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1. Unique molecular signatures sustained in circulating monocytes and regulatory T cells in convalescent COVID-19 patients

Author

Hoffmann, Andrew D., Weinberg, Sam E., Swaminathan, Suchitra, Chaudhuri, Shuvam, Almubarak, Hannah Faisal, Schipma, Matthew J., Mao, Chengsheng, Wang, Xinkun, El-Shennawy, Lamiaa, Dashzeveg, Nurmaa K., Wei, Juncheng, Mehl, Paul J., Shihadah, Laura J., Wai, Ching Man, Ostiguin, Carolina, Jia, Yuzhi, D'Amico, Paolo, Wang, Neale R., Luo, Yuan, Demonbreun, Alexis R., Ison, Michael G., Liu, Huiping, and Fang, Deyu

Published
2023
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2. Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2

Author

El-Shennawy, Lamiaa, Hoffmann, Andrew D., Dashzeveg, Nurmaa Khund, McAndrews, Kathleen M., Mehl, Paul J., Cornish, Daphne, Yu, Zihao, Tokars, Valerie L., Nicolaescu, Vlad, Tomatsidou, Anastasia, Mao, Chengsheng, Felicelli, Christopher J., Tsai, Chia-Feng, Ostiguin, Carolina, Jia, Yuzhi, Li, Lin, Furlong, Kevin, Wysocki, Jan, Luo, Xin, Ruivo, Carolina F., Batlle, Daniel, Hope, Thomas J., Shen, Yang, Chae, Young Kwang, Zhang, Hui, LeBleu, Valerie S., Shi, Tujin, Swaminathan, Suchitra, Luo, Yuan, Missiakas, Dominique, Randall, Glenn C., Demonbreun, Alexis R., Ison, Michael G., Kalluri, Raghu, Fang, Deyu, and Liu, Huiping

Published
2022
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3. Physics-driven structural docking and protein language models accelerate antibody screening and design for broad-spectrum antiviral therapy

Author

Almubarak, Hannah Faisal, primary, Tan, Wuwei, additional, Hoffmann, Andrew D., additional, Wei, Juncheng, additional, El-Shennawy, Lamiaa, additional, Squires, Joshua R., additional, Sun, Yuanfei, additional, Dashzeveg, Nurmaa K., additional, Simonton, Brooke, additional, Jia, Yuzhi, additional, Iyer, Radhika, additional, Xu, Yanan, additional, Nicolaescu, Vlad, additional, Elli, Derek, additional, Randall, Glenn C., additional, Schipma, Matthew J., additional, Swaminathan, Suchitra, additional, Ison, Michael G., additional, Liu, Huiping, additional, Fang, Deyu, additional, and Shen, Yang, additional

Published
2024
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4. Hedgehog–FGF signaling axis patterns anterior mesoderm during gastrulation

Author

Guzzetta, Alexander, Koska, Mervenaz, Rowton, Megan, Sullivan, Kaelan R., Jacobs-Li, Jessica, Kweon, Junghun, Hidalgo, Hunter, Eckart, Heather, Hoffmann, Andrew D., Back, Rebecca, Lozano, Stephanie, Moon, Anne M., Basu, Anindita, Bressan, Michael, Pott, Sebastian, and Moskowitz, Ivan P.

Published
2020

5. ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer

Author

Taftaf, Rokana, Liu, Xia, Singh, Salendra, Jia, Yuzhi, Dashzeveg, Nurmaa K., Hoffmann, Andrew D., El-Shennawy, Lamiaa, Ramos, Erika K., Adorno-Cruz, Valery, Schuster, Emma J., Scholten, David, Patel, Dhwani, Zhang, Youbin, Davis, Andrew A., Reduzzi, Carolina, Cao, Yue, D’Amico, Paolo, Shen, Yang, Cristofanilli, Massimo, Muller, William A., Varadan, Vinay, and Liu, Huiping

Published
2021
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6. Supplementary Video S20 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, primary, Zhang, Youbin, primary, Gerratana, Lorenzo, primary, Patel, Priyam, primary, Shajahan, Asif, primary, Dandar, Tsogbadrakh, primary, Ramos, Erika K., primary, Almubarak, Hannah F., primary, Adorno-Cruz, Valery, primary, Taftaf, Rokana, primary, Schuster, Emma J., primary, Scholten, David, primary, Sokolowski, Michael T., primary, Reduzzi, Carolina, primary, El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., primary, Manai, Maroua, primary, Zhang, Qiang, primary, D'Amico, Paolo, primary, Azadi, Parastoo, primary, Colley, Karen J., primary, Platanias, Leonidas C., primary, Shah, Ami N., primary, Gradishar, William J., primary, Cristofanilli, Massimo, primary, Muller, William A., primary, Cobb, Brian A., primary, and Liu, Huiping, primary

