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3. Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI)

Author

Adair, Jennifer E., Androski, Lindsay, Bayigga, Lois, Bazira, Deus, Brandon, Eugene, Dee, Lynda, Deeks, Steven, Draz, Mohamed, Dubé, Karine, Dybul, Mark, Gurkan, Umut, Harlow, Evelyn, Kityo, Cissy, Louella, Michael, Malik, Punam, Mathews, Vikram, McKemey, Adrian, Mugerwa, Henry, Muyanja, Daniel, Olayiwola, Olabimpe, Orentas, Rimas J., Popovski, Alex, Sheehy, Jeff, Ssali, Francis, Nsubuga, Moses Supercharger, Tisdale, John F., Verhoeyen, Els, and Dropulić, Boro

Published
2023
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4. Beta-defensin index: A functional biomarker for oral cancer detection

Author

Ghosh, Santosh K., Man, Yuncheng, Fraiwan, Arwa, Waters, Christopher, McKenzie, Crist, Lu, Cheng, Pfau, David, Kawsar, Hameem, Bhaskaran, Natarajan, Pandiyan, Pushpa, Jin, Ge, Briggs, Farren, Zender, Chad C., Rezaee, Rod, Panagakos, Fotinos, Thuener, Jason E., Wasman, Jay, Tang, Alice, Qari, Hiba, Wise-Draper, Trisha, McCormick, Thomas S., Madabhushi, Anant, Gurkan, Umut A., and Weinberg, Aaron

Published
2024
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9. Inhibition of Band 3 tyrosine phosphorylation: a new mechanism for treatment of sickle cell disease.

Author

Noomuna, Panae, Risinger, Mary, Zhou, Sitong, Seu, Katie, Man, Yuncheng, An, Ran, Sheik, Daniel A, Wan, Jiandi, Little, Jane A, Gurkan, Umut A, Turrini, Francesco M, Kalfa, Theodosia, and Low, Philip S

Subjects
Endothelium, Vascular, Erythrocyte Membrane, Erythrocytes, Abnormal, Plasma, Humans, Anemia, Sickle Cell, Sickle Cell Trait, beta-Thalassemia, Oxygen, Phosphotyrosine, Anion Exchange Protein 1, Erythrocyte, Hemoglobin, Sickle, Protein Kinase Inhibitors, Drug Evaluation, Preclinical, Cell Adhesion, Protein Processing, Post-Translational, Oxidative Stress, Phosphorylation, Erythrocyte Deformability, Cell-Derived Microparticles, Imatinib Mesylate, anion exchanger 1, erythrocyte membrane, haemoglobinopathy, sickle cell disease, tyrosine phosphorylation, Sickle Cell Disease, Rare Diseases, Pain Research, Hematology, Clinical Research, Cardiorespiratory Medicine and Haematology, Immunology
Abstract

Many hypotheses have been proposed to explain how a glutamate to valine substitution in sickle haemoglobin (HbS) can cause sickle cell disease (SCD). We propose and document a new mechanism in which elevated tyrosine phosphorylation of Band 3 initiates sequelae that cause vaso-occlusion and the symptoms of SCD. In this mechanism, denaturation of HbS and release of heme generate intracellular oxidants which cause inhibition of erythrocyte tyrosine phosphatases, thus permitting constitutive tyrosine phosphorylation of Band 3. This phosphorylation in turn induces dissociation of the spectrin-actin cytoskeleton from the membrane, leading to membrane weakening, discharge of membrane-derived microparticles (which initiate the coagulation cascade) and release of cell-free HbS (which consumes nitric oxide) and activates the endothelium to express adhesion receptors). These processes promote vaso-occlusive events which cause SCD. We further show that inhibitors of Syk tyrosine kinase block Band 3 tyrosine phosphorylation, prevent release of cell-free Hb, inhibit discharge of membrane-derived microparticles, increase sickle cell deformability, reduce sickle cell adhesion to human endothelial cells, and enhance sickle cell flow through microcapillaries. In view of reports that imatinib (a Syk inhibitor) successfully treats symptoms of sickle cell disease, we suggest that Syk tyrosine kinase inhibitors warrant repurposing as potential treatments for SCD.

