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1. Dynamic lipidome alterations associated with human health, disease and ageing.

Author

Hornburg, Daniel, Wu, Si, Moqri, Mahdi, Zhou, Xin, Contrepois, Kevin, Bararpour, Nasim, Su, Baolong, Metwally, Ahmed, Avina, Monica, Zhou, Wenyu, Ubellacker, Jessalyn, Mishra, Tejaswini, Schüssler-Fiorenza Rose, Sophia, Kavathas, Paula, Williams, Kevin, Snyder, Michael, and Traber, Gavin

Subjects
Humans, Insulin Resistance, Lipidomics, Aging, Ceramides, Inflammation
Abstract

Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management and cellular signalling. Here, we report >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation, as well as cytokine-lipidome networks. We performed comprehensive longitudinal lipidomic profiling and analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average 3.2 years) to define the distinct physiological roles of complex lipid subclasses, including large and small triacylglycerols, ester- and ether-linked phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, cholesterol esters and ceramides. Our findings reveal dynamic changes in the plasma lipidome during respiratory viral infection, insulin resistance and ageing, suggesting that lipids may have roles in immune homoeostasis and inflammation regulation. Individuals with insulin resistance exhibit disturbed immune homoeostasis, altered associations between lipids and clinical markers, and accelerated changes in specific lipid subclasses during ageing. Our dataset based on longitudinal deep lipidome profiling offers insights into personalized ageing, metabolic health and inflammation, potentially guiding future monitoring and intervention strategies.

Published
2023

3. Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

Author

Zhou, Xin, Shen, Xiaotao, Johnson, Jethro S., Spakowicz, Daniel J., Agnello, Melissa, Zhou, Wenyu, Avina, Monica, Honkala, Alexander, Chleilat, Faye, Chen, Shirley Jingyi, Cha, Kexin, Leopold, Shana, Zhu, Chenchen, Chen, Lei, Lyu, Lin, Hornburg, Daniel, Wu, Si, Zhang, Xinyue, Jiang, Chao, Jiang, Liuyiqi, Jiang, Lihua, Jian, Ruiqi, Brooks, Andrew W., Wang, Meng, Contrepois, Kévin, Gao, Peng, Rose, Sophia Miryam Schüssler-Fiorenza, Tran, Thi Dong Binh, Nguyen, Hoan, Celli, Alessandra, Hong, Bo-Young, Bautista, Eddy J., Dorsett, Yair, Kavathas, Paula B., Zhou, Yanjiao, Sodergren, Erica, Weinstock, George M., and Snyder, Michael P.

Published
2024
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7. Early prediction and longitudinal modeling of preeclampsia from multiomics

Author

Marić, Ivana, Contrepois, Kévin, Moufarrej, Mira N., Stelzer, Ina A., Feyaerts, Dorien, Han, Xiaoyuan, Tang, Andy, Stanley, Natalie, Wong, Ronald J., Traber, Gavin M., Ellenberger, Mathew, Chang, Alan L., Fallahzadeh, Ramin, Nassar, Huda, Becker, Martin, Xenochristou, Maria, Espinosa, Camilo, De Francesco, Davide, Ghaemi, Mohammad S., Costello, Elizabeth K., Culos, Anthony, Ling, Xuefeng B., Sylvester, Karl G., Darmstadt, Gary L., Winn, Virginia D., Shaw, Gary M., Relman, David A., Quake, Stephen R., Angst, Martin S., Snyder, Michael P., Stevenson, David K., Gaudilliere, Brice, and Aghaeepour, Nima

Published
2022
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9. Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

Author

Zhou, Xin, primary, Shen, Xiaotao, additional, Johnson, Jethro, additional, Spakowicz, Daniel, additional, Agnello, Melissa, additional, Zhou, Wenyu, additional, Avina, Monica, additional, Honkala, Alexander, additional, Chleilat, Faye, additional, Chen, Shirley Jingyi, additional, Cha, Kexin, additional, Leopold, Shana, additional, Zhu, Chenchen, additional, Chen, Lei, additional, Lyu, Lin, additional, Hornburg, Daniel, additional, Wu, Si, additional, Zhang, Xinyue, additional, Jiang, Chao, additional, Jiang, Liuyiqi, additional, jiang, lihua, additional, Jian, Ruiqi, additional, Brooks, Andrew W, additional, Wang, Meng, additional, Contrepois, Kevin, additional, Gao, Peng, additional, Schussler-Fiorenza Rose, Sophia Miryam, additional, Tran, Thi Dong Binh, additional, Nguyen, Hoan, additional, Celli, Alessandra, additional, Hong, Bo-Young, additional, Bautista, Eddy J, additional, Dorsett, Yair, additional, Kavathas, Paula, additional, zhou, yanjiao, additional, Sodergren, Erica, additional, Weinstock, George M, additional, and Snyder, Michael P, additional

