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Article ; Online: Systems biology of B cells in COVID-19.

Woodruff, Matthew C / Faliti, Caterina E / Sanz, Ignacio

2024 Volume 72, Page(s) 101875

Abstract: The integration of multi-'omic datasets into complex systems-wide assessments has become a mainstay in immunologic investigation. This focus on high-dimensional data collection and analysis was on full display in the investigation of COVID-19, the ... ...

Abstract	The integration of multi-'omic datasets into complex systems-wide assessments has become a mainstay in immunologic investigation. This focus on high-dimensional data collection and analysis was on full display in the investigation of COVID-19, the respiratory illness resulting from infection by the novel coronavirus SARS-CoV-2. Particularly in the area of B cell biology, tremendous efforts in both cellular and serologic investigation have resulted in an increasingly detailed mapping of the coordinated effector, memory, and antibody secreting cell responses that underpin the development of humoral immunity in response to primary viral infection. Further, the rapid development and deployment of effective vaccines has allowed for the assessment of developing memory responses across a wide variety of immune contexts, including in patients with compromised immune function. The result has been a period of rapid gains in the understanding of B cell biology unrestricted to the study of COVID-19. Here, we outline the systems-level technologies that have been routinely implemented in these investigations throughout the pandemic, and discuss how their use has led to clear and applicable gains in pursuance of the amelioration of human infectious disease and beyond.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; B-Lymphocytes ; Immunity, Humoral ; Systems Biology ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1018141-6
ISSN	1096-3618 ; 1044-5323
ISSN (online)	1096-3618
ISSN	1044-5323
DOI	10.1016/j.smim.2024.101875
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Article ; Online: Knife's edge: Balancing immunogenicity and reactogenicity in mRNA vaccines.

Lee, Jisun / Woodruff, Matthew C / Kim, Eui Ho / Nam, Jae-Hwan

Experimental & molecular medicine

2023 Volume 55, Issue 7, Page(s) 1305–1313

Abstract: Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of therapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were developed and approved in record-breaking time, ... ...

Abstract	Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of therapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were developed and approved in record-breaking time, revolutionizing the vaccine development landscape. Although first-generation COVID-19 mRNA vaccines have demonstrated over 90% efficacy, alongside strong immunogenicity in humoral and cell-mediated immune responses, their durability has lagged compared to long-lived vaccines, such as the yellow fever vaccine. Although worldwide vaccination campaigns have saved lives estimated in the tens of millions, side effects, ranging from mild reactogenicity to rare severe diseases, have been reported. This review provides an overview and mechanistic insights into immune responses and adverse effects documented primarily for COVID-19 mRNA vaccines. Furthermore, we discuss the perspectives of this promising vaccine platform and the challenges in balancing immunogenicity and adverse effects.
MeSH term(s)	Humans ; COVID-19/prevention & control ; Pandemics ; Pentaerythritol Tetranitrate ; RNA, Messenger/genetics ; mRNA Vaccines
Chemical Substances	Pentaerythritol Tetranitrate (10L39TRG1Z) ; RNA, Messenger ; mRNA Vaccines
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-023-00999-x
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Zs.A 4775: Show issues

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Article ; Online: Colorectal Malignancy Complicated by Arterioenteric Fistula.

Woodruff, Grant C / Yap, Chelsea A / Kazaleh, Matthew S / Crandall, Marie L / Zhang, Jeanette

The American surgeon

2023 Volume 89, Issue 9, Page(s) 3844–3846

Abstract: Arterioenteric fistulas (AEF) are rare and devastating complications of colorectal/pelvic malignancies. These fistulas can be seen following neoadjuvant or adjuvant therapy but are exceptionally rare de novo. The reported incidence of AEF is less than 1% ...

Abstract	Arterioenteric fistulas (AEF) are rare and devastating complications of colorectal/pelvic malignancies. These fistulas can be seen following neoadjuvant or adjuvant therapy but are exceptionally rare de novo. The reported incidence of AEF is less than 1% and iliac artery-enteric fistulas make up less than .1% of all AEF. Here we present a patient in hemorrhagic shock secondary to an advanced colorectal malignancy without adjuvant therapies with local invasion of the right external iliac artery. Following initial resuscitation and hemorrhage control with coil embolization, definitive control with ligation and excision of the involved artery, end colostomy, and ureteral stent placement was achieved. It is important to consider malignancy as the source of lower gastrointestinal bleeds, especially in elderly patients without current colonoscopy studies. The management of this unfortunate diagnosis often involves a multidisciplinary approach with early and frequent goals of care discussions.
MeSH term(s)	Humans ; Aged ; Intestinal Fistula/etiology ; Intestinal Fistula/surgery ; Intestinal Fistula/diagnosis ; Iliac Artery ; Blood Vessel Prosthesis/adverse effects ; Colorectal Neoplasms/complications ; Aorta, Abdominal ; Vascular Fistula/complications ; Vascular Fistula/surgery
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
DOI	10.1177/00031348231173954
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Article ; Online: Majority of human circulating IgG plasmablasts stop blasting in a cell-free pro-survival culture.