Published
2020

13. Correction: Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI)

Author

Adair, Jennifer E., Androski, Lindsay, Bayigga, Lois, Bazira, Deus, Brandon, Eugene, Dee, Lynda, Deeks, Steven, Draz, Mohamed, Dubé, Karine, Dybul, Mark, Gurkan, Umut, Harlow, Evelyn, Kityo, Cissy, Louella, Michael, Malik, Punam, Mathews, Vikram, McKemey, Adrian, Mugerwa, Henry, Muyanja, Daniel, Olayiwola, Olabimpe, Orentas, Rimas J., Popovski, Alex, Sheehy, Jeff, Ssali, Francis, Nsubuga, Moses Supercharger, Tisdale, John F., Verhoeyen, Els, and Dropulić, Boro

Published
2023
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14. Reply to Kaestner et al.: Pioneering quantitative platforms for stored red blood cell assessment open the door for precision transfusion medicine

Author

Isiksacan, Ziya, primary, D’Alessandro, Angelo, additional, McKenna, David H., additional, Tessier, Shannon N., additional, Kucukal, Erdem, additional, Gokaltun, A. Aslihan, additional, William, Nishaka, additional, Sandlin, Rebecca D., additional, Bischof, John, additional, Mohandas, Narla, additional, Busch, Michael P., additional, Elbuken, Caglar, additional, Gurkan, Umut A., additional, Toner, Mehmet, additional, Acker, Jason P., additional, Yarmush, Martin L., additional, and Usta, O. Berk, additional

Published
2024
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16. Next generation microfluidics: fulfilling the promise of lab-on-a-chip technologies

Author

Gurkan, Umut A., primary, Wood, David K., additional, Carranza, Dorn, additional, Herbertson, Luke H., additional, Diamond, Scott L., additional, Du, E., additional, Guha, Suvajyoti, additional, Di Paola, Jorge, additional, Hines, Patrick C., additional, Papautsky, Ian, additional, Shevkoplyas, Sergey S., additional, Sniadecki, Nathan J., additional, Pamula, Vamsee K., additional, Sundd, Prithu, additional, Rizwan, Asif, additional, Qasba, Pankaj, additional, and Lam, Wilbur A., additional

Published
2024
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19. New voices for a better society.

Author

Diem, Stephanie J., Rittschof, Clare C., Silveyra, Patricia, Gurkan, Umut A., Reeve, Alison Boland, Najib, Dalal, and Wasson, Flannery

Subjects
ACADEMIC-industrial collaboration, HISTORICALLY Black colleges & universities, ARTIFICIAL neural networks, RADIOACTIVE waste management, COVID-19 pandemic, INDUSTRIAL engineers, CRISIS intervention (Mental health services)
Abstract

The article discusses the New Voices program established by the US National Academies of Sciences, Engineering, and Medicine (NASEM) in 2018. The program aims to bring diverse and innovative perspectives from early- and mid-career leaders to important discussions on how science, engineering, and medicine shape the global future. The program selects members through a competitive application process and supports them in enhancing scientific and policy solutions to national and global challenges. The article emphasizes the interdisciplinary nature of the program and the importance of inclusivity and diversity in scientific research and policymaking. The program has initiated various projects, including the development of an AI chatbot for organizing and sharing public health information, examining the impact of climate change on engineering design, and promoting science diplomacy and diversity in STEM fields. The program has also provided opportunities for members to engage in NASEM activities and global events, contributing to their career advancement and the advancement of science. The New Voices program is supported by the Gordon and Betty Moore Foundation, the Rutter Foundation, and the Doris Duke Charitable Foundation. [Extracted from the article]

Published
2024
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21. Motion Blur Microscopy