Published
2024
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10. Temporal changes in soluble angiotensin-converting enzyme 2 associated with metabolic health, body composition, and proteome dynamics during a weight loss diet intervention: a randomized trial with implications for the COVID-19 pandemic

Author

Cauwenberghs, Nicholas, Prunicki, Mary, Sabovčik, František, Perelman, Dalia, Contrepois, Kévin, Li, Xiao, Snyder, Michael P, Nadeau, Kari C, Kuznetsova, Tatiana, Haddad, Francois, and Gardner, Christopher D

Published
2021
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12. Towards personalized medicine in maternal and child health: integrating biologic and social determinants

Author

Stevenson, David K., Wong, Ronald J., Aghaeepour, Nima, Maric, Ivana, Angst, Martin S., Contrepois, Kevin, Darmstadt, Gary L., Druzin, Maurice L., Eisenberg, Michael L., Gaudilliere, Brice, Gibbs, Ronald S., Gotlib, Ian H., Gould, Jeffrey B., Lee, Henry C., Ling, Xuefeng B., Mayo, Jonathan A., Moufarrej, Mira N., Quaintance, Cecele C., Quake, Stephen R., Relman, David A., Sirota, Marina, Snyder, Michael P., Sylvester, Karl G., Hao, Shiying, Wise, Paul H., Shaw, Gary M., and Katz, Michael

Published
2021
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13. Multiomic immune clockworks of pregnancy

Author

Peterson, Laura S., Stelzer, Ina A., Tsai, Amy S., Ghaemi, Mohammad S., Han, Xiaoyuan, Ando, Kazuo, Winn, Virginia D., Martinez, Nadine R., Contrepois, Kevin, Moufarrej, Mira N., Quake, Stephen, Relman, David A., Snyder, Michael P., Shaw, Gary M., Stevenson, David K., Wong, Ronald J., Arck, Petra, Angst, Martin S., Aghaeepour, Nima, and Gaudilliere, Brice

Published
2020
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14. Impact of acute lymphoblastic leukemia induction therapy: findings from metabolomics on non-fasted plasma samples from a biorepository

Author

Saito, Toshie, Wei, Yue, Wen, Li, Srinivasan, Chaitanya, Wolthers, Benjamin O., Tsai, Cheng-Yu, Harris, Marian H., Stevenson, Kristen, Byersdorfer, Craig, Oparaji, Judy-April, Fernandez, Christian, Mukherjee, Amitava, Abu-El-Haija, Maisam, Agnihotri, Sameer, Schmiegelow, Kjeld, Showalter, Megan R., Fogle, Paul W., McCulloch, Scott, Contrepois, Kevin, Silverman, Lewis B., Ding, Ying, and Husain, Sohail Z.

Published
2021
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18. Table S2

Author

Alipanah-Lechner, Narges, Neyton, Lucile, Mick, Eran, Willmore, Andrew, Leligdowicz, Aleksandra, Contrepois, Kevin, Jauregui, Alejandra, Zhuo, Hanjing, Hendrickson, Carolyn, Gomez, Antonio, Sinha, Pratik, Kangelaris, Kirsten N., Liu, Kathleen D., A Matthay, Michael, and S. Calfee, Carolyn

Abstract

Metabolites differentially abundant in the hyperinflammatory ARDS phenotype compared to the hypoinflammatory phenotype. Metabolites listed in the order of increasing log2 fold change. Analyses adjusted for age, sex, propofol, dexmedetomidine, and liver and kidney disease.

Published
2022
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20. Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts – implications for clinical biomarker studies.

