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3. Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study

Author

Ahn, Wooin, Appel, Gerald, Appelbaum, Paul, Babayev, Revekka, Chan, Brenda, D’Agati, Vivette Denise, Dogra, Samitri, Fernandez, Hilda, Gharavi, Ali, Hines, William, Husain, Syed Ali, Jain, Namrata, Kiryluk, Krzysztof, Lin, Fangming, Marasa, Maddalena, Markowitz, Glen, Rasouly, Hila Milo, Mohan, Sumit, Mongera, Nicola, Nestor, Jordan, Nickolas, Thomas, Radhakrishnan, Jai, Rao, Maya, Sanna-Cherchi, Simone, Shirazian, Shayan, Stokes, Michael Barry, Uy, Natalie, Valeri, Anthony, Vena, Natalie, Foroncewicz, Bartosz, Moszczuk, Barbara, Mucha, Krzysztof, Perkowska-Ptasińska, Agnieszka, Ghiggeri, Gian Marco, Lugani, Francesca, Ambruzs, Josephine, Liapis, Helen, Baracco, Rossana, Jain, Amrish, Isa Ashoor, Aviles, Diego, Srivastava, Tarak, Ahn, Sun-Young, Devarajan, Prasad, Erkan, Elif, Claes, Donna, Stone, Hillarey, Mason, Sherene, Gbadegesin, Rasheed, Gomez-Mendez, Liliana, Yin, Hong (Julie), Cai, Yi, Jens, Goebel, Steinke, Julia, Weaver, Donald, Lane, Jerome, Cramer, Carl, Pan, Cindy, Paloian, Neil, Sreedharan, Rajasree, Selewski, David, Twombley, Katherine, Bowers, Corinna, Dreher, Mary, Kallash, Mahmoud, Mahan, John, Sharpe, Samantha, Al-Uzri, Amira, Iragorri, Sandra, Belsha, Craig, Alge, Joseph, Braun, Michael, Gomez, A.C., Wenderfer, Scott, Vasylyeva, Tetyana, Feig, Daniel, Fuentes, Gabriel Cara, Hannah, Melisha, Nester, Carla, Chishti, Aftab, Klein, Jon, Katsoufis, Chryso, Seeherunvong, Wacharee, Wong, Craig, Mathews, Nisha, Barcia, John, Swiatecka-Urban, Agnes, Bartosh, Sharon, Hunley, Tracy, Dharnidharka, Vikas, Gaut, Joseph, Laurin, Louis-Philippe, Royal, Virginie, Achanti, Anand, Budisavljevic, Milos, Self, Sally, Ghossein, Cybele, Peleg, Yonatan, Wadhwani, Shikha, Almaani, Salem, Ayoub, Isabelle, Nadasdy, Tibor, Parikh, Samir, Rovin, Brad, Chang, Anthony, Fatima, Huma, Julian, Bruce, Novak, Jan, Renfrow, Matthew, Rizk, Dana, Chen, Dhruti, Derebail, Vimal, Falk, Ronald, Gibson, Keisha, Hogan, Susan, Jain, Koyal, Jennette, J. Charles, Mottl, Amy, Poulton, Caroline, Saha, Manish Kanti, Fogo, Agnes, Sanghani, Neil, Kidd, Jason, Muthusamy, Selvaraj, Hou, Jean, Lemley, Kevin, Mika, Warren, Russo, Pierre, Denburg, Michelle, Kogon, Amy, Meyers, Kevin, Pradhan, Madhura, O’Toole, John, Sedor, John, Sethna, Christine, Vento, Suzanne, Atta, Mohamed, Bagnasco, Serena, Neu, Alicia, Sperati, John, Adler, Sharon, Dai, Tiane, Dukkipati, Ram, Fervenza, Fernando, Sethi, Sanjeev, Kaskel, Frederick, Brathwaite, Kaye, Reidy, Kimberly, Weisstuch, Joseph, Wu, Ming, Zhdanova, Olga, Heymann, Jurgen, Kopp, Jeffrey, Waldman, Meryl, Winkler, Cheryl, Krissberg, Jill, Lafayette, Richard, Fahmeedah, Kamal, Talley, Elizabeth, Hladunewich, Michelle, Parekh, Rulan, Avila-Casado, Carmen, Cattran, Daniel, Heather, Reich, Boll, Philip, Drexler, Yelena, Fornoni, Alessia, Blazius, Brooke, Hodgin, Jeffrey, Oliverio, Andrea, Hogan, Jon, Palmer, Matthew, Abromovitz, Blaise, Mortiz, Michael, Alpers, Charles, Jefferson, J. Ashley, Brown, Elizabeth, Sambandam, Kamal, Roehm, Bethany, Graff, John, Gillespie, Brenda, Kretzler, Matthias, Nast, Cynthia, Barisoni, Laura, Guay-Woodford, Lisa M., Wang, Chia-shi, Glenn, Dorey A., Helmuth, Margaret, Smith, Abigail R., Bomback, Andrew S., Canetta, Pietro A., Coppock, Gaia M., Khalid, Myda, Tuttle, Katherine R., Bou-Matar, Raed, Greenbaum, Larry A., Robinson, Bruce M., Holzman, Lawrence B., Smoyer, William E., Rheault, Michelle N., Gipson, Debbie, and Mariani, Laura H.

Published
2024
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4. Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis

Author

Mariani, Laura H., Eddy, Sean, AlAkwaa, Fadhl M., McCown, Phillip J., Harder, Jennifer L., Nair, Viji, Eichinger, Felix, Martini, Sebastian, Ademola, Adebowale D., Boima, Vincent, Reich, Heather N., El Saghir, Jamal, Godfrey, Bradley, Ju, Wenjun, Tanner, Emily C., Vega-Warner, Virginia, Wys, Noel L., Adler, Sharon G., Appel, Gerald B., Athavale, Ambarish, Atkinson, Meredith A., Bagnasco, Serena M., Barisoni, Laura, Brown, Elizabeth, Cattran, Daniel C., Coppock, Gaia M., Dell, Katherine M., Derebail, Vimal K., Fervenza, Fernando C., Fornoni, Alessia, Gadegbeku, Crystal A., Gibson, Keisha L., Greenbaum, Laurence A., Hingorani, Sangeeta R., Hladunewich, Michelle A., Hodgin, Jeffrey B., Hogan, Marie C., Holzman, Lawrence B., Jefferson, J. Ashley, Kaskel, Frederick J., Kopp, Jeffrey B., Lafayette, Richard A., Lemley, Kevin V., Lieske, John C., Lin, Jen-Jar, Menon, Rajarasee, Meyers, Kevin E., Nachman, Patrick H., Nast, Cynthia C., O’Shaughnessy, Michelle M., Otto, Edgar A., Reidy, Kimberly J., Sambandam, Kamalanathan K., Sedor, John R., Sethna, Christine B., Singer, Pamela, Srivastava, Tarak, Tran, Cheryl L., Tuttle, Katherine R., Vento, Suzanne M., Wang, Chia-shi, Ojo, Akinlolu O., Adu, Dwomoa, Gipson, Debbie S., Trachtman, Howard, and Kretzler, Matthias

Published
2023
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6. Association of Obesity With Kidney and Cardiac Outcomes Among Patients With Glomerular Disease: Findings From the Cure Glomerulonephropathy Network