Published
2023
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7. Supplementary Excel S3 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, primary, Zhang, Youbin, primary, Gerratana, Lorenzo, primary, Patel, Priyam, primary, Shajahan, Asif, primary, Dandar, Tsogbadrakh, primary, Ramos, Erika K., primary, Almubarak, Hannah F., primary, Adorno-Cruz, Valery, primary, Taftaf, Rokana, primary, Schuster, Emma J., primary, Scholten, David, primary, Sokolowski, Michael T., primary, Reduzzi, Carolina, primary, El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., primary, Manai, Maroua, primary, Zhang, Qiang, primary, D'Amico, Paolo, primary, Azadi, Parastoo, primary, Colley, Karen J., primary, Platanias, Leonidas C., primary, Shah, Ami N., primary, Gradishar, William J., primary, Cristofanilli, Massimo, primary, Muller, William A., primary, Cobb, Brian A., primary, and Liu, Huiping, primary

Published
2023
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8. Data from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, primary, Zhang, Youbin, primary, Gerratana, Lorenzo, primary, Patel, Priyam, primary, Shajahan, Asif, primary, Dandar, Tsogbadrakh, primary, Ramos, Erika K., primary, Almubarak, Hannah F., primary, Adorno-Cruz, Valery, primary, Taftaf, Rokana, primary, Schuster, Emma J., primary, Scholten, David, primary, Sokolowski, Michael T., primary, Reduzzi, Carolina, primary, El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., primary, Manai, Maroua, primary, Zhang, Qiang, primary, D'Amico, Paolo, primary, Azadi, Parastoo, primary, Colley, Karen J., primary, Platanias, Leonidas C., primary, Shah, Ami N., primary, Gradishar, William J., primary, Cristofanilli, Massimo, primary, Muller, William A., primary, Cobb, Brian A., primary, and Liu, Huiping, primary

Published
2023
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9. Supplementary Tables S1-S2 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, primary, Zhang, Youbin, primary, Gerratana, Lorenzo, primary, Patel, Priyam, primary, Shajahan, Asif, primary, Dandar, Tsogbadrakh, primary, Ramos, Erika K., primary, Almubarak, Hannah F., primary, Adorno-Cruz, Valery, primary, Taftaf, Rokana, primary, Schuster, Emma J., primary, Scholten, David, primary, Sokolowski, Michael T., primary, Reduzzi, Carolina, primary, El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., primary, Manai, Maroua, primary, Zhang, Qiang, primary, D'Amico, Paolo, primary, Azadi, Parastoo, primary, Colley, Karen J., primary, Platanias, Leonidas C., primary, Shah, Ami N., primary, Gradishar, William J., primary, Cristofanilli, Massimo, primary, Muller, William A., primary, Cobb, Brian A., primary, and Liu, Huiping, primary

Published
2023
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10. Supplementary Figures S1-S17 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, primary, Zhang, Youbin, primary, Gerratana, Lorenzo, primary, Patel, Priyam, primary, Shajahan, Asif, primary, Dandar, Tsogbadrakh, primary, Ramos, Erika K., primary, Almubarak, Hannah F., primary, Adorno-Cruz, Valery, primary, Taftaf, Rokana, primary, Schuster, Emma J., primary, Scholten, David, primary, Sokolowski, Michael T., primary, Reduzzi, Carolina, primary, El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., primary, Manai, Maroua, primary, Zhang, Qiang, primary, D'Amico, Paolo, primary, Azadi, Parastoo, primary, Colley, Karen J., primary, Platanias, Leonidas C., primary, Shah, Ami N., primary, Gradishar, William J., primary, Cristofanilli, Massimo, primary, Muller, William A., primary, Cobb, Brian A., primary, and Liu, Huiping, primary

Published
2023
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11. Evolutionarily conserved Tbx5–Wnt2/2b pathway orchestrates cardiopulmonary development

Author

Steimle, Jeffrey D., Rankin, Scott A., Slagle, Christopher E., Bekeny, Jenna, Rydeen, Ariel B., Chan, Sunny Sun-Kin, Kweon, Junghun, Yang, Xinan H., Ikegami, Kohta, Nadadur, Rangarajan D., Rowton, Megan, Hoffmann, Andrew D., Lazarevic, Sonja, Thomas, William, Anderson, Erin A. T. Boyle, Horb, Marko E., Luna-Zurita, Luis, Ho, Robert K., Kyba, Michael, Jensen, Bjarke, Zorn, Aaron M., Conlon, Frank L., and Moskowitz, Ivan P.