Nguyen, Doan C / Saney, Celia / Hentenaar, Ian T / Cabrera-Mora, Monica / Capric, Violeta / Woodruff, Matthew C / Andrews, Joel / Lonial, Sagar / Sanz, Ignacio / Lee, F Eun-Hyung

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3616

Abstract: Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, ... ...

Abstract	Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be "blasting" or proliferative. In this study, we find > 95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4 h or 24 h labeling. In contrast, < 5% BM LLPC in culture are Ki-67
MeSH term(s)	Humans ; Plasma Cells/metabolism ; Ki-67 Antigen ; Bone Marrow/metabolism ; Immunoglobulin G ; Antigens, CD19/metabolism
Chemical Substances	Ki-67 Antigen ; Immunoglobulin G ; Antigens, CD19
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-53977-2
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Article ; Online: Response under pressure: deploying emerging technologies to understand B-cell-mediated immunity in COVID-19.

Woodruff, Matthew C / Nguyen, Doan C / Faliti, Caterina E / Saini, Ankur Singh / Lee, F Eun-Hyung / Sanz, Ignacio

Nature methods

2022 Volume 19, Issue 4, Page(s) 387–391

MeSH term(s)	Adaptive Immunity ; COVID-19 ; Humans ; Immunity, Cellular ; SARS-CoV-2
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-022-01450-1
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Article: Majority of human circulating plasmablasts stop blasting: A probable misnomer.

Nguyen, Doan C / Saney, Celia / Hentenaar, Ian T / Cabrera-Mora, Monica / Woodruff, Matthew C / Andrews, Joel / Lonial, Sagar / Sanz, Ignacio / Lee, F Eun-Hyung

bioRxiv : the preprint server for biology

2023

Abstract	Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be "blasting" or proliferative. In this study, we find >95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4h or 24h labeling. In contrast, <5% BM LLPC in culture are Ki-67
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.10.557057
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Article ; Online: COVID-19 and plasma cells: Is there long-lived protection?

Nguyen, Doan C / Lamothe, Pedro A / Woodruff, Matthew C / Saini, Ankur S / Faliti, Caterina E / Sanz, Ignacio / Lee, Frances Eun-Hyung

Immunological reviews

2022 Volume 309, Issue 1, Page(s) 40–63

Abstract: Infection with SARS-CoV-2, the etiology of the ongoing COVID-19 pandemic, has resulted in over 450 million cases with more than 6 million deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from ... ...

Abstract	Infection with SARS-CoV-2, the etiology of the ongoing COVID-19 pandemic, has resulted in over 450 million cases with more than 6 million deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from long-lived plasma cells (LLPC) are the mainstay of most effective vaccines. However, ending the pandemic has been hampered by the lack of long-lived immunity after infection or vaccination. Although immunizations offer protection from severe disease and hospitalization, breakthrough infections still occur, most likely due to new mutant viruses and the overall decline of neutralizing antibodies after 6 months. Here, we review the current knowledge of B cells, from extrafollicular to memory populations, with a focus on distinct plasma cell subsets, such as early-minted blood antibody-secreting cells and the bone marrow LLPC, and how these humoral compartments contribute to protection after SARS-CoV-2 infection and immunization.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Immunity, Humoral ; Pandemics/prevention & control ; Plasma Cells ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-07-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13115
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Article ; Online: Model-based data analysis of tissue growth in thin 3D printed scaffolds.

Browning, Alexander P / Maclaren, Oliver J / Buenzli, Pascal R / Lanaro, Matthew / Allenby, Mark C / Woodruff, Maria A / Simpson, Matthew J

Journal of theoretical biology

2021 Volume 528, Page(s) 110852

Abstract: Tissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in more biologically realistic geometries than that allowed by traditional 2D cell culture. Cell proliferation and migration in these experiments ... ...