Author

Goreke, Utku, primary, Gonzales, Ayesha, additional, Shipley, Brandon, additional, Man, Yuncheng, additional, Wulftange, William, additional, An, Ran, additional, Hinczewski, Michael, additional, and Gurkan, Umut A, additional

Published
2023
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24. P1439: EPELEUTON, A NOVEL SYNTHETIC Ω-3 FATTY ACID, REDUCES ENDOTHELIAL ADHESION OF RED BLOOD CELLS FROM SICKLE CELL DISEASE PATIENTS UNDER PHYSIOLOGICAL FLOW CONDITIONS

Author

Hamza, Moayed, primary, Downes, Bill, additional, Federici, Chiara, additional, Braxton, Samantha, additional, Sertel, Seniye, additional, Combs, Gabrielle, additional, Andemariam, Biree, additional, Zak, John, additional, Gurkan, Umut A, additional, and Climax, John, additional

Published
2023
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26. Assessment of stored red blood cells through lab-on-a-chip technologies for precision transfusion medicine

Author

Isiksacan, Ziya, primary, D’Alessandro, Angelo, additional, Wolf, Susan M., additional, McKenna, David H., additional, Tessier, Shannon N., additional, Kucukal, Erdem, additional, Gokaltun, A. Aslihan, additional, William, Nishaka, additional, Sandlin, Rebecca D., additional, Bischof, John, additional, Mohandas, Narla, additional, Busch, Michael P., additional, Elbuken, Caglar, additional, Gurkan, Umut A., additional, Toner, Mehmet, additional, Acker, Jason P., additional, Yarmush, Martin L., additional, and Usta, O. Berk, additional

Published
2023
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27. 3D-Printed Biohybrid Robots Powered by Neuromuscular Tissue Circuits from Aplysia californica

Author

Webster, Victoria A., Young, Fletcher R., Patel, Jill M., Scariano, Gabrielle N., Akkus, Ozan, Gurkan, Umut A., Chiel, Hillel J., Quinn, Roger D., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Mangan, Michael, editor, Cutkosky, Mark, editor, Mura, Anna, editor, Verschure, Paul F.M.J., editor, Prescott, Tony, editor, and Lepora, Nathan, editor

Published
2017
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30. Decorrelation Time Mapping as an Analysis Tool for Nanobubble-Based Contrast Enhanced Ultrasound Imaging

Author

Wegierak, Dana, Cooley, Michaela B., Perera, Reshani, Wulftange, William J., Gurkan, Umut A., Kolios, Michael C., and Exner, Agata A.

Abstract

Nanobubbles (NBs; ~100–500 nm diameter) are preclinical ultrasound (US) contrast agents that expand applications of contrast enhanced US (CEUS). Due to their sub-micron size, high particle density, and deformable shell, NBs in pathological states of heightened vascular permeability (e.g. in tumors) extravasate, enabling applications not possible with microbubbles (~1000-10,000 nm diameter). A method that can separate intravascular versus extravascular NB signal is needed as an imaging biomarker for improved tumor detection. We present a demonstration of decorrelation time (DT) mapping for enhanced tumor NB-CEUS imaging. In vitro models validated the sensitivity of DT to agent motion. Prostate cancer mouse models validated in vivo imaging potential and sensitivity to cancerous tissue. Our findings show that DT is inversely related to NB motion, offering enhanced detail of NB dynamics in tumors, and highlighting the heterogeneity of the tumor environment. Average DT was high in tumor regions (~9 s) compared to surrounding normal tissue (~1 s) with higher sensitivity to tumor tissue compared to other mapping techniques. Molecular NB targeting to tumors further extended DT (11 s) over non-targeted NBs (6 s), demonstrating sensitivity to NB adherence. From DT mapping of in vivo NB dynamics we demonstrate the heterogeneity of tumor tissue while quantifying extravascular NB kinetics and delineating intra-tumoral vasculature. This new NB-CEUS-based biomarker can be powerful in molecular US imaging, with improved sensitivity and specificity to diseased tissue and potential for use as an estimator of vascular permeability and the enhanced permeability and retention (EPR) effect in tumors.