Published
2018

12. Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer

Author

Dashzeveg, Nurmaa K., primary, Jia, Yuzhi, additional, Zhang, Youbin, additional, Gerratana, Lorenzo, additional, Patel, Priyam, additional, Shajahan, Asif, additional, Dandar, Tsogbadrakh, additional, Ramos, Erika K., additional, Almubarak, Hannah F., additional, Adorno-Cruz, Valery, additional, Taftaf, Rokana, additional, Schuster, Emma J., additional, Scholten, David, additional, Sokolowski, Michael T., additional, Reduzzi, Carolina, additional, El-Shennawy, Lamiaa, additional, Hoffmann, Andrew D., additional, Manai, Maroua, additional, Zhang, Qiang, additional, D'Amico, Paolo, additional, Azadi, Parastoo, additional, Colley, Karen J., additional, Platanias, Leonidas C., additional, Shah, Ami N., additional, Gradishar, William J., additional, Cristofanilli, Massimo, additional, Muller, William A., additional, Cobb, Brian A., additional, and Liu, Huiping, additional

Published
2023
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15. Machine learning-assisted elucidation of CD81–CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

Author

Ramos, Erika K, primary, Tsai, Chia-Feng, additional, Jia, Yuzhi, additional, Cao, Yue, additional, Manu, Megan, additional, Taftaf, Rokana, additional, Hoffmann, Andrew D, additional, El-Shennawy, Lamiaa, additional, Gritsenko, Marina A, additional, Adorno-Cruz, Valery, additional, Schuster, Emma J, additional, Scholten, David, additional, Patel, Dhwani, additional, Liu, Xia, additional, Patel, Priyam, additional, Wray, Brian, additional, Zhang, Youbin, additional, Zhang, Shanshan, additional, Moore, Ronald J, additional, Mathews, Jeremy V, additional, Schipma, Matthew J, additional, Liu, Tao, additional, Tokars, Valerie L, additional, Cristofanilli, Massimo, additional, Shi, Tujin, additional, Shen, Yang, additional, Dashzeveg, Nurmaa K, additional, and Liu, Huiping, additional

Published
2022
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16. Hedgehog signaling activates a mammalian heterochronic gene regulatory network controlling differentiation timing across lineages

Author

Rowton, Megan, primary, Perez-Cervantes, Carlos, additional, Hur, Suzy, additional, Jacobs-Li, Jessica, additional, Lu, Emery, additional, Deng, Nikita, additional, Guzzetta, Alexander, additional, Hoffmann, Andrew D., additional, Stocker, Matthew, additional, Steimle, Jeffrey D., additional, Lazarevic, Sonja, additional, Oubaha, Sophie, additional, Yang, Xinan H., additional, Kim, Chul, additional, Yu, Shuhan, additional, Eckart, Heather, additional, Koska, Mervenaz, additional, Hanson, Erika, additional, Chan, Sunny S.K., additional, Garry, Daniel J., additional, Kyba, Michael, additional, Basu, Anindita, additional, Ikegami, Kohta, additional, Pott, Sebastian, additional, and Moskowitz, Ivan P., additional

Published
2022
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18. Author response: Machine learning-assisted elucidation of CD81–CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

Author

Ramos, Erika K, primary, Tsai, Chia-Feng, additional, Jia, Yuzhi, additional, Cao, Yue, additional, Manu, Megan, additional, Taftaf, Rokana, additional, Hoffmann, Andrew D, additional, El-Shennawy, Lamiaa, additional, Gritsenko, Marina A, additional, Adorno-Cruz, Valery, additional, Schuster, Emma J, additional, Scholten, David, additional, Patel, Dhwani, additional, Liu, Xia, additional, Patel, Priyam, additional, Wray, Brian, additional, Zhang, Youbin, additional, Zhang, Shanshan, additional, Moore, Ronald J, additional, Mathews, Jeremy V, additional, Schipma, Matthew J, additional, Liu, Tao, additional, Tokars, Valerie L, additional, Cristofanilli, Massimo, additional, Shi, Tujin, additional, Shen, Yang, additional, Dashzeveg, Nurmaa K, additional, and Liu, Huiping, additional