Author

Zeitler, Evan M., primary, Glenn, Dorey A., additional, Hu, Yichun, additional, Falk, Ronald J., additional, Hogan, Susan L., additional, Mottl, Amy K., additional, Gharavi, Ali, additional, Greenbaum, Larry, additional, Rheault, Michelle, additional, Smoyer, William E., additional, Falk, Ronald, additional, Holzman, Lawrence B., additional, Gillespie, Brenda, additional, Robinson, Bruce, additional, Mariani, Laura, additional, Roy, Cindy, additional, Guay-Woodford, Lisa, additional, and Parsa, Afshin, additional

Published
2024
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8. APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis

Author

Zee, Jarcy, McNulty, Michelle T., Hodgin, Jeffrey B., Zhdanova, Olga, Hingorani, Sangeeta, Jefferson, Jonathan Ashley, Gibson, Keisha L., Trachtman, Howard, Fornoni, Alessia, Dell, Katherine M., Reich, Heather N., Bagnasco, Serena, Greenbaum, Larry A., Lafayette, Richard A., Gipson, Debbie S., Brown, Elizabeth, Kretzler, Matthias, Appel, Gerald, Sambandam, Kamalanathan K., Tuttle, Katherine R., Chen, Dhruti, Atkinson, Meredith A., Hogan, Marie C., Kaskel, Frederick J., Meyers, Kevin E., O’Toole, John, Srivastava, Tarak, Sethna, Christine B., Hladunewich, Michelle A., Lin, JJ, Nast, Cynthia C., Derebail, Vimal K., Patel, Jiten, Vento, Suzanne, Holzman, Lawrence B., Athavale, Ambarish M., Adler, Sharon G., Lemley, Kevin V., Lieske, John C., Hogan, Jonathan J., Gadegbeku, Crystal A., Fervenza, Fernando C., Wang, Chia-Shi, Matar, Raed Bou, Singer, Pamela, Kopp, Jeffrey B., Barisoni, Laura, and Sampson, Matthew G.

Published
2021
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9. Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

Author

Gharavi, Ali, Ahn, Wooin, Appel, Gerald B., Avasare, Rupali S., Babayev, Revekka, Batal, Ibrahim, Bomback, Andrew S., Brown, Eric, Campenot, Eric S., Canetta, Pietro, Chan, Brenda, D’Agati, Vivette D., Fernandez, Hilda, Foroncewicz, Bartosz, Ghiggeri, Gian Marco, Hines, William H., Jain, Namrata G., Kiryluk, Krzysztof, Lin, Fangming, Lugani, Francesca, Marasa, Maddalena, Markowitz, Glen, Mohan, Sumit, Mucha, Krzysztof, Nickolas, Thomas L., Radhakrishnan, Jai, Rao, Maya K., Regunathan-Shenk, Renu, Sanna-Cherchi, Simone, Santoriello, Dominick, Stokes, Michael B., Yu, Natalie, Valeri, Anthony M., Zviti, Ronald, Greenbaum, Larry A., Smoyer, William E., Al-Uzri, Amira, Ashoor, Isa, Aviles, Diego, Baracco, Rossana, Barcia, John, Bartosh, Sharon, Belsha, Craig, Braun, Michael C., Chishti, Aftab, Claes, Donna, Cramer, Carl, Davis, Keefe, Erkan, Elif, Feig, Daniel, Freundlich, Michael, Hanna, Melisha, Hidalgo, Guillermo, Jain, Amrish, Khalid, Myda, Kallash, Mahmoud, Lane, Jerome C., Mahan, John, Mathews, Nisha, Nester, Carla, Pan, Cynthia, Patel, Hiren, Revell, Adelaide, Sreedharan, Rajasree, Steinke, Julia, Wenderfer, Scott E., Wong, Craig S., Falk, Ronald, Cook, William, Derebail, Vimal, Fogo, Agnes, Gasim, Adil, Gehr, Todd, Harris, Raymond, Kidd, Jason, Laurin, Louis-Philippe, Pendergraft, Will, Pichette, Vincent, Powell, Thomas Brian, Renfrow, Matthew B., Royal, Virginie, Holzman, Lawrence B., Adler, Sharon, Alpers, Charles, Matar, Raed Bou, Brown, Elizabeth, Choi, Michael, Dell, Katherine M., Dukkipati, Ram, Fervenza, Fernando C., Fornoni, Alessia, Gadegbeku, Crystal, Gipson, Patrick, Hasely, Leah, Hingorani, Sangeeta, Hladunewich, Michelle A., Hogan, Jonathan, Jefferson, J. Ashley, Jhaveri, Kenar, Johnstone, Duncan B., Kaskel, Frederick, Kogan, Amy, Kopp, Jeffrey, Lemley, Kevin V., Dieguez, Laura Malaga, Meyers, Kevin, Neu, Alicia, O'Shaughnessy, Michelle Marie, O’Toole, John F., Parekh, Rulan, Reich, Heather, Reidy, Kimberly, Rondon, Helbert, Sambandam, Kamalanathan K., Sedor, John R., Selewski, David T., Sethna, Christine B., Schelling, Jeffrey, Sperati, John C., Swiatecka-Urban, Agnes, Trachtman, Howard, Tuttle, Katherine R., Weisstuch, Joseph, Zhdanova, Olga, Gillespie, Brenda, Gipson, Debbie S., Herreshoff, Emily, Kretzler, Matthias, Robinson, Bruce M., Mariani, Laura, Troost, Jonathan P., Wladkowski, Matthew, Guay-Woodford, Lisa M., Murphy, Shannon L., Mahan, John D., Srivastava, Tarak, Kogon, Amy J., Cai, Yi, Davis, T. Keefe, Gbadegesin, Rasheed A., Canetta, Pietro A., Nachman, Patrick H., Reeve, Bryce B., Wang, Chia-shi, and Bartosh, Sharon M.

Published
2020
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10. Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today