Author

Ghaemi, Mohammad S., Tarca, Adi L., Romero, Roberto, Stanley, Natalie, Fallahzadeh, Ramin, Tanada, Athena, Culos, Anthony, Ando, Kazuo, Han, Xiaoyuan, Blumenfeld, Yair J., Druzin, Maurice L., El-Sayed, Yasser Y., Gibbs, Ronald S., Winn, Virginia D., Contrepois, Kevin, Ling, Xuefeng B., Wong, Ronald J., Shaw, Gary M., Stevenson, David K., and Gaudilliere, Brice

Subjects
PROTEOMICS, PREECLAMPSIA, PREGNANCY outcomes, PRENATAL care, BLOOD proteins
Abstract

Background: Early identification of pregnant women at risk for preeclampsia (PE) is important, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analyses of plasma proteins feature prominently among molecular approaches used for risk prediction. However, derivation of protein signatures of sufficient predictive power has been challenging. The recent availability of platforms simultaneously assessing over 1000 plasma proteins offers broad examinations of the plasma proteome, which may enable the extraction of proteomic signatures with improved prognostic performance in prenatal care. Objective: The primary aim of this study was to examine the generalizability of proteomic signatures predictive of PE in two cohorts of pregnant women whose plasma proteome was interrogated with the same highly multiplexed platform. Establishing generalizability, or lack thereof, is critical to devise strategies facilitating the development of clinically useful predictive tests. A second aim was to examine the generalizability of protein signatures predictive of gestational age (GA) in uncomplicated pregnancies in the same cohorts to contrast physiological and pathological pregnancy outcomes. Study design: Serial blood samples were collected during the first, second, and third trimesters in 18 women who developed PE and 18 women with uncomplicated pregnancies (Stanford cohort). The second cohort (Detroit), used for comparative analysis, consisted of 76 women with PE and 90 women with uncomplicated pregnancies. Multivariate analyses were applied to infer predictive and cohort-specific proteomic models, which were then tested in the alternate cohort. Gene ontology (GO) analysis was performed to identify biological processes that were over-represented among top-ranked proteins associated with PE. Results: The model derived in the Stanford cohort was highly significant (p = 3.9E–15) and predictive (AUC = 0.96), but failed validation in the Detroit cohort (p = 9.7E–01, AUC = 0.50). Similarly, the model derived in the Detroit cohort was highly significant (p = 1.0E–21, AUC = 0.73), but failed validation in the Stanford cohort (p = 7.3E–02, AUC = 0.60). By contrast, proteomic models predicting GA were readily validated across the Stanford (p = 1.1E–454, R = 0.92) and Detroit cohorts (p = 1.1.E–92, R = 0.92) indicating that the proteomic assay performed well enough to infer a generalizable model across studied cohorts, which makes it less likely that technical aspects of the assay, including batch effects, accounted for observed differences. Conclusions: Results point to a broader issue relevant for proteomic and other omic discovery studies in patient cohorts suffering from a clinical syndrome, such as PE, driven by heterogeneous pathophysiologies. While novel technologies including highly multiplex proteomic arrays and adapted computational algorithms allow for novel discoveries for a particular study cohort, they may not readily generalize across cohorts. A likely reason is that the prevalence of pathophysiologic processes leading up to the “same” clinical syndrome can be distributed differently in different and smaller-sized cohorts. Signatures derived in individual cohorts may simply capture different facets of the spectrum of pathophysiologic processes driving a syndrome. Our findings have important implications for the design of omic studies of a syndrome like PE. They highlight the need for performing such studies in diverse and well-phenotyped patient populations that are large enough to characterize subsets of patients with shared pathophysiologies to then derive subset-specific signatures of sufficient predictive power. [ABSTRACT FROM AUTHOR]

Published
2022
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21. Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts – implications for clinical biomarker studies

Author

Ghaemi, Mohammad S., primary, Tarca, Adi L., additional, Romero, Roberto, additional, Stanley, Natalie, additional, Fallahzadeh, Ramin, additional, Tanada, Athena, additional, Culos, Anthony, additional, Ando, Kazuo, additional, Han, Xiaoyuan, additional, Blumenfeld, Yair J., additional, Druzin, Maurice L., additional, El-Sayed, Yasser Y., additional, Gibbs, Ronald S., additional, Winn, Virginia D., additional, Contrepois, Kevin, additional, Ling, Xuefeng B., additional, Wong, Ronald J., additional, Shaw, Gary M., additional, Stevenson, David K., additional, Gaudilliere, Brice, additional, Aghaeepour, Nima, additional, and Angst, Martin S., additional

Published
2021
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22. Abstract 235: Hypertrophic Cardiomyopathy, a Disease of Altered Cardiac Energetics