Published
2022
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19. Author Reply to Peer Reviews of Machine learning-assisted elucidation of CD81-CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

Author

Ramos, Erika K, primary, Tsai, Chia-Feng, additional, Jia, Yuzhi, additional, Cao, Yue, additional, Manu, Megan, additional, Taftaf, Rokana, additional, Hoffmann, Andrew D, additional, El-Shennawy, Lamiaa, additional, Gritsenko, Marina, additional, Adorno-Cruz, Valery, additional, Schuster, Emma J, additional, Scholten, David, additional, Patel, Dhwani, additional, Liu, Xia, additional, Patel, Priyam, additional, Wray, Brian, additional, Zhang, Youbin, additional, Zhang, Shanshan, additional, Moore, Ronald, additional, Mathews, Jeremy V, additional, Schipma, Matthew, additional, Liu, Tao, additional, Tokars, Valerie L., additional, Cristofanilli, Massimo, additional, Shi, Tujin, additional, Shen, Yang, additional, Dashzeveg, Nurmaa K., additional, and Liu, Huiping, additional

Published
2022
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20. Unique molecular signatures sustained in circulating monocytes and regulatory T cells in Convalescent COVID-19 patients

Author

Hoffmann, Andrew D., primary, Weinberg, Sam E., additional, Swaminathan, Suchitra, additional, Chaudhuri, Shuvam, additional, Mubarak, Hannah Faisal, additional, Schipma, Matthew J., additional, Mao, Chengsheng, additional, Wang, Xinkun, additional, El-Shennawy, Lamiaa, additional, Dashzeveg, Nurmaa K., additional, Wei, Juncheng, additional, Mehl, Paul J., additional, Shihadah, Laura J., additional, Wai, Ching Man, additional, Ostiguin, Carolina, additional, Jia, Yuzhi, additional, D’Amico, Paolo, additional, Wang, Neale R., additional, Luo, Yuan, additional, Demonbreun, Alexis R., additional, Ison, Michael G., additional, Liu, Huiping, additional, and Fang, Deyu, additional

Published
2022
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21. CD81 partners with CD44 in promoting exosome biogenesis, tumor cluster formation, and lung metastasis in triple negative breast cancer

Author

Ramos, Erika K, primary, Tsai, Chia-Feng, additional, Dashzeveg, Nurmaa K., additional, Jia, Yuzhi, additional, Cao, Yue, additional, Manu, Megan, additional, Taftaf, Rokana, additional, Hoffmann, Andrew D, additional, El-Shennawy, Lamiaa, additional, Gritsenko, Marina A., additional, Adorno-Cruz, Valery, additional, Schuster, Emma J, additional, Scholten, David, additional, Patel, Dhwani, additional, Liu, Xia, additional, Patel, Priyam, additional, Wray, Brian, additional, Zhang, Youbin, additional, Zhang, Shanshan, additional, Moore, Ronald J, additional, Schipma, Matthew J, additional, Liu, Tao, additional, Tokars, Valerie L., additional, Cristofanilli, Massimo, additional, Shi, Tujin, additional, Shen, Yang, additional, and Liu, Huiping, additional

Published
2022
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23. ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment

Author

Steimle, Jeffrey D., primary, Kim, Chul, additional, Nadadur, Rangarajan D., additional, Wang, Zhezhen, additional, Hoffmann, Andrew D., additional, Hanson, Erika, additional, Kweon, Junghun, additional, Sinha, Tanvi, additional, Choi, Kyunghee, additional, Black, Brian L., additional, Cunningham, John M., additional, Ikegami, Kohta, additional, and Moskowitz, Ivan P., additional

Published
2021
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24. Circulating ACE2-expressing Exosomes Block SARS-CoV-2 Infection as an Innate Antiviral Mechanism