Abstract	Tissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in more biologically realistic geometries than that allowed by traditional 2D cell culture. Cell proliferation and migration in these experiments have yet to be explicitly characterised, limiting the ability of experimentalists to determine the effects of various experimental conditions, such as scaffold geometry, on cell behaviour. We consider tissue growth by osteoblastic cells in melt electro-written scaffolds that comprise thin square pores with sizes that were deliberately increased between experiments. We collect highly detailed temporal measurements of the average cell density, tissue coverage, and tissue geometry. To quantify tissue growth in terms of the underlying cell proliferation and migration processes, we introduce and calibrate a mechanistic mathematical model based on the Porous-Fisher reaction-diffusion equation. Parameter estimates and uncertainty quantification through profile likelihood analysis reveal consistency in the rate of cell proliferation and steady-state cell density between pore sizes. This analysis also serves as an important model verification tool: while the use of reaction-diffusion models in biology is widespread, the appropriateness of these models to describe tissue growth in 3D scaffolds has yet to be explored. We find that the Porous-Fisher model is able to capture features relating to the cell density and tissue coverage, but is not able to capture geometric features relating to the circularity of the tissue interface. Our analysis identifies two distinct stages of tissue growth, suggests several areas for model refinement, and provides guidance for future experimental work that explores tissue growth in 3D printed scaffolds.
MeSH term(s)	Cell Proliferation ; Data Analysis ; Porosity ; Printing, Three-Dimensional ; Tissue Engineering ; Tissue Scaffolds
Language	English
Publishing date	2021-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2972-5
ISSN	1095-8541 ; 0022-5193
ISSN (online)	1095-8541
ISSN	0022-5193
DOI	10.1016/j.jtbi.2021.110852
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Article ; Online: A quantitative analysis of cell bridging kinetics on a scaffold using computer vision algorithms.

Lanaro, Matthew / Mclaughlin, Maximilion P / Simpson, Matthew J / Buenzli, Pascal R / Wong, Cynthia S / Allenby, Mark C / Woodruff, Maria A

Acta biomaterialia

2021 Volume 136, Page(s) 429–440

Abstract: Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of ... ...

Abstract	Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of their local environment is needed. Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro scaffold model to study cellular spatial-temporal kinetics. These scaffolds were paired with custom computer vision algorithms to investigate cell nuclei, cell membrane actin and scaffold fibres over different pore sizes (200-600 µm) and time points (28 days). We find that cells proliferated much faster in the smaller (200 µm) pores which halved the time until confluence versus larger (500 and 600 µm) pores. Our analysis of stained actin fibres revealed that cells were highly aligned to the fibres and the leading edge of the pore filling front, and we found that cells behind the leading edge were not aligned in any particular direction. This study provides a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model to inform the design of more effective synthetic tissue engineering scaffolds for tissue regeneration. STATEMENT OF SIGNIFICANCE: Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro model to study cellular spatial-temporal kinetics to provide a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model. The insights presented in this work help to inform the design of more effective synthetic tissue engineering scaffolds by reducing cell culture time; which is valuable information for the implant or lab-grown-meat industries.
MeSH term(s)	Algorithms ; Computers ; Kinetics ; Porosity ; Printing, Three-Dimensional ; Tissue Engineering ; Tissue Scaffolds
Language	English
Publishing date	2021-09-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2021.09.042
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Article ; Online: Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.

Chen, Weirong / Hong, So-Hee / Jenks, Scott A / Anam, Fabliha A / Tipton, Christopher M / Woodruff, Matthew C / Hom, Jennifer R / Cashman, Kevin S / Faliti, Caterina Elisa / Wang, Xiaoqian / Kyu, Shuya / Wei, Chungwen / Scharer, Christopher D / Mi, Tian / Hicks, Sakeenah / Hartson, Louise / Nguyen, Doan C / Khosroshahi, Arezou / Lee, Saeyun /

Wang, Youliang / Bugrovsky, Regina / Ishii, Yusho / Lee, F Eun-Hyung / Sanz, Ignacio

Nature communications

2024 Volume 15, Issue 1, Page(s) 1899

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we ... ...

Abstract	Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19
MeSH term(s)	Humans ; Cytokines ; Transcriptome ; Lupus Erythematosus, Systemic/genetics ; Antibody-Producing Cells ; Autoimmune Diseases
Chemical Substances	Cytokines
Language	English
Publishing date	2024-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46053-w
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