Author

Ranjbarvaziri, Sara, primary, Ellenberger, Mathew, additional, Kooiker, Kristi, additional, Fajardo, Giovanni, additional, Zhao, Mingming, additional, Schroer, Alison, additional, Woo, Y Joseph Y, additional, Ruppel, Kathleen M, additional, Spudich, James A, additional, Snyder, Michael, additional, Contrepois, Kevin, additional, and Bernstein, Daniel, additional

Published
2020
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23. Towards personalized medicine in maternal and child health: integrating biologic and social determinants

Author

Stevenson, David K., primary, Wong, Ronald J., additional, Aghaeepour, Nima, additional, Maric, Ivana, additional, Angst, Martin S., additional, Contrepois, Kevin, additional, Darmstadt, Gary L., additional, Druzin, Maurice L., additional, Eisenberg, Michael L., additional, Gaudilliere, Brice, additional, Gibbs, Ronald S., additional, Gotlib, Ian H., additional, Gould, Jeffrey B., additional, Lee, Henry C., additional, Ling, Xuefeng B., additional, Mayo, Jonathan A., additional, Moufarrej, Mira N., additional, Quaintance, Cecele C., additional, Quake, Stephen R., additional, Relman, David A., additional, Sirota, Marina, additional, Snyder, Michael P., additional, Sylvester, Karl G., additional, Hao, Shiying, additional, Wise, Paul H., additional, Shaw, Gary M., additional, and Katz, Michael, additional