Published
2024
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31. Factor XII and uPAR upregulate neutrophil functions to influence wound healing

Author

Stavrou, Evi X., Fang, Chao, Bane, Kara L., Long, Andy T., Naudin, Clement, Kucukal, Erdem, Gandhi, Agharnan, Brett-Morris, Adina, Mumaw, Michele M., Izadmehr, Sudeh, Merkulova, Alona, Reynolds, Cindy C., Alhalabi, Omar, Nayak, Lalitha, Yu, Wen-Mei, Qu, Cheng-Kui, Meyerson, Howard J., Dubyak, George R., Gurkan, Umut A., Nieman, Marvin T., Gupta, Anirban Sen, Renne, Thomas, and Schmaier, Alvin H.

Subjects
Cell receptors -- Health aspects, Blood coagulation factors -- Health aspects, Wound healing -- Analysis -- Genetic aspects, Neutrophils -- Genetic aspects -- Health aspects, Health care industry
Abstract

Coagulation factor XII (FXII) deficiency Is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice ([F12.sup.-/-]) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor-mediated (uPAR-mediated) Akt2 phosphorylation at [S.sup.474] ([pAktS.sup.474]). Downstream of [pAkt2S.sup.474], FXII stimulation of neutrophils upregulated surface expression of [[alpha].sub.M][[beta].sub.2] integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in [F12.sup.-/-] mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into [F12.sup.-/-] hosts was sufficient to correct the neutrophil migration defect in [F12.sup.-/-] mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated., Introduction Factor XII (FXII) is the zymogen of serine protease factor XIIa (FXIIa). Discovered by Ratnoff 60 years ago, FXII was first recognized as essential for surface-activated blood coagulation. FXII [...]

Published
2018
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32. Sickle red blood cell‐derived extracellular vesicles activate endothelial cells and enhance sickle red cell adhesion mediated by von Willebrand factor

Author

An, Ran, primary, Man, Yuncheng, additional, Cheng, Kevin, additional, Zhang, Tianyi, additional, Chen, Chunsheng, additional, Wang, Fang, additional, Abdulla, Fuad, additional, Kucukal, Erdem, additional, Wulftange, William J., additional, Goreke, Utku, additional, Bode, Allison, additional, Nayak, Lalitha V., additional, Vercellotti, Gregory M., additional, Belcher, John D., additional, Little, Jane A., additional, and Gurkan, Umut A., additional

Published
2023
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33. Microfluidic concurrent assessment of red blood cell adhesion and microcapillary occlusion: potential hemorheological biomarkers in sickle cell disease

Author

Man, Yuncheng, primary, Wu, Douglas H., additional, An, Ran, additional, Wei, Peiran, additional, Monchamp, Karamoja, additional, Goreke, Utku, additional, Sekyonda, Zoe, additional, Wulftange, William J., additional, Federici, Chiara, additional, Bode, Allison, additional, Nayak, Lalitha V., additional, Little, Jane A., additional, and Gurkan, Umut A., additional

Published
2023
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37. Real-time imaging of nanobubble ultrasound contrast agent flow, extravasation, and diffusion through an extracellular matrix using a microfluidic model.

Author

Cooley, Michaela B., Wulftange, William J., Wegierak, Dana, Goreke, Utku, Abenojar, Eric C., Gurkan, Umut A., and Exner, Agata A.