Author

Trachtman, Howard, primary, Desmond, Hailey, additional, Williams, Amanda L., additional, Mariani, Laura H., additional, Eddy, Sean, additional, Ju, Wenjun, additional, Barisoni, Laura, additional, Ascani, Heather K., additional, Uhlmann, Wendy R., additional, Spino, Cathie, additional, Holzman, Lawrence B., additional, Sedor, John R., additional, Gadegbeku, Crystal, additional, Subramanian, Lalita, additional, Lienczewski, Chrysta C., additional, Manieri, Tina, additional, Roberts, Scott J., additional, Gipson, Debbie S., additional, Kretzler, Matthias, additional, Massengill, Susan, additional, Lo, Layla, additional, Dell, Katherine, additional, O’Toole, John, additional, Sedor, John, additional, Martin, Blair, additional, Macumber, Ian, additional, Sharma, Silpa, additional, Srivastava, Tarak, additional, Markus, Kelsey, additional, Sethna, Christine, additional, Vento, Suzanne, additional, Canetta, Pietro, additional, Olabisi, Opeyemi, additional, Gbadegesin, Rasheed, additional, Smith, Maurice, additional, Greenbaum, Laurence, additional, Wang, Chia-shi, additional, Yun, Emily, additional, Adler, Sharon, additional, LaPage, Janine, additional, Amarah, Amatur, additional, Itteera, Mathew, additional, Atkinson, Meredith, additional, Williams, Miahje, additional, Lieske, John, additional, Hogan, Marie, additional, Fervenza, Fernando, additional, Selewski, David, additional, Alston, Cheryl, additional, Reidy, Kim, additional, Ross, Michael, additional, Kaskel, Frederick, additional, Flynn, Patricia, additional, Malaga-Dieguez, Laura, additional, Zhdanova, Olga, additional, Pehrson, Laura Jane, additional, Miranda, Melanie, additional, Almaani, Salem, additional, Roberts, Laci, additional, Lafayette, Richard, additional, Dave, Shiktij, additional, Lee, Iris, additional, Shah, Shweta, additional, Batla, Sadaf, additional, Reich, Heather, additional, Hladunewich, Michelle, additional, Ling, Paul, additional, Romano, Martin, additional, Brakeman, Paul, additional, Dylewski, James, additional, Rogers, Nathan, additional, McCarthy, Ellen, additional, Creed, Catherine, additional, Fornoni, Alessia, additional, Bandes, Miguel, additional, Mariani, Laura, additional, Modi, Zubin, additional, Williams, A., additional, Ni, Roxy, additional, Nachman, Patrick, additional, Rheault, Michelle, additional, Kowalski, Amy, additional, Rauwolf, Nicolas, additional, Derebail, Vimal, additional, Gibson, Keisha, additional, Froment, Anne, additional, Kelley, Sara, additional, Holzman, Lawrence, additional, Meyers, Kevin, additional, Kallem, Krishna, additional, Edwards, Aliya, additional, Sharma, Samin, additional, Roehm, Elizabeth, additional, Sambandam, Kamalanathan, additional, Brown, Elizabeth, additional, Hellewege, Jamie, additional, Jefferson, Ashley, additional, Hingorani, Sangeeta, additional, Tuttle, Katherine, additional, Manahan, Linda, additional, Pao, Emily, additional, Kuykendall, Kelli, additional, Lin, Jen Jar, additional, Dharnidharka, Vikas, additional, Gillespie, Brenda, additional, Salmon, Eloise, additional, Trachtman, Howard, additional, Mainieri, Tina, additional, Alter, Gabrielle, additional, Arbit, Michael, additional, Fermin, Damian, additional, Larkina, Maria, additional, Lienczewski, Chrysta, additional, Scherr, Rebecca, additional, Troost, Jonathan, additional, Williams, Amanda, additional, Zhai, Yan, additional, Kincaid, Colleen, additional, Li, Shengqian, additional, Li, Shannon, additional, Sampson, Matthew G., additional, Smith, Abigail, additional, Zee, Jarcy, additional, Avila-Casado, Carmen, additional, Bagnasco, Serena, additional, Bu, Lihong, additional, Caltharp, Shelley, additional, Cassol, Clarissa, additional, Demeke, Dawit, additional, Hassler, Jared, additional, Herlitz, Leal, additional, Hewitt, Stephen, additional, Hodgin, Jeff, additional, Holanda, Danni, additional, Kambham, Neeraja, additional, Lemley, Kevin, additional, Messias, Nidia, additional, Mikhailov, Alexei, additional, Moreno, Vanessa, additional, Najafian, Behzad, additional, Palmer, Matthew, additional, Rosenberg, Avi, additional, Royal, Virginie, additional, Sekulik, Miroslav, additional, Stokes, Barry, additional, Thomas, David, additional, Wu, Ming, additional, Yamashita, Michifumi, additional, Yin, Hong, additional, Zuo . Cochairs, Yiqin, additional, and Nast, Cynthia, additional

Published
2024
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11. Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons.

Author

Chen, Meifan, Geoffroy, Cédric G, Wong, Hetty N, Tress, Oliver, Nguyen, Mallorie T, Holzman, Lawrence B, Jin, Yishi, and Zheng, Binhai

Subjects
Central Nervous System, Axons, Cells, Cultured, Animals, Mice, MAP Kinase Kinase Kinases, Cell Proliferation, Gene Expression, Gene Knockout Techniques, Cells, Cultured
Abstract

Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons.

Published
2016

13. Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study

Author

Wang, Chia-shi, primary, Glenn, Dorey A., additional, Helmuth, Margaret, additional, Smith, Abigail R., additional, Bomback, Andrew S., additional, Canetta, Pietro A., additional, Coppock, Gaia M., additional, Khalid, Myda, additional, Tuttle, Katherine R., additional, Bou-Matar, Raed, additional, Greenbaum, Larry A., additional, Robinson, Bruce M., additional, Holzman, Lawrence B., additional, Smoyer, William E., additional, Rheault, Michelle N., additional, Gipson, Debbie, additional, Mariani, Laura H., additional, Ahn, Wooin, additional, Appel, Gerald, additional, Appelbaum, Paul, additional, Babayev, Revekka, additional, Chan, Brenda, additional, D'Agati, Vivette Denise, additional, Dogra, Samitri, additional, Fernandez, Hilda, additional, Gharavi, Ali, additional, Hines, William, additional, Husain, Syed Ali, additional, Jain, Namrata, additional, Kiryluk, Krzysztof, additional, Lin, Fangming, additional, Marasa, Maddalena, additional, Markowitz, Glen, additional, Rasouly, Hila Milo, additional, Mohan, Sumit, additional, Mongera, Nicola, additional, Nestor, Jordan, additional, Nickolas, Thomas, additional, Radhakrishnan, Jai, additional, Rao, Maya, additional, Sanna-Cherchi, Simone, additional, Shirazian, Shayan, additional, Stokes, Michael Barry, additional, Uy, Natalie, additional, Valeri, Anthony, additional, Vena, Natalie, additional, Foroncewicz, Bartosz, additional, Moszczuk, Barbara, additional, Mucha, Krzysztof, additional, Perkowska-Ptasińska, Agnieszka, additional, Ghiggeri, Gian Marco, additional, Lugani, Francesca, additional, Ambruzs, Josephine, additional, Liapis, Helen, additional, Baracco, Rossana, additional, Jain, Amrish, additional, Ashoor, Isa, additional, Aviles, Diego, additional, Srivastava, Tarak, additional, Ahn, Sun-Young, additional, Devarajan, Prasad, additional, Erkan, Elif, additional, Claes, Donna, additional, Stone, Hillarey, additional, Mason, Sherene, additional, Gbadegesin, Rasheed, additional, Gomez-Mendez, Liliana, additional, Yin, Hong (Julie), additional, Cai, Yi, additional, Jens, Goebel, additional, Steinke, Julia, additional, Weaver, Donald, additional, Lane, Jerome, additional, Cramer, Carl, additional, Pan, Cindy, additional, Paloian, Neil, additional, Sreedharan, Rajasree, additional, Selewski, David, additional, Twombley, Katherine, additional, Bowers, Corinna, additional, Dreher, Mary, additional, Kallash, Mahmoud, additional, Mahan, John, additional, Sharpe, Samantha, additional, Al-Uzri, Amira, additional, Iragorri, Sandra, additional, Belsha, Craig, additional, Alge, Joseph, additional, Braun, Michael, additional, Gomez, A.C., additional, Wenderfer, Scott, additional, Vasylyeva, Tetyana, additional, Feig, Daniel, additional, Fuentes, Gabriel Cara, additional, Hannah, Melisha, additional, Nester, Carla, additional, Chishti, Aftab, additional, Klein, Jon, additional, Katsoufis, Chryso, additional, Seeherunvong, Wacharee, additional, Wong, Craig, additional, Mathews, Nisha, additional, Barcia, John, additional, Swiatecka-Urban, Agnes, additional, Bartosh, Sharon, additional, Hunley, Tracy, additional, Dharnidharka, Vikas, additional, Gaut, Joseph, additional, Laurin, Louis-Philippe, additional, Royal, Virginie, additional, Achanti, Anand, additional, Budisavljevic, Milos, additional, Self, Sally, additional, Ghossein, Cybele, additional, Peleg, Yonatan, additional, Wadhwani, Shikha, additional, Almaani, Salem, additional, Ayoub, Isabelle, additional, Nadasdy, Tibor, additional, Parikh, Samir, additional, Rovin, Brad, additional, Chang, Anthony, additional, Fatima, Huma, additional, Julian, Bruce, additional, Novak, Jan, additional, Renfrow, Matthew, additional, Rizk, Dana, additional, Chen, Dhruti, additional, Derebail, Vimal, additional, Falk, Ronald, additional, Gibson, Keisha, additional, Hogan, Susan, additional, Jain, Koyal, additional, Jennette, J. Charles, additional, Mottl, Amy, additional, Poulton, Caroline, additional, Saha, Manish Kanti, additional, Fogo, Agnes, additional, Sanghani, Neil, additional, Kidd, Jason, additional, Muthusamy, Selvaraj, additional, Schelling, Jeffrey, additional, Hou, Jean, additional, Lemley, Kevin, additional, Mika, Warren, additional, Russo, Pierre, additional, Denburg, Michelle, additional, Kogon, Amy, additional, Meyers, Kevin, additional, Pradhan, Madhura, additional, O'Toole, John, additional, Sedor, John, additional, Sethna, Christine, additional, Vento, Suzanne, additional, Atta, Mohamed, additional, Bagnasco, Serena, additional, Neu, Alicia, additional, Sperati, John, additional, Adler, Sharon, additional, Dai, Tiane, additional, Dukkipati, Ram, additional, Fervenza, Fernando, additional, Sethi, Sanjeev, additional, Kaskel, Frederick, additional, Brathwaite, Kaye, additional, Reidy, Kimberly, additional, Weisstuch, Joseph, additional, Wu, Ming, additional, Zhdanova, Olga, additional, Heymann, Jurgen, additional, Kopp, Jeffrey, additional, Waldman, Meryl, additional, Winkler, Cheryl, additional, Krissberg, Jill, additional, Lafayette, Richard, additional, Fahmeedah, Kamal, additional, Talley, Elizabeth, additional, Hladunewich, Michelle, additional, Parekh, Rulan, additional, Avila-Casado, Carmen, additional, Cattran, Daniel, additional, Heather, Reich, additional, Boll, Philip, additional, Drexler, Yelena, additional, Fornoni, Alessia, additional, Blazius, Brooke, additional, Hodgin, Jeffrey, additional, Oliverio, Andrea, additional, Hogan, Jon, additional, Palmer, Matthew, additional, Abromovitz, Blaise, additional, Mortiz, Michael, additional, Alpers, Charles, additional, Jefferson, J. Ashley, additional, Brown, Elizabeth, additional, Sambandam, Kamal, additional, Roehm, Bethany, additional, Graff, John, additional, Nast, Cynthia, additional, Barisoni, Laura, additional, Gillespie, Brenda, additional, and Kretzler, Matthias, additional