Published
2020
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29. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Rozenblatt-Rosen, Orit, primary, Regev, Aviv, additional, Oberdoerffer, Philipp, additional, Nawy, Tal, additional, Hupalowska, Anna, additional, Rood, Jennifer E., additional, Ashenberg, Orr, additional, Cerami, Ethan, additional, Coffey, Robert J., additional, Demir, Emek, additional, Ding, Li, additional, Esplin, Edward D., additional, Ford, James M., additional, Goecks, Jeremy, additional, Ghosh, Sharmistha, additional, Gray, Joe W., additional, Guinney, Justin, additional, Hanlon, Sean E., additional, Hughes, Shannon K., additional, Hwang, E. Shelley, additional, Iacobuzio-Donahue, Christine A., additional, Jané-Valbuena, Judit, additional, Johnson, Bruce E., additional, Lau, Ken S., additional, Lively, Tracy, additional, Mazzilli, Sarah A., additional, Pe’er, Dana, additional, Santagata, Sandro, additional, Shalek, Alex K., additional, Schapiro, Denis, additional, Snyder, Michael P., additional, Sorger, Peter K., additional, Spira, Avrum E., additional, Srivastava, Sudhir, additional, Tan, Kai, additional, West, Robert B., additional, Williams, Elizabeth H., additional, Aberle, Denise, additional, Achilefu, Samuel I., additional, Ademuyiwa, Foluso O., additional, Adey, Andrew C., additional, Aft, Rebecca L., additional, Agarwal, Rachana, additional, Aguilar, Ruben A., additional, Alikarami, Fatemeh, additional, Allaj, Viola, additional, Amos, Christopher, additional, Anders, Robert A., additional, Angelo, Michael R., additional, Anton, Kristen, additional, Aster, Jon C., additional, Babur, Ozgun, additional, Bahmani, Amir, additional, Balsubramani, Akshay, additional, Barrett, David, additional, Beane, Jennifer, additional, Bender, Diane E., additional, Bernt, Kathrin, additional, Berry, Lynne, additional, Betts, Courtney B., additional, Bletz, Julie, additional, Blise, Katie, additional, Boire, Adrienne, additional, Boland, Genevieve, additional, Borowsky, Alexander, additional, Bosse, Kristopher, additional, Bott, Matthew, additional, Boyden, Ed, additional, Brooks, James, additional, Bueno, Raphael, additional, Burlingame, Erik A., additional, Cai, Qiuyin, additional, Campbell, Joshua, additional, Caravan, Wagma, additional, Chaib, Hassan, additional, Chan, Joseph M., additional, Chang, Young Hwan, additional, Chatterjee, Deyali, additional, Chaudhary, Ojasvi, additional, Chen, Alyce A., additional, Chen, Bob, additional, Chen, Changya, additional, Chen, Chia-hui, additional, Chen, Feng, additional, Chen, Yu-An, additional, Chheda, Milan G., additional, Chin, Koei, additional, Chiu, Roxanne, additional, Chu, Shih-Kai, additional, Chuaqui, Rodrigo, additional, Chun, Jaeyoung, additional, Cisneros, Luis, additional, Colditz, Graham A., additional, Cole, Kristina, additional, Collins, Natalie, additional, Contrepois, Kevin, additional, Coussens, Lisa M., additional, Creason, Allison L., additional, Crichton, Daniel, additional, Curtis, Christina, additional, Davidsen, Tanja, additional, Davies, Sherri R., additional, de Bruijn, Ino, additional, Dellostritto, Laura, additional, De Marzo, Angelo, additional, DeNardo, David G., additional, Diep, Dinh, additional, Diskin, Sharon, additional, Doan, Xengie, additional, Drewes, Julia, additional, Dubinett, Stephen, additional, Dyer, Michael, additional, Egger, Jacklynn, additional, Eng, Jennifer, additional, Engelhardt, Barbara, additional, Erwin, Graham, additional, Esserman, Laura, additional, Felmeister, Alex, additional, Feiler, Heidi S., additional, Fields, Ryan C., additional, Fisher, Stephen, additional, Flaherty, Keith, additional, Flournoy, Jennifer, additional, Fortunato, Angelo, additional, Frangieh, Allison, additional, Frye, Jennifer L., additional, Fulton, Robert S., additional, Galipeau, Danielle, additional, Gan, Siting, additional, Gao, Jianjiong, additional, Gao, Long, additional, Gao, Peng, additional, Gao, Vianne R., additional, Geiger, Tim, additional, George, Ajit, additional, Getz, Gad, additional, Giannakis, Marios, additional, Gibbs, David L., additional, Gillanders, William E., additional, Goedegebuure, Simon P., additional, Gould, Alanna, additional, Gowers, Kate, additional, Greenleaf, William, additional, Gresham, Jeremy, additional, Guerriero, Jennifer L., additional, Guha, Tuhin K., additional, Guimaraes, Alexander R., additional, Gutman, David, additional, Hacohen, Nir, additional, Hanlon, Sean, additional, Hansen, Casey R., additional, Harismendy, Olivier, additional, Harris, Kathleen A., additional, Hata, Aaron, additional, Hayashi, Akimasa, additional, Heiser, Cody, additional, Helvie, Karla, additional, Herndon, John M., additional, Hirst, Gilliam, additional, Hodi, Frank, additional, Hollmann, Travis, additional, Horning, Aaron, additional, Hsieh, James J., additional, Hughes, Shannon, additional, Huh, Won Jae, additional, Hunger, Stephen, additional, Hwang, Shelley E., additional, Ijaz, Heba, additional, Izar, Benjamin, additional, Jacobson, Connor A., additional, Janes, Samuel, additional, Jayasinghe, Reyka G., additional, Jiang, Lihua, additional, Johnson, Brett E., additional, Johnson, Bruce, additional, Ju, Tao, additional, Kadara, Humam, additional, Kaestner, Klaus, additional, Kagan, Jacob, additional, Kalinke, Lukas, additional, Keith, Robert, additional, Khan, Aziz, additional, Kibbe, Warren, additional, Kim, Albert