Subjects
MICROBUBBLE diagnosis, ULTRASOUND contrast media, MICROBUBBLES, EXTRACELLULAR matrix, ULTRASONIC imaging, EXTRAVASATION, MICROFLUIDIC devices
Abstract

Lipid shell-stabilized nanoparticles with a perfluorocarbon gas-core, or nanobubbles, have recently attracted attention as a new contrast agent for molecular ultrasound imaging and image-guided therapy. Due to their small size (∼275 nm diameter) and flexible shell, nanobubbles have been shown to extravasate through hyperpermeable vasculature (e.g., in tumors). However, little is known about the dynamics and depth of extravasation of intact, acoustically active nanobubbles. Accordingly, in this work, we developed a microfluidic chip with a lumen and extracellular matrix (ECM) and imaging method that allows real-time imaging and characterization of the extravasation process with high-frequency ultrasound. The microfluidic device has a lumen and is surrounded by an extracellular matrix with tunable porosity. The combination of ultrasound imaging and the microfluidic chip advantageously produces real-time images of the entire length and depth of the matrix. This captures the matrix heterogeneity, offering advantages over other imaging techniques with smaller fields of view. Results from this study show that nanobubbles diffuse through a 1.3 μm pore size (2 mg mL−1) collagen I matrix 25× faster with a penetration depth that was 0.19 mm deeper than a 3.7 μm (4 mg mL−1) matrix. In the 3.7 μm pore size matrix, nanobubbles diffused 92× faster than large nanobubbles (∼875 nm diameter). Decorrelation time analysis was successfully used to differentiate flowing and extra-luminally diffusing nanobubbles. In this work, we show for the first time that combination of an ultrasound-capable microfluidic chip and real-time imaging provided valuable insight into spatiotemporal nanoparticle movement through a heterogeneous extracellular matrix. This work could help accurately predict parameters (e.g., injection dosage) that improve translation of nanoparticles from in vitro to in vivo environments. [ABSTRACT FROM AUTHOR]

Published
2023
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39. PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin

Author

Elagooz, Reem, primary, Dhara, Anita R., additional, Gott, Rose M., additional, Adams, Sarah E., additional, White, Rachael A., additional, Ghosh, Arnab, additional, Ganguly, Shinjini, additional, Man, Yuncheng, additional, Owusu-Ansah, Amma, additional, Mian, Omar Y., additional, Gurkan, Umut A., additional, Komar, Anton A., additional, Ramamoorthy, Mahesh, additional, and Gnanapragasam, Merlin Nithya, additional

Published
2022
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46. Extracellular Vesicles from Sickle Red Blood Cells Activate Endothelial Cells and Trigger Von Willebrand Factor-Mediated Sickle Red Cell Adhesion

Author

An, Ran, primary, Man, Yuncheng, additional, Cheng, Kevin, additional, Zhang, Tianyi, additional, Chen, Chunsheng, additional, Kucukal, Erdem, additional, Wulftange, William, additional, Goreke, Utku, additional, Bode, Allison, additional, Nayak, Lalitha, additional, Vercellotti, Gregory M., additional, Belcher, John D, additional, Little, Jane Alison, additional, and Gurkan, Umut A., additional

Published
2022
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49. OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability

Author

Man, Yuncheng, primary, An, Ran, additional, Monchamp, Karamoja, additional, Sekyonda, Zoe, additional, Kucukal, Erdem, additional, Federici, Chiara, additional, Wulftange, William J., additional, Goreke, Utku, additional, Bode, Allison, additional, Sheehan, Vivien A., additional, and Gurkan, Umut A., additional

Published
2022
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50. Platelet-Inspired Intravenous Nanomedicine for Injury-Targeted Direct Delivery of Thrombin to Augment Hemostasis in Coagulopathies

Author

Girish, Aditya, primary, Jolly, Ketan, additional, Alsaadi, Nijmeh, additional, de la Fuente, Maria, additional, Recchione, Arielle, additional, An, Ran, additional, Disharoon, Dante, additional, Secunda, Zachary, additional, Raghunathan, Shruti, additional, Luc, Norman F, additional, Desai, Cian, additional, Knauss, Elizabeth, additional, Han, Xu, additional, Hu, Keren, additional, Wang, Hanyang, additional, Sekhon, Ujjal Didar Singh, additional, Rohner, Nathan, additional, Gurkan, Umut A, additional, Nieman, Marvin, additional, Neal, Matthew D., additional, and Sen Gupta, Anirban, additional

Published
2022
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