Author

El-Shennawy, Lamiaa, primary, Hoffmann, Andrew D., additional, Dashzeveg, Nurmaa K., additional, Mehl, Paul J., additional, Yu, Zihao, additional, Tokars, Valerie L., additional, Nicolaescu, Vlad, additional, Ostiguin, Carolina, additional, Jia, Yuzhi, additional, Li, Lin, additional, Furlong, Kevin, additional, Mao, Chengsheng, additional, Wysocki, Jan, additional, Batlle, Daniel, additional, Hope, Thomas J., additional, Shen, Yang, additional, Luo, Yuan, additional, Chae, Young, additional, Zhang, Hui, additional, Swaminathan, Suchitra, additional, Randall, Glenn C., additional, Demonbreun, Alexis R, additional, Ison, Michael G, additional, Fang, Deyu, additional, and Liu, Huiping, additional

Published
2020
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26. Hedgehog signaling controls progenitor differentiation timing

Author

Rowton, Megan, Hoffmann, Andrew D., Steimle, Jeffrey D., Hur, Suzy, Yang, Xinan Holly, Guzzetta, Alexander, Lazarevic, Sonja, Kim, Chul, Deng, Nikita, Lu, Emery, Jacobs-Li, Jessica, Yu, Shuhan, Koska, Mervenaz, Hanson, Erika, Perez-Cervantes, Carlos, Chan, Sunny Sun-Kin, Ikegami, Kohta, Garry, Daniel J., Kyba, Michael, and Moskowitz, Ivan P.

Abstract

Hedgehog (Hh) signaling acts as a developmental morphogen that contributes to the diversification of cell fates and tissue patterning in multiple embryonic contexts, as well as regulating the proliferation of adult tissue stem cells1-9. Here, we report a novel function of Hh signaling GLI transcription factors (TFs) in directly governing the timing of cellular differentiation, independent of a role in specification or proliferation. Disruption of active Hh signaling in the embryo resulted in reduced expression of a progenitor-specific transcription factor network and the inappropriate activation of cardiac differentiation-specific gene expression programs. Expression of the activating Hh transcription factor, GLI1, a marker and effector of active Hh signaling, is correlated with stem and progenitor states during the differentiation of all three germ layers in mouse and human. Transient induction of GLI1 in mouse embryonic stem cell (mESC)-derived cardiac and neural progenitors delayed the onset of the cardiomyocyte and neuron differentiation programs, respectively, while activating progenitor-specific gene expression. GLI1 expression in cardiac progenitors promoted a shift in chromatin accessibility towards a progenitor-like profile at distal regulatory elements near Hh-dependent genes. Manipulating the balance of active to repressive GLI TF predominance unveiled a molecular switch that determined the activity patterns of progenitor-specific distal cis-regulatory elements in vitro and in vivo. Overriding this switch through forced expression of a repressive GLI TF in cardiac progenitors in vivo caused precocious cardiomyocyte differentiation and Congenital Heart Disease (CHD). Our data suggest that a GLI TF switch at distal regulatory elements maintains progenitor cell status and inhibits premature differentiation through the activation and maintenance of a progenitor-specific regulatory network, thus controlling progenitor differentiation timing. We propose a novel molecular paradigm for progenitor maintenance in diverse cellular contexts by signal-dependent TFs with implications for organ development, regenerative potential, and Hh-driven cancers.

Published
2018
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30. Correction: Foxf Genes Integrate Tbx5 and Hedgehog Pathways in the Second Heart Field for Cardiac Septation

Author

Hoffmann, Andrew D., primary, Yang, Xinan Holly, additional, Burnicka-Turek, Ozanna, additional, Bosman, Joshua D., additional, Ren, Xiaomeng, additional, Xie, Linglin, additional, Steimle, Jeffrey D., additional, Vokes, Steven A., additional, McMahon, Andrew P., additional, Kalinichenko, Vladimir V., additional, and Moskowitz, Ivan P., additional

Published
2016
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35. Novel antibody language model accelerates IgG screening and design for broad-spectrum antiviral therapy.