H., additional, Kim, Erika, additional, Kim, Junhyong, additional, Kolodzie, Annette, additional, Kopytra, Mateusz, additional, Kotler, Eran, additional, Krueger, Robert, additional, Krysan, Kostyantyn, additional, Kundaje, Anshul, additional, Ladabaum, Uri, additional, Lake, Blue B., additional, Lam, Huy, additional, Laquindanum, Rozelle, additional, Laughney, Ashley M., additional, Lee, Hayan, additional, Lenburg, Marc, additional, Leonard, Carina, additional, Leshchiner, Ignaty, additional, Levy, Rochelle, additional, Li, Jerry, additional, Lian, Christine G., additional, Lim, Kian-Huat, additional, Lin, Jia-Ren, additional, Lin, Yiyun, additional, Liu, Qi, additional, Liu, Ruiyang, additional, Longabaugh, William J.R., additional, Longacre, Teri, additional, Ma, Cynthia X., additional, Macedonia, Mary Catherine, additional, Madison, Tyler, additional, Maher, Christopher A., additional, Maitra, Anirban, additional, Makinen, Netta, additional, Makowski, Danika, additional, Maley, Carlo, additional, Maliga, Zoltan, additional, Mallo, Diego, additional, Maris, John, additional, Markham, Nick, additional, Marks, Jeffrey, additional, Martinez, Daniel, additional, Mashl, Robert J., additional, Masilionais, Ignas, additional, Mason, Jennifer, additional, Massagué, Joan, additional, Massion, Pierre, additional, Mattar, Marissa, additional, Mazurchuk, Richard, additional, Mazutis, Linas, additional, McKinley, Eliot T., additional, McMichael, Joshua F., additional, Merrick, Daniel, additional, Meyerson, Matthew, additional, Miessner, Julia R., additional, Mills, Gordon B., additional, Mills, Meredith, additional, Mondal, Suman B., additional, Mori, Motomi, additional, Mori, Yuriko, additional, Moses, Elizabeth, additional, Mosse, Yael, additional, Muhlich, Jeremy L., additional, Murphy, George F., additional, Navin, Nicholas E., additional, Nederlof, Michel, additional, Ness, Reid, additional, Nevins, Stephanie, additional, Nikolov, Milen, additional, Nirmal, Ajit Johnson, additional, Nolan, Garry, additional, Novikov, Edward, additional, O’Connell, Brendan, additional, Offin, Michael, additional, Oh, Stephen T., additional, Olson, Anastasiya, additional, Ooms, Alex, additional, Ossandon, Miguel, additional, Owzar, Kouros, additional, Parmar, Swapnil, additional, Patel, Tasleema, additional, Patti, Gary J., additional, Pe'er, Itsik, additional, Peng, Tao, additional, Persson, Daniel, additional, Petty, Marvin, additional, Pfister, Hanspeter, additional, Polyak, Kornelia, additional, Pourfarhangi, Kamyar, additional, Puram, Sidharth V., additional, Qiu, Qi, additional, Quintanal-Villalonga, Álvaro, additional, Raj, Arjun, additional, Ramirez-Solano, Marisol, additional, Rashid, Rumana, additional, Reeb, Ashley N., additional, Reid, Mary, additional, Resnick, Adam, additional, Reynolds, Sheila M., additional, Riesterer, Jessica L., additional, Rodig, Scott, additional, Roland, Joseph T., additional, Rosenfield, Sonia, additional, Rotem, Asaf, additional, Roy, Sudipta, additional, Rozenblatt-Rosen, Orit, additional, Rudin, Charles M., additional, Ryser, Marc D., additional, Santi-Vicini, Maria, additional, Sato, Kazuhito, additional, Schrag, Deborah, additional, Schultz, Nikolaus, additional, Sears, Cynthia L., additional, Sears, Rosalie C., additional, Sen, Subrata, additional, Sen, Triparna, additional, Shalek, Alex, additional, Sheng, Jeff, additional, Sheng, Quanhu, additional, Shoghi, Kooresh I., additional, Shrubsole, Martha J., additional, Shyr, Yu, additional, Sibley, Alexander B., additional, Siex, Kiara, additional, Simmons, Alan J., additional, Singer, Dinah S., additional, Sivagnanam, Shamilene, additional, Slyper, Michal, additional, Sokolov, Artem, additional, Song, Sheng-Kwei, additional, Southard-Smith, Austin, additional, Spira, Avrum, additional, Stein, Janet, additional, Storm, Phillip, additional, Stover, Elizabeth, additional, Strand, Siri H., additional, Su, Timothy, additional, Sudar, Damir, additional, Sullivan, Ryan, additional, Surrey, Lea, additional, Suvà, Mario, additional, Terekhanova, Nadezhda V., additional, Ternes, Luke, additional, Thammavong, Lisa, additional, Thibault, Guillaume, additional, Thomas, George V., additional, Thorsson, Vésteinn, additional, Todres, Ellen, additional, Tran, Linh, additional, Tyler, Madison, additional, Uzun, Yasin, additional, Vachani, Anil, additional, Van Allen, Eliezer, additional, Vandekar, Simon, additional, Veis, Deborah J., additional, Vigneau, Sébastien, additional, Vossough, Arastoo, additional, Waanders, Angela, additional, Wagle, Nikhil, additional, Wang, Liang-Bo, additional, Wendl, Michael C., additional, West, Robert, additional, Wu, Chi-yun, additional, Wu, Hao, additional, Wu, Hung-Yi, additional, Wyczalkowski, Matthew A., additional, Xie, Yubin, additional, Yang, Xiaolu, additional, Yapp, Clarence, additional, Yu, Wenbao, additional, Yuan, Yinyin, additional, Zhang, Dadong, additional, Zhang, Kun, additional, Zhang, Mianlei, additional, Zhang, Nancy, additional, Zhang, Yantian, additional, Zhao, Yanyan, additional, Zhou, Daniel Cui, additional, Zhou, Zilu, additional, Zhu, Houxiang, additional, Zhu, Qin, additional, Zhu, Xiangzhu, additional, Zhu, Yuankun, additional, and Zhuang, Xiaowei, additional