Published
2023
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14. Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today

Author

Massengill, Susan, Lo, Layla, Dell, Katherine, O’Toole, John, Sedor, John, Martin, Blair, Macumber, Ian, Sharma, Silpa, Srivastava, Tarak, Markus, Kelsey, Sethna, Christine, Vento, Suzanne, Canetta, Pietro, Olabisi, Opeyemi, Gbadegesin, Rasheed, Smith, Maurice, Greenbaum, Laurence, Wang, Chia-shi, Yun, Emily, Adler, Sharon, LaPage, Janine, Amarah, Amatur, Itteera, Mathew, Atkinson, Meredith, Williams, Miahje, Lieske, John, Hogan, Marie, Fervenza, Fernando, Selewski, David, Alston, Cheryl, Reidy, Kim, Ross, Michael, Kaskel, Frederick, Flynn, Patricia, Malaga-Dieguez, Laura, Zhdanova, Olga, Pehrson, Laura Jane, Miranda, Melanie, Almaani, Salem, Roberts, Laci, Lafayette, Richard, Dave, Shiktij, Lee, Iris, Shah, Shweta, Batla, Sadaf, Reich, Heather, Hladunewich, Michelle, Ling, Paul, Romano, Martin, Brakeman, Paul, Dylewski, James, Rogers, Nathan, McCarthy, Ellen, Creed, Catherine, Fornoni, Alessia, Bandes, Miguel, Kretzler, Matthias, Mariani, Laura, Modi, Zubin, Williams, A., Ni, Roxy, Nachman, Patrick, Rheault, Michelle, Kowalski, Amy, Rauwolf, Nicolas, Derebail, Vimal, Gibson, Keisha, Froment, Anne, Kelley, Sara, Holzman, Lawrence, Meyers, Kevin, Kallem, Krishna, Edwards, Aliya, Sharma, Samin, Roehm, Elizabeth, Sambandam, Kamalanathan, Brown, Elizabeth, Hellewege, Jamie, Jefferson, Ashley, Hingorani, Sangeeta, Tuttle, Katherine, Manahan, Linda, Pao, Emily, Kuykendall, Kelli, Lin, Jen Jar, Dharnidharka, Vikas, Gillespie, Brenda, Salmon, Eloise, Trachtman, Howard, Mainieri, Tina, Alter, Gabrielle, Arbit, Michael, Desmond, Hailey, Eddy, Sean, Fermin, Damian, Ju, Wenjun, Larkina, Maria, Lienczewski, Chrysta, Scherr, Rebecca, Troost, Jonathan, Williams, Amanda, Zhai, Yan, Kincaid, Colleen, Li, Shengqian, Li, Shannon, Gadegbeku, Crystal, Barisoni, Laura, Sampson, Matthew G., Smith, Abigail, Zee, Jarcy, Avila-Casado, Carmen, Bagnasco, Serena, Bu, Lihong, Caltharp, Shelley, Cassol, Clarissa, Demeke, Dawit, Hassler, Jared, Herlitz, Leal, Hewitt, Stephen, Hodgin, Jeff, Holanda, Danni, Kambham, Neeraja, Lemley, Kevin, Messias, Nidia, Mikhailov, Alexei, Moreno, Vanessa, Najafian, Behzad, Palmer, Matthew, Rosenberg, Avi, Royal, Virginie, Sekulik, Miroslav, Stokes, Barry, Thomas, David, Wu, Ming, Yamashita, Michifumi, Yin, Hong, Zuo . Cochairs, Yiqin, Nast, Cynthia, Williams, Amanda L., Mariani, Laura H., Ascani, Heather K., Uhlmann, Wendy R., Spino, Cathie, Holzman, Lawrence B., Sedor, John R., Subramanian, Lalita, Lienczewski, Chrysta C., Manieri, Tina, Roberts, Scott J., and Gipson, Debbie S.