Author

Almubarak HF, Tan W, Hoffmann AD, Sun Y, Wei J, El-Shennawy L, Squires JR, Dashzeveg NK, Simonton B, Jia Y, Iyer R, Xu Y, Nicolaescu V, Elli D, Randall GC, Schipma MJ, Swaminathan S, Ison MG, Liu H, Fang D, and Shen Y

Abstract

Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline AbGen that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. Our AbGen centers around a novel antibody language model (AbLM) that is pretrained on 12 million generic protein domain sequences and fine-tuned on 4,000+ paired VH-VL sequences, with IgG-specific CDR-masking and VH-VL cross-attention. AbLM provides a latent space of IgG sequence embeddings for AbGen, including (a) landscapes of IgGs' activities in neutralizing the wild-type virus are analyzed through structure prediction for IgG and IgG-antigen (viral protein spike's receptor binding domain, RBD) interactions; and (b) landscapes of IgGs' susceptibility in neutralizing variant viruses are predicted through Gaussian process regression, despite that as few as 14 clinical antibodies' responses to variants of concern are available. The AbGen pipeline was applied to over 1300 IgG sequences we collected from RBD-binding B cells of convalescent patients. With experimental validations, AbGen efficiently prioritized IgG candidates against a broad spectrum of viral variants (wildtype, Delta, and Omicron), preventing the infection of host cells in vitro and hACE2 transgenic mice in vivo . Compared to other existing protein language models that require 10-100 times more model parameters, AbLM improved the precision from around 50% to 75% to predict IgGs with low variant susceptibility. Furthermore, AbGen enables structure-based computational protein redesign for selected IgG clones with single amino acid substitutions at the RBD-binding interface that doubled the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screen and re-design combining data-driven protein language models and Kriging for antibody sequence analysis and activity prediction, in synergy with physics-driven protein docking and design for antibody-antigen interface analyses and functional optimization., Competing Interests: Competing interest statement Northwestern University and H. L., D. F., L. E., A. D. H., and N. K. D. hold issued and/or provisional patents in IgG and exosome therapeutics. H.L., D. F., and A.D.H are scientific co-founders of ExoMira Medicine Inc.

Published
2024
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36. Unique molecular signatures sustained in circulating monocytes and regulatory T cells in Convalescent COVID-19 patients.

Author

Hoffmann AD, Weinberg SE, Swaminathan S, Chaudhuri S, Mubarak HF, Schipma MJ, Mao C, Wang X, El-Shennawy L, Dashzeveg NK, Wei J, Mehl PJ, Shihadah LJ, Wai CM, Ostiguin C, Jia Y, D'Amico P, Wang NR, Luo Y, Demonbreun AR, Ison MG, Liu H, and Fang D

Abstract

Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized multi-omic single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including covenlesent COVID-19 and sero-negative controls. The reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells are significantly associated with the patients recovered from severe COVID-19. Consistently, sc-RNA seq analysis reveals seven heterogeneous clusters of monocytes (M0-M6) and ten Treg clusters (T0-T9) featuring distinct molecular signatures and associated with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocyte and Treg expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters with S100 family genes: S100A8 & A9 with high HLA-I whereas S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, and a unique TGF-β high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-ived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

Published
2022
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37. ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis.

Author

Adorno-Cruz V, Hoffmann AD, Liu X, Dashzeveg NK, Taftaf R, Wray B, Keri RA, and Liu H

Abstract

Cancer metastasis is largely incurable and accounts for 90% of breast cancer deaths, especially for the aggressive basal-like or triple negative breast cancer (TNBC). Combining patient database analyses and functional studies, we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis, such as miR-206 that inhibits stemness and metastasis of TNBC. Here we report that the integrin receptor CD49b-encoding ITGA2 , a direct target of miR-206, promotes breast cancer stemness and metastasis. ITGA2 knockdown suppressed self-renewal related mammosphere formation and pluripotency marker expression, inhibited cell cycling, compromised migration and invasion, and therefore decreased lung metastasis of breast cancer. ITGA2 overexpression reversed miR-206-caused cell cycle arrest in G1. RNA sequencing analyses revealed that ITGA2 knockdown inhibits genes related to cell cycle regulation and lipid metabolism, including CCND1 and ACLY as representative targets, respectively. Knockdown of CCND1 or ACLY inhibits mammosphere formation of breast cancer cells. Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest. ACLY -encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA levels. CCND1 knockdown further mimics ITGA2 knockdown in abolishing lung colonization of breast cancer cells. We identified that the low levels of miR-206 as well as high expression levels of ITGA2 , ACLY and CCND1 are associated with an unfavorable relapse-free survival of the patients with estrogen receptor-negative or high grade breast cancer, especially basal-like or TNBC, possibly serving as potential biomarkers of cancer stemness and therapeutic targets of breast cancer metastasis., (© 2020 The Authors.)

Published
2020
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