Publications

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64 Publications visible to you, out of a total of 64
Optical Detection of Interleukin-6 Using Liquid Janus Emulsions Using Hyperthermophilic Affinity Proteins.

Abstract (Expand)

When equal volumes of two immiscible liquids are mixed (e.g., a hydrocarbon and a fluorocarbon), Janus droplets can form in an aqueous solution. In a gravity-aligned Janus droplet, the boundary between … the two phases is flat and thus optically transparent when viewed from above. When tipped due to interactions with an analyte (i.e., agglutination), the resulting change in refraction and reflection yields an optical signal that can be detected and quantified. This study reports the detection and quantitation of interleukin-6 (IL-6) using emulsions functionalized at the hydrocarbon:aqueous interface with engineered proteins that bind IL-6 at high affinity and specificity. Hyperthermophilic affinity proteins (rcSso7d) are derived from thermophiles, giving them excellent thermal stability. Two rcSso7d affinity protein variants were synthesized with a noncanonical azide-functionalized amino acid to enable click chemistry to novel polymeric anchors embedded in the hydrocarbon phase. The two binding proteins recognize different epitopes, enabling the detection of both monomeric and dimeric IL-6 via agglutination. It is noteworthy that the rsSso7d protein variants, in addition to having superior thermal stability and facile recombinant synthesis in E. coli, show superior performance when compared to commercial antibodies for IL-6.

Authors: M. Chen, E. I. Corless, B. P. Engelward, T. M. Swager

Date Published: 3rd Sep 2024

Publication Type: Journal Article

Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Abstract (Expand)

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor … prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-beta (CSF1R/CCR2/TGF-beta Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.

Authors: H. T. Nguyen, E. L. Kan, M. Humayun, N. Gurvich, G. S. Offeddu, Z. Wan, M. F. Coughlin, D. C. Renteria, A. Loew, S. Wilson, C. Zhang, V. Vu, S. W. L. Lee, S. L. Tan, D. Barbie, J. Hsu, M. R. Gillrie, R. D. Kamm

Date Published: 3rd Sep 2024

Publication Type: Journal Article

Utilizing convolutional neural networks for discriminating cancer and stromal cells in three-dimensional cell culture images with nuclei counterstain.

Abstract (Expand)

SIGNIFICANCE: Accurate cell segmentation and classification in three-dimensional (3D) images are vital for studying live cell behavior and drug responses in 3D tissue culture. Evaluating diverse cell … populations in 3D cell culture over time necessitates non-toxic staining methods, as specific fluorescent tags may not be suitable, and immunofluorescence staining can be cytotoxic for prolonged live cell cultures. AIM: We aim to perform machine learning-based cell classification within a live heterogeneous cell culture population grown in a 3D tissue culture relying only on reflectance, transmittance, and nuclei counterstained images obtained by confocal microscopy. APPROACH: In this study, we employed a supervised convolutional neural network (CNN) to classify tumor cells and fibroblasts within 3D-grown spheroids. These cells are first segmented using the marker-controlled watershed image processing method. Training data included nuclei counterstaining, reflectance, and transmitted light images, with stained fibroblast and tumor cells as ground-truth labels. RESULTS: Our results demonstrate the successful marker-controlled watershed segmentation of 84% of spheroid cells into single cells. We achieved a median accuracy of 67% (95% confidence interval of the median is 65-71%) in identifying cell types. We also recapitulate the original 3D images using the CNN-classified cells to visualize the original 3D-stained image's cell distribution. CONCLUSION: This study introduces a non-invasive toxicity-free approach to 3D cell culture evaluation, combining machine learning with confocal microscopy, opening avenues for advanced cell studies.

Authors: H. T. Nguyen, N. Pietraszek, S. E. Shelton, K. Arthur, R. D. Kamm

Date Published: 26th Aug 2024

Publication Type: Journal Article

Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis

Abstract

Not specified

Authors: Edward B. Irvine, Angel Nikolov, Mehak Z. Khan, Joshua M. Peters, Richard Lu, Jaimie Sixsmith, Aaron Wallace, Esther van Woudenbergh, Sally Shin, Wiktor Karpinski, Jeff C. Hsiao, Arturo Casadevall, Bryan D. Bryson, Lisa Cavacini, Patricia S. Grace, Galit Alter, Sarah M. Fortune

Date Published: 22nd Aug 2024

Publication Type: Journal Article

Utilizing convolutional neural networks for discriminating cancer and stromal cells in three-dimensional cell culture images with nuclei counterstain

Abstract

Not specified

Authors: Huu Tuan Nguyen, Nicholas Pietraszek, Sarah E. Shelton, Kwabena Arthur, Roger D. Kamm

Date Published: 1st Aug 2024

Publication Type: Journal Article

Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion.

Abstract (Expand)

Metastasis, the leading cause of cancer-related deaths, involves a complex cascade of events, including extravasation. Despite extensive research into metastasis, the mechanisms underlying extravasation … remain unclear. Molecular targeted therapies have advanced cancer treatment, yet their efficacy is limited, prompting exploration into novel therapeutic targets. Here, we showed the association of polyploidy in MDA-MB-231 breast cancer cells and their extravasation, using microfluidic systems to reproduce the in vivo microvascular environment. We observed enhanced extravasation in polyploid cells alongside upregulated expression of genes involved in cell-substrate adhesion and cell mechanical dynamics. These findings offer insights into the relationship between polyploidy and extravasation, highlighting potential targets for cancer therapy.

Authors: S. Hirose, T. Osaki, R. D. Kamm

Date Published: 2nd Jul 2024

Publication Type: Journal Article

Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis

Abstract

Not specified

Authors: Meng Sun, Jolie M. Phan, Nathan S. Kieswetter, Huang Huang, Krystle K. Q. Yu, Malisa T. Smith, Yiran E. Liu, Chuangqi Wang, Sanjana Gupta, Gerlinde Obermoser, Holden Terry Maecker, Akshaya Krishnan, Sundari Suresh, Neha Gupta, Mary Rieck, Peter Acs, Mustafa Ghanizada, Shin-Heng Chiou, Purvesh Khatri, W. Henry Boom, Thomas R. Hawn, Catherine M. Stein, Harriet Mayanja-Kizza, Mark M. Davis, Chetan Seshadri

Date Published: 1st Jul 2024

Publication Type: Journal Article

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