Published
2024
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15. Reproducibility and Feasibility of Strategies for Morphologic Assessment of Renal Biopsies Using the Nephrotic Syndrome Study Network Digital Pathology Scoring System

Author

Zee, Jarcy, Hodgin, Jeffrey B., Mariani, Laura H., Gaut, Joseph P., Palmer, Matthew B., Bagnasco, Serena M., Rosenberg, Avi Z., Hewitt, Stephen M., Holzman, Lawrence B., Gillespie, Brenda W., and Barisoni, Laura

Subjects
Nephrotic syndrome -- Diagnosis -- Care and treatment, Kidney biopsy -- Methods, Glomeruli -- Medical examination, Test reliability -- Evaluation, Health
Abstract

* Context.--Testing reproducibility is critical for the development of methodologies for morphologic assessment. Our previous study using the descriptor-based Nephrotic Syndrome Study Network Digital Pathology Scoring System (NDPSS) on glomerular images revealed variable reproducibility. Objective.--To test reproducibility and feasibility of alternative scoring strategies for digital morphologic assessment of glomeruli and explore use of alternative agreement statistics. Design.--The original NDPSS was modified (NDPSS1 and NDPSS2) to evaluate (1) independent scoring of each individual biopsy level, (2) use of continuous measures, (3) groupings of individual descriptors into classes and sub-classes prior to scoring, and (4) indication of pathologists' confidence/uncertainty for any given score. Three and 5 pathologists scored 157 and 79 glomeruli using the NDPSS1 and NDPSS2, respectively. Agreement was tested using conventional (Cohen [kappa]) and alternative (Gwet agreement coefficient 1 [[AC.sub.1]]) agreement statistics and compared with previously published data (original NDPSS). Results.--Overall, pathologists' uncertainty was low, favoring application of the Gwet [AC.sub.1]. Greater agreement was achieved using the Gwet [AC.sub.1] compared with the Cohen [kappa] across all scoring methodologies. Mean (standard deviation) differences in agreement estimates using the NDPSS1 and NDPSS2 compared with the single-level original NDPSS were -0.09 (0.17) and -0.17 (0.17), respectively. Using the Gwet [AC.sub.1], 79% of the original NDPSS descriptors had good or excellent agreement. Pathologist feedback indicated the NDPSS1 and NDPSS2 were time-consuming. Conclusions.--The NDPSS1 and NDPSS2 increased pathologists' scoring burden without improving reproducibility. Use of alternative agreement statistics was strongly supported. We suggest using the original NDPSS on whole slide images for glomerular morphology assessment and for guiding future automated technologies. (Arch Pathol Lab Med. 2018;142:613-625; doi: 10.5858/arpa.2017-0181-OA), In the setting of clinical trials and translational research, the morphologic evaluation of renal biopsies has progressively transitioned from use of conventional light microscopy to digital pathology on whole slide [...]

Published
2018
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19. Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome

Author

Hodgin, Jeffrey B., primary, Mariani, Laura H., additional, Zee, Jarcy, additional, Liu, Qian, additional, Smith, Abigail R., additional, Eddy, Sean, additional, Hartman, John, additional, Hamidi, Habib, additional, Gaut, Joseph P., additional, Palmer, Matthew B., additional, Nast, Cynthia C., additional, Chang, Anthony, additional, Hewitt, Stephen, additional, Gillespie, Brenda W., additional, Kretzler, Matthias, additional, Holzman, Lawrence B., additional, Barisoni, Laura, additional, Dell, K., additional, Sedor, J., additional, Schachere, M., additional, Negrey, J., additional, Lemley, K., additional, Lim, E., additional, Srivastava, T., additional, Garrett, A., additional, Sethna, C., additional, Laurent, K., additional, Canetta, P., additional, Pradhan, A., additional, Greenbaum, L., additional, Wang, C., additional, Kang, C., additional, Adler, S., additional, LaPage, J., additional, Athavale, A., additional, Itteera, M., additional, Atkinson, M., additional, Boynton, S., additional, Fervenza, F., additional, Hogan, M., additional, Lieske, J., additional, Chernitskiy, V., additional, Kaskel, F., additional, Ross, M., additional, Flynn, P., additional, Kopp, J., additional, Blake, J., additional, Trachtman, H., additional, Zhdanova, O., additional, Modersitzki, F., additional, Vento, S., additional, Bray, M., additional, Kelton, M., additional, Cooper, A., additional, Lafayette, R., additional, Mehta, K., additional, Gadegbeku, C., additional, Quinn-Boyle, S., additional, Hladunewich, M., additional, Reich, H., additional, Ling, P., additional, Romano, M., additional, Fornoni, A., additional, Bidot, C., additional, Kretzler, M., additional, Gipson, D., additional, Williams, A., additional, LaVigne, J., additional, Derebail, V., additional, Gibson, K., additional, Cole, E., additional, Ormond-Foster, J., additional, Holzman, L., additional, Meyers, K., additional, Kallem, K., additional, Swenson, A., additional, Sambandam, K., additional, Wang, Z., additional, Rogers, M., additional, Jefferson, A., additional, Hingorani, S., additional, Tuttle, K., additional, Lin, J.J., additional, Barisoni, L., additional, Bixler, J., additional, Desmond, H., additional, Eddy, S., additional, Fermin, D., additional, Gillespie, B., additional, Kurtz, V., additional, Larkina, M., additional, Lavigne, J., additional, Li, S., additional, Lienczewski, C.C., additional, Liu, J., additional, Mainieri, T., additional, Mariani, L., additional, Sampson, M., additional, Smith, A., additional, Zee, J., additional, Avila-Casado, Carmen, additional, Bagnasco, Serena, additional, Gaut, Joseph, additional, Hodgin, Jeff, additional, Lemley, Kevin, additional, Mariani, Laura, additional, Palmer, Matthew, additional, Rosenberg, Avi, additional, Royal, Virginie, additional, Thomas, David, additional, and Nast, Cynthia, additional

Published
2022
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22. Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance

Author

Tian, Xuefei, Kim, Jin Ju, Monkley, Susan M., Gotoh, Nanami, Nandez, Ramiro, Soda, Keita, Inoue, Kazunori, Balkin, Daniel M., Hassan, Hossam, Son, Sung Hyun, Lee, Yashang, Moeckel, Gilbert, Calderwood, David A., Holzman, Lawrence B., Critchley, David R., Zent, Roy, Reiser, Jochen, and Ishibe, Shuta

Subjects
Cytoskeletal proteins -- Identification and classification -- Properties, Physiological research, Glomerular filtration rate -- Research, Health care industry
Abstract

Podocytes are specialized actin-rich epithelial cells that line the kidney glomerular filtration barrier. The interface between the podocyte and the glomerular basement membrane requires integrins, and defects in either [α.sub.3] or [β.sub.1] integrin, or the [α.sub.3][β.sub.1] ligand laminin result in nephrotic syndrome in murine models. The large cytoskeletal protein talin1 is not only pivotal for integrin activation, but also directly links integrins to the actin cytoskeleton. Here, we found that mice lacking talin1 specifically in podocytes display severe proteinuria, foot process effacement, and kidney failure. Loss of talin1 in podocytes caused only a modest reduction in [β.sub.1] integrin activation, podocyte cell adhesion, and cell spreading; however, the actin cytoskeleton of podocytes was profoundly altered by the loss of talin1. Evaluation of murine models of glomerular injury and patients with nephrotic syndrome revealed that calpain-induced talin1 cleavage in podocytes might promote pathogenesis of nephrotic syndrome. Furthermore, pharmacologic inhibition of calpain activity following glomerular injury substantially reduced talin1 cleavage, albuminuria, and foot process effacement. Collectively, these findings indicate that podocyte talin1 is critical for maintaining the integrity of the glomerular filtration barrier and provide insight into the pathogenesis of nephrotic syndrome., Introduction The glomerular filtration barrier is composed of podocytes and fenestrated endothelial cells separated by a glomerular basement membrane (GBM), which together function to filter plasma to generate urine devoid [...]

Published
2014
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24. Detailed Quantification of Glomerular Structural Lesions Associates with Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome

Author

Hodgin, Jeffrey B., primary, Mariani, Laura H., additional, Zee, Jarcy, additional, Liu, Qian, additional, Smith, Abigail R., additional, Eddy, Sean, additional, Hartman, John, additional, Hamidi, Habib, additional, Gaut, Joseph P., additional, Palmer, Matthew B., additional, Nast, Cynthia C., additional, Chang, Anthony, additional, Hewitt, Stephen, additional, Gillespie, Brenda W., additional, Kretzler, Matthias, additional, Holzman, Lawrence B., additional, and Barisoni, Laura, additional

Published
2021
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25. Multidimensional Data Integration Identifies Tumor Necrosis Factor Activation in Nephrotic Syndrome: A Model for Precision Nephrology

Author

Mariani, Laura H., primary, Eddy, Sean, additional, AlAkwaa, Fadhl M., additional, McCown, Phillip J., additional, Harder, Jennifer L., additional, Martini, Sebastian, additional, Ademola, Adebowale D., additional, Boima, Vincent, additional, Reich, Heather N., additional, Eichinger, Felix, additional, Saghir, Jamal El, additional, Godfrey, Bradley, additional, Ju, Wenjun, additional, Nair, Viji, additional, Tanner, Emily, additional, Vega-Warner, Virginia, additional, Wys, Noel L., additional, Adler, Sharon G., additional, Appel, Gerald B., additional, Athavale, Ambarish, additional, Atkinson, Meredith A., additional, Bagnasco, Serena M., additional, Barisoni, Laura, additional, Brown, Elizabeth, additional, Cattran, Daniel C., additional, Dell, Katherine M., additional, Derebail, Vimal K., additional, Fervenza, Fernando C., additional, Fornoni, Alessia, additional, Gadegbeku, Crystal A., additional, Gibson, Keisha L., additional, Greenbaum, Larry A., additional, Hingorani, Sangeeta R., additional, Hladunewich, Michelle A., additional, Hodgin, Jeffrey B., additional, Hogan, Jonathan J., additional, Hogan, Marie, additional, Holzman, Lawrence B., additional, Jefferson, J. Ashley, additional, Kaskel, Frederick J., additional, Kopp, Jeffrey B., additional, Lafayette, Richard A., additional, Lemley, Kevin V., additional, Lieske, John C., additional, Lin, Jen-Jar, additional, Menon, Rajarasee, additional, Meyers, Kevin E., additional, Nachman, Patrick H., additional, Nast, Cynthia C., additional, Neu, Alicia M., additional, O’Shaughnessy, Michelle M., additional, Otto, Edgar A., additional, Reidy, Kimberly J., additional, Sambandam, Kamalanathan K., additional, Sedor, John R., additional, Sethna, Christine B., additional, Singer, Pamela, additional, Srivastava, Tarak, additional, Tran, Cheryl L., additional, Tuttle, Katherine R., additional, Vento, Suzanne, additional, Wang, Chia-shi, additional, Ojo, Akinlolu O., additional, Adu, Dwomoa, additional, Gipson, Debbie S., additional, Trachtman, Howard, additional, and Kretzler, Matthias, additional

Published
2021
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26. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes

Author

Soda, Keita, Balkin, Daniel M., Ferguson, Shawn M., Paradise, Summer, Milosevic, Ira, Giovedi, Silvia, Volpicelli-Daley, Laura, Tian, Xuefei, Wu, Yumei, Ma, Hong, Son, Sung Hyun, Zheng, Rena, Moeckel, Gilbert, Cremona, Ottavio, Holzman, Lawrence B., de Camilli, Pietro, and Ishibe, Shuta

Subjects
Gene expression -- Research, Kidneys -- Genetic aspects, Endocytosis -- Genetic aspects, Actin -- Properties, Epithelial cells -- Genetic aspects, Health care industry
Abstract

Podocytes are specialized cells that play an integral role in the renal glomerular filtration barrier via their foot processes. The foot processes form a highly organized structure, the disruption of which causes nephrotic syndrome. Interestingly, several similarities have been observed between mechanisms that govern podocyte organization and mechanisms that mediate neuronal synapse development. Dynamin, synaptojanin, and endophilin are functional partners in synaptic vesicle recycling via interconnected actions in clathrin-mediated endocytosis and actin dynamics in neurons. A role of dynamin in the maintenance of the kidney filtration barrier via an action on the actin cytoskeleton of podocytes was suggested. Here we used a conditional double-KO of dynamin 1 (Dnm1) and Dnm2 in mouse podocytes to confirm dynamin's role in podocyte foot process maintenance. In addition, we demonstrated that while synaptojanin 1 (Synj1) KO mice and endophilin 1 (Sh3gl2), endophilin 2 (Sh3gl1), and endophilin 3 (Sh3gl3) triple-KO mice had grossly normal embryonic development, these mutants failed to establish a normal filtration barrier and exhibited severe proteinuria due to abnormal podocyte foot process formation. These results strongly implicate a protein network that functions at the interface between endocytosis and actin at neuronal synapses in the formation and maintenance of the kidney glomerular filtration barrier., Introduction Nephrotic syndrome is a severe kidney disease involving massive protein loss in the urine due to an impairment of the glomerular filtration barrier between the blood and the urinary [...]

Published
2012
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27. Crk 1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease

Author

George, Britta, Verma, Rakesh, Soofi, Abdulsalam A., Garg, Puneet, Zhang, Jidong, Park, Tae-Ju, Giardino, Laura, Ryzhova, Larisa, Johnstone, Duncan B., Wong, Hetty, Nihalani, Deepak, Salant, David J., Hanks, Steven K., Curran, Tom, Rastaldi, Maria Pia, and Holzman, Lawrence B.

Subjects
Glomerulonephritis -- Diagnosis -- Care and treatment -- Research, Actin -- Physiological aspects -- Research, Cellular signal transduction -- Research, Health care industry
Abstract

The morphology of healthy podocyte foot processes is necessary for maintaining the characteristics of the kidney filtration barrier. In most forms of glomerular disease, abnormal filter barrier function results when podocytes undergo foot process spreading and retraction by remodeling their cytoskeletal architecture and intercellular junctions during a process known as effacement. The cell adhesion protein nephrin is necessary for establishing the morphology of the kidney podocyte in development by transducing from the specialized podocyte intercellular junction phosphorylation-mediated signals that regulate cytoskeletal dynamics. The present studies extend our understanding of nephrin function by showing that nephrin activation in cultured podocytes induced actin dynamics necessary for lamellipodial protrusion. This process required a PI3K-, Cas-, and Crk1/2-dependent signaling mechanism distinct from the previously described nephrin-Nck1/2 pathway necessary for assembly and polymerization of actin filaments. Our present findings also support the hypothesis that mechanisms governing lamellipodial protrusion in culture are similar to those used in vivo during foot process effacement in a subset of glomerular diseases. In mice, podocyte-specific deletion of Crk1/2 prevented foot process effacement in one model of podocyte injury and attenuated foot process effacement and associated proteinuria in a delayed fashion in a second model. In humans, focal adhesion kinase and Cas phosphorylation - markers of focal adhesion complex-mediated Crk-dependent signaling - was induced in minimal change disease and membranous nephropathy, but not focal segmental glomerulosclerosis. Together, these observations suggest that activation of a Cas-Crk1/2-dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases., Introduction When functioning properly in health, the kidney filtration barrier selectively prevents the passage of macromolecules from the blood compartment into the urinary space. Differentiated podocytes form a remarkable octopus-like [...]

Published
2012
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28. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice

Author

Inoki, Ken, Mori, Hiroyuki, Wang, Junying, Suzuki, Tsukasa, Hong, SungKi, Yoshida, Sei, Blattner, Simone M., Ikenoue, Tsuneo, Ruegg, Markus A., Hall, Michael N., Kwiatkowski, David J., Rastaldi, Maria P., Huber, Tobias B., Kretzler, Matthias, Holzman, Lawrence B., Wiggins, Roger C., and Guan, Kun-Liang

Subjects
Kiss L.P., Diabetic nephropathies, Health care industry
Abstract

Diabetic nephropathy (DN) is among the most lethal complications that occur in type 1 and type 2 diabetics. Podocyte dysfunction is postulated to be a critical event associated with proteinuria [...]

Published
2011
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29. Podocyte-specific overexpression of GLUT1 surprisingly reduces mesangial matrix expansion in diabetic nephropathy in mice

Author

Zhang, Hongyu, Schin, MaryLee, Saha, Jharna, Burke, Kathleen, Holzman, Lawrence B., Filipiak, Wanda, Saunders, Thomas, Xiang, Minghui, Heilig, Charles W., and Brosius, Frank C., III

Subjects
Gene expression -- Physiological aspects, Epithelial cells -- Genetic aspects, Diabetic neuropathies -- Development and progression, Vascular endothelial growth factor -- Properties, Biological sciences
Abstract

Increased expression of the facilitative glucose transporter, GLUT1, leads to glomerulopathy that resembles diabetic nephropathy, whereas prevention of enhanced GLUT1 expression retards nephropathy. While many of the GLUT1-mediated effects are likely due to mesangial cell effects, we hypothesized that increased GLUT 1 expression in podocytes also contributes to the progression of diabetic nephropathy. Therefore, we generated two podocyte-specific GLUT1 transgenic mouse lines (driven by a podocin promoter) on a db/m C57BLKS background. Progeny of the two founders were used to generate diabetic db/db and control db/m littermate mice. Immunoblots of glomerular lysates showed that transgenic mice had a 3.5-fold (line 1) and 2.1-fold (line 2) increase in GLUT1 content compared with wild-type mice. Both lines showed similar increases in fasting blood glucose and body weights at 24 wk of age compared with wild-type mice. Mesangial index (percent PAS-positive material in the mesangial tuft) increased 88% (line 1) and 75% (line 2) in the wild-type diabetic mice but only 48% (line 1) and 39% (line 2) in the diabetic transgenic mice (P < 0.05, transgenic vs. wild-type mice). This reduction in mesangial expansion was accompanied by a reduction in fibronectin accumulation, and vascular endothelial growth factor (VEGF) levels increased only half as much in the transgenic diabetic mice as in wild-type diabetic mice. Levels of nephrin, nephl, CD2AP, podocin, and GLUT4 were not significantly different in transgenic compared with wild-type mice. Taken together, increased podocyte GLUTI expression in diabetic mice does not contribute to early diabetic nephropathy; surprisingly, it protects against mesangial expansion and fibronectin accumulation possibly by blunting podocyte VEGF increases. metabolism; glucose; vascular endothelial growth factor; type 2 diabetes; diabetic complications doi: 10.1152/ajprenal.00021.2010.

Published
2010

30. Ablation of developing podocytes disrupts cellular interactions and nephrogenesis both inside and outside the glomerulus

Author

Jia, Qunshan, McDill, Bradley W., Sankarapandian, Bala, Wu, Sen, Liapis, Helen, Holzman, Lawrence B., Capecchi, Mario R., Miner, Jeffrey H., and Chen, Feng

Subjects
Epithelial cells -- Physiological aspects, Epithelial cells -- Research, Cell interaction -- Research, Glomerulonephritis -- Risk factors, Biological sciences
Abstract

Podocyte loss in adults leads to glomerulosclerosis. However, the impact of podocyte loss on glomerulogenesis and the development of the kidney as a whole has not been directly studied. Here, we used a podocyte-specific Cre transgene to direct the production of diphtheria toxin (DTA) inside podocytes during nephrogenesis. Affected podocytes underwent translational arrest and apoptosis, leading to oliguria. proteinuria, hematuria, interstitial hemorrhage, and perinatal death. Glomerular cell-cell interactions were disrupted, even before overt podocyte apoptosis. VEGF production by podocytes was greatly decreased, and this was associated with reduced endothelial fenestration and altered glomerular vascular architecture. In addition to these glomerular anomalies, embryonic podocyte ablation also led to structural changes and increased apoptosis in proximal tubules. The collecting ducts, however, only showed molecular changes that are likely an indirect effect of the greatly reduced urine flow. Although podocyte loss significantly impacted the development and maintenance of the vasculature both inside and outside the glomerulus, our results suggest that there is a lack of long-range signaling from deep-seated, mature glomeruli to the differentiating cells in the outer nephrogenic zone. This study illustrates the tight integration of various cell types in the developing kidney and shows that the impact of podocyte loss during development is much greater than that in adults. This study also shows the specificity and effectiveness of a genetically controlled podocyte ablation system in mice where the additional readily available tools can further expand its applications. kidney development; glomerulogenesis; diphtheria toxin

Published
2008

31. Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization

Author

Verma, Rakesh, Kovari, Iulia, Soofi, Abdul, Nihalani, Deepak, Patrie, Kevin, and Holzman, Lawrence B.

Subjects
Kidneys -- Research, Medical research, Medicine, Experimental, Protein research
Abstract

A properly established and maintained podocyte intercellular junction, or slit diaphragm, is a necessary component of the selective permeability barrier of the kidney glomerulus. The observation that mutation or deletion [...]

Published
2006

33. An efficient system for tissue-specific overexpression of transgenes in podocytes in vivo

Author

Moeller, Marcus J., Soofi, Abdulsalam, Sanden, Silja, Floege, Jurgen, Kriz, Wilhelm, and Holzman, Lawrence B.

Subjects
Physiological research -- Analysis, Genetic research -- Analysis, Genetically modified mice -- Research, Genetically modified mice -- Genetic aspects, Genetically modified mice -- Physiological aspects, Biological sciences
Abstract

The utility of promoter fragments isolated from the 5'-flanking region of endogenous mammalian genes to drive transgene expression in vivo is often limited by low expression levels. In this study, a bigenic system was established that allows constitutive overexpression of transgenes in a tissue-specific fashion in transgenic mice in a time- and cost-effective fashion. A modified floxed expression vector was constructed [CMVflox-enhanced green fluorescent protein (eGFP)], in which a lacZ cassette ([beta]-galactosidase) flanked by lox sites was placed between a CMV-promoter and the transgene of interest (eGFP). Before Cre recombination, expression of eGFP was effectively prevented by the interposed floxed lacZ cassette, whereas [beta]-galactosidase was strongly expressed in transiently transfected cells. Transcription of the gene of interest (eGFP) could be irreversibly activated by cotransfection with Cre recombinase. Mice transgenic for CMV flox-eGFP were generated by pronuclear injection. A rapid assay was developed to identify transgenic founders with active transgene expression by measuring transgene activity ([beta]-galactosidase) in tail biopsies. Transgene activity in tails correlated with transgene expression in most other tissues tested including podocytes within the kidney. To activate expression of the gene of interest in a tissue-specific fashion, founder mice were mated to the Cre mouse line 2.5P-Cre previously shown to mediate 100% Cre recombination exclusively in podocytes (Moeller MJ, Sanden SK, Soofi A, Wiggins RC, and Holzman LB. Genesis 35: 39-42, 2003). In doubly transgenic offspring, high-level eGFP expression resulting from Cre excision of the interposed lacZ cassette was detected in four of seven CMVflox-eGFP founder lines. This approach should also circumvent common limitations arising from lethality or transgene silencing as a consequence of transgene overexpression. transgenic mouse; CMV promoter; kidney; loxP; Cre

Published
2005

37. Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

Author

Murphy, Shannon L., primary, Mahan, John D., additional, Troost, Jonathan P., additional, Srivastava, Tarak, additional, Kogon, Amy J., additional, Cai, Yi, additional, Davis, T. Keefe, additional, Fernandez, Hilda, additional, Fornoni, Alessia, additional, Gbadegesin, Rasheed A., additional, Herreshoff, Emily, additional, Canetta, Pietro A., additional, Nachman, Patrick H., additional, Reeve, Bryce B., additional, Selewski, David T., additional, Sethna, Christine B., additional, Wang, Chia-shi, additional, Bartosh, Sharon M., additional, Gipson, Debbie S., additional, Tuttle, Katherine R., additional, Gharavi, Ali, additional, Ahn, Wooin, additional, Appel, Gerald B., additional, Avasare, Rupali S., additional, Babayev, Revekka, additional, Batal, Ibrahim, additional, Bomback, Andrew S., additional, Brown, Eric, additional, Campenot, Eric S., additional, Canetta, Pietro, additional, Chan, Brenda, additional, D’Agati, Vivette D., additional, Foroncewicz, Bartosz, additional, Ghiggeri, Gian Marco, additional, Hines, William H., additional, Jain, Namrata G., additional, Kiryluk, Krzysztof, additional, Lin, Fangming, additional, Lugani, Francesca, additional, Marasa, Maddalena, additional, Markowitz, Glen, additional, Mohan, Sumit, additional, Mucha, Krzysztof, additional, Nickolas, Thomas L., additional, Radhakrishnan, Jai, additional, Rao, Maya K., additional, Regunathan-Shenk, Renu, additional, Sanna-Cherchi, Simone, additional, Santoriello, Dominick, additional, Stokes, Michael B., additional, Yu, Natalie, additional, Valeri, Anthony M., additional, Zviti, Ronald, additional, Greenbaum, Larry A., additional, Smoyer, William E., additional, Al-Uzri, Amira, additional, Ashoor, Isa, additional, Aviles, Diego, additional, Baracco, Rossana, additional, Barcia, John, additional, Bartosh, Sharon, additional, Belsha, Craig, additional, Braun, Michael C., additional, Chishti, Aftab, additional, Claes, Donna, additional, Cramer, Carl, additional, Davis, Keefe, additional, Erkan, Elif, additional, Feig, Daniel, additional, Freundlich, Michael, additional, Hanna, Melisha, additional, Hidalgo, Guillermo, additional, Jain, Amrish, additional, Khalid, Myda, additional, Kallash, Mahmoud, additional, Lane, Jerome C., additional, Mahan, John, additional, Mathews, Nisha, additional, Nester, Carla, additional, Pan, Cynthia, additional, Patel, Hiren, additional, Revell, Adelaide, additional, Sreedharan, Rajasree, additional, Steinke, Julia, additional, Wenderfer, Scott E., additional, Wong, Craig S., additional, Falk, Ronald, additional, Cook, William, additional, Derebail, Vimal, additional, Fogo, Agnes, additional, Gasim, Adil, additional, Gehr, Todd, additional, Harris, Raymond, additional, Kidd, Jason, additional, Laurin, Louis-Philippe, additional, Pendergraft, Will, additional, Pichette, Vincent, additional, Powell, Thomas Brian, additional, Renfrow, Matthew B., additional, Royal, Virginie, additional, Holzman, Lawrence B., additional, Adler, Sharon, additional, Alpers, Charles, additional, Matar, Raed Bou, additional, Brown, Elizabeth, additional, Choi, Michael, additional, Dell, Katherine M., additional, Dukkipati, Ram, additional, Fervenza, Fernando C., additional, Gadegbeku, Crystal, additional, Gipson, Patrick, additional, Hasely, Leah, additional, Hingorani, Sangeeta, additional, Hladunewich, Michelle A., additional, Hogan, Jonathan, additional, Jefferson, J. Ashley, additional, Jhaveri, Kenar, additional, Johnstone, Duncan B., additional, Kaskel, Frederick, additional, Kogan, Amy, additional, Kopp, Jeffrey, additional, Lemley, Kevin V., additional, Dieguez, Laura Malaga-, additional, Meyers, Kevin, additional, Neu, Alicia, additional, O'Shaughnessy, Michelle Marie, additional, O’Toole, John F., additional, Parekh, Rulan, additional, Reich, Heather, additional, Reidy, Kimberly, additional, Rondon, Helbert, additional, Sambandam, Kamalanathan K., additional, Sedor, John R., additional, Schelling, Jeffrey, additional, Sperati, John C., additional, Swiatecka-Urban, Agnes, additional, Trachtman, Howard, additional, Weisstuch, Joseph, additional, Zhdanova, Olga, additional, Gillespie, Brenda, additional, Kretzler, Matthias, additional, Robinson, Bruce M., additional, Mariani, Laura, additional, Wladkowski, Matthew, additional, and Guay-Woodford, Lisa M., additional

Published
2020
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38. Persistent Disease Activity in Patients With Long-Standing Glomerular Disease

Author

Delbarba, Elisa, primary, Marasa, Maddalena, additional, Canetta, Pietro A., additional, Piva, Stacy E., additional, Chatterjee, Debanjana, additional, Kil, Byum Hee, additional, Mu, Xueru, additional, Gibson, Keisha L., additional, Hladunewich, Michelle A., additional, Hogan, Jonathan J., additional, Julian, Bruce A., additional, Kidd, Jason M., additional, Laurin, Louis-Philippe, additional, Nachman, Patrick H., additional, Rheault, Michelle N., additional, Rizk, Dana V., additional, Sanghani, Neil S., additional, Trachtman, Howard, additional, Wenderfer, Scott E., additional, Gharavi, Ali G., additional, Bomback, Andrew S., additional, Ahn, Wooin, additional, Appel, Gerald B., additional, Babayev, Revekka, additional, Batal, Ibrahim, additional, Brown, Eric, additional, Campenot, Eric S., additional, Canetta, Pietro, additional, Chan, Brenda, additional, D’Agati, Vivette D., additional, Delbarba, Elisa, additional, Fernandez, Hilda, additional, Foroncewicz, Bartosz, additional, Ghiggeri, Gian Marco, additional, Hines, William H., additional, Jain, Namrata G., additional, Kiryluk, Krzysztof, additional, Lau, Wai L., additional, Lin, Fangming, additional, Lugani, Francesca, additional, Markowitz, Glen, additional, Mohan, Sumit, additional, Mucha, Krzysztof, additional, Nickolas, Thomas L., additional, Piva, Stacy, additