathan McMahon, Jocelyn A. Jones, Sunjong Kwon, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

JBO, Vol. 25, Issue 05, 056004, (May 2020) https://doi.org/10.1117/12.10.1117/1.JBO.25.5.056004

KEYWORDS: Tissues, Multiplexing, Breast cancer, Luminescence, Visualization, Ultraviolet radiation, Breast, Cancer, Tumors, Proteins

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Proceedings Article | 19 February 2020 Paper

Fluorescent imaging technologies for in situ measurement of drug target engagement and cell signaling pathways

Nathan McMahon, Allison Solanki, Jocelyn Jones, Sunjong Kwon, Young-Hwan Chang, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

Proceedings Volume 11219, 112190O (2020) https://doi.org/10.1117/12.2546320

KEYWORDS: Tissues, Tumors, Resistance, Cancer, Proteins, Imaging spectroscopy, Visualization, Oncology, Multiplexing

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Successful cancer treatment continues to elude modern medicine and its arsenal of therapeutic strategies. Therapy resistance is driven by significant tumor heterogeneity, complex interactions between malignant, microenvironmental and immune cells and cross talk between signaling pathways. Advances in molecular characterization technologies such as next generation sequencing have helped unravel this network of interactions and identify druggable therapeutic targets. Tyrosine kinase inhibitors (TKI) are a class of drugs seeking to inhibit signaling pathways critical to sustaining proliferative signaling, resisting cell death, and the other hallmarks of cancer. While tumors may initially respond to TKI therapy, disease progression is near universal due to mechanisms of acquired resistance largely involving cellular signaling pathway reprogramming. With the ultimate goal of improved TKI therapeutic efficacy our group has developed intracellular paired agent imaging (iPAI) to quantify drug target interactions and oligonucleotide conjugated antibody (Ab-oligo) cyclic immunofluorescence (cycIF) imaging to characterize perturbed signaling pathways in response to therapy. iPAI uses spectrally distinct, fluorescently labeled targeted and untargeted drug derivatives, correcting for non-specific drug distribution and facilitating quantitative assessment of the drug binding before and after therapy. Ab-oligo cycIF exploits in situ hybridization of complementary oligonucleotides for biomarker labeling while oligonucleotide modifications facilitate signal removal for sequential rounds of fluorescent tagging and imaging. Aboligo CycIF is capable of generating extreme multi-parametric images for quantifying total and phosphorylated protein expression to quantify protein activation, expression, and spatial distribution. Together iPAI and Ab-oligo cycIF can be applied to interrogate drug uptake and target binding as well as changes to heterogenous cell populations within tumors that drive variable therapeutic responses in patients.

Proceedings Article | 4 March 2019 Presentation + Paper

Signal removal methods for highly multiplexed immunofluorescent staining using antibody conjugated oligonucleotides

Nathan McMahon, Jocelyn Jones, Jennifer Eng, Sunjong Kwon, Young-Hwan Chang, Guillaume Thibault, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

Proceedings Volume 10881, 108810X (2019) https://doi.org/10.1117/12.2510573

KEYWORDS: Tissues, Multiplexing, Luminescence, Ultraviolet radiation, Cancer, Tumors, Tissue optics, Genomics, Bioalcohols, Microscopes

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Proceedings Article | 10 May 1996 Paper

Automated interactive microscopy: measuring and manipulating the chemical and molecular dynamics of cells and tissues

D. Lansing Taylor, Lowell Harris, R. DeBiasio, Scott Fahlman, Daniel Farkas, Frederick Lanni, Michel Nederlof, Albert Gough

Proceedings Volume 2678, (1996) https://doi.org/10.1117/12.239522

KEYWORDS: Microscopes, Microscopy, Luminescence, Cameras, Image processing, Imaging systems, Human-machine interfaces, Data acquisition, Image resolution, 3D image processing

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Proceedings Article | 1 May 1991 Paper

Knowledge-driven image analysis of cell structures

Michel Nederlof, Andrew Witkin, D. Lansing Taylor

Proceedings Volume 1428, (1991) https://doi.org/10.1117/12.44145

KEYWORDS: Image processing, 3D image processing, Image analysis, Image segmentation, Microscopy, 3D acquisition, Data acquisition, Imaging systems, Microscopes, Luminescence

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