Published
2020
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30. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation

Author

Minhas, Paras S., primary, Liu, Ling, additional, Moon, Peter K., additional, Joshi, Amit U., additional, Dove, Christopher, additional, Mhatre, Siddhita, additional, Contrepois, Kevin, additional, Wang, Qian, additional, Lee, Brittany A., additional, Coronado, Michael, additional, Bernstein, Daniel, additional, Snyder, Michael P., additional, Migaud, Marie, additional, Majeti, Ravindra, additional, Mochly-Rosen, Daria, additional, Rabinowitz, Joshua D., additional, and Andreasson, Katrin I., additional

Published
2018
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32. DE NOVO NAD+ SYNTHESIS RESCUES NEUROINFLAMMATION AND ALZHEIMER’S DISEASE PHENOTYPES: MODULATING IMMUNE CELL RESPONSES AND MITOCHONDRIAL BIOENERGETICS

Author

Minhas, Paras Singh, Liu, Ling, Moon, Peter Kim, Mhatre, Siddhita D., Wang, Qian, Coronado, Michael, Contrepois, Kevin, Joshi, Amit U., Dove, Chris G., Kvalheim, Gry, Midttun, Oivind, Majeti, Ravi, Bernstein, Daniel, Mochly-Rosen, Daria, Snyder, Michael, Rabinowitz, Joshua, and Andreasson, Katrin

Published
2018
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33. Macrophage de novo NAD+synthesis specifies immune function in aging and inflammation

Author

Minhas, Paras S., Liu, Ling, Moon, Peter K., Joshi, Amit U., Dove, Christopher, Mhatre, Siddhita, Contrepois, Kevin, Wang, Qian, Lee, Brittany A., Coronado, Michael, Bernstein, Daniel, Snyder, Michael P., Migaud, Marie, Majeti, Ravindra, Mochly-Rosen, Daria, Rabinowitz, Joshua D., and Andreasson, Katrin I.

Abstract

Recent advances highlight a pivotal role for cellular metabolism in programming immune responses. Here, we demonstrate that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) regulates macrophage immune function in aging and inflammation. Isotope tracer studies revealed that macrophage NAD+derives substantially from KP metabolism of tryptophan. Genetic or pharmacological blockade of de novo NAD+synthesis depleted NAD+, suppressed mitochondrial NAD+-dependent signaling and respiration, and impaired phagocytosis and resolution of inflammation. Innate immune challenge triggered upstream KP activation but paradoxically suppressed cell-autonomous NAD+synthesis by limiting the conversion of downstream quinolinate to NAD+, a profile recapitulated in aging macrophages. Increasing de novo NAD+generation in immune-challenged or aged macrophages restored oxidative phosphorylation and homeostatic immune responses. Thus, KP-derived NAD+operates as a metabolic switch to specify macrophage effector responses. Breakdown of de novo NAD+synthesis may underlie declining NAD+levels and rising innate immune dysfunction in aging and age-associated diseases.

Published
2019
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34. O4‐02‐05: DE NOVO NAD+ SYNTHESIS RESCUES NEUROINFLAMMATION AND ALZHEIMER'S DISEASE PHENOTYPES: MODULATING IMMUNE CELL RESPONSES AND MITOCHONDRIAL BIOENERGETICS.

Author

Minhas, Paras Singh, Liu, Ling, Moon, Peter Kim, Mhatre, Siddhita D., Wang, Qian, Coronado, Michael, Contrepois, Kevin, Joshi, Amit U., Dove, Chris G., Kvalheim, Gry, Midttun, Oivind, Majeti, Ravi, Bernstein, Daniel, Mochly-Rosen, Daria, Snyder, Michael, Rabinowitz, Joshua, and Andreasson, Katrin

Published
2018
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35. Abstract 15235: Circulating Immune Profile of Aging, a Translational Study on the Role of Growth Differentiation Factor-15 and Monokine Induced by Interferon gamma

Author

Arthur, Jennifer A, Bouajila, Sara, Amsallem, Myriam, Shen Orr, Shai, Kobayashi, Yukari, Rosenberg-Hasson, Yael, Alpert, Ayelet, Moneghetti, Kegan J, Dekker, Cornelia, Contrepois, Kevin, Martin, Beth A, Kouznetsova, Tatiana, Davis, Mark, Karakikes, Ioannis, Maecker, Holden T, and Haddad, Francois

Abstract

Introduction:While inflammation is frequently found in elderly individuals, it remains controversial whether healthy aging is associated with an increase in pro-inflammatory markers.Objective:To determine the immune profile associated with aging and identify the endothelial effect of these molecules.Methods:The study included a first derivation cohort of 102 healthy individuals (age 20-90 yo, mean age 57.4?18.3 years, 55% of females) free of cardiovascular disease, inflammatory condition or cancer. Targeted immune profiling (48-plex Luminex), C-reactive protein, Growth Differentiation Factor-15 (GDF-15), galactin-3 and metabolic profiling with insulin and comprehensive lipid panel was performed. For validation, we profiled an additional cohort of 78 less healthy individuals and applied an in-vitro endothelial cell validation model investigating the effects of immune molecules on aging stressors.Results:In the derivation cohort, GDF-15 and Monokine induced by Interferon Gamma (MIG also known as CXCL9) were strongly associated with the cardiovascular parameters: pulse wave velocity (PWV) is a marker of arterial stiffness and mitral lateral e? is a marker of myocardial relaxation.. These cytokines were the most correlated with age (R2=0.73 and R2=0.59, for PWV and e?, respectively, p<0.001), a finding which was confirmed in the validation cohort. In-vitro treatment with GDF-15 and CXCL9 attenuated the endothelial dysfunction phenotype (i.e. decrease in eNOS and increase in ICAM-1 mRNA endothelial expression) after exposure to IL-1B and oxidative stress.Conclusions:GDF-15 and CXCL9 are strongly correlated with age and have modulating effects on inflammasome or oxidative stress mediated endothelial cells injury.

Published
2019
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36. 2023 White Paper on Recent Issues in Bioanalysis: Deuterated Drugs; LNP; Tumor/FFPE Biopsy; Targeted Proteomics; Small Molecule Covalent Inhibitors; Chiral Bioanalysis; Remote Regulatory Assessments; Sample Reconciliation/Chain of Custody (PART 1A - Recommendations on Mass Spectrometry, Chromatography, Sample Preparation Latest Developments, Challenges, and Solutions and BMV/Regulated Bioanalysis PART 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/IVD/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

Author

Baratta M, Jian W, Hengel S, Kaur S, Cunliffe J, Boer J, Hughes N, Kar S, Kellie J, Kim YJ, Lassman M, Mehl J, Morgan L, Palandra J, Sarvaiya H, Zeng J, Zheng N, Wang J, Yuan L, Ji A, Kochansky C, Tao L, Huang Y, Maes E, Barbero L, Contrepois K, Ferrari L, Fu Y, Johnson J, Jones B, Kansal M, Lu Y, Post N, Shen HH, Xue YY, Zhang YC, Biswas G, Cho SJ, Edmison A, Benson K, Abberley L, Azadeh M, Francis J, Garofolo F, Gupta S, Ivanova ID, Ishii-Watabe A, Karnik S, Kassim S, Kavetska O, Keller S, Kossary E, Li W, McCush F, Mendes DN, Abhari MR, Scheibner K, Sikorski T, Staack RF, Tabler E, Tang H, Wan K, Wang YM, Whale E, Yang L, Zimmer J, Bandukwala A, Du X, Kholmanskikh O, Gijsel SK, Wadhwa M, Xu J, Buoninfante A, Cludts I, Diebold S, Maxfield K, Mayer C, Pedras-Vasconcelos J, Abhari MR, Shubow S, Tanaka Y, Tounekti O, Verthelyi D, and Wagner L

Subjects
Humans, Mass Spectrometry methods, Biomarkers analysis, United States, Cell- and Tissue-Based Therapy, Genetic Therapy, Chromatography methods, White, Proteomics methods
Abstract

The 17 th Workshop on Recent Issues in Bioanalysis (17 th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17 th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Published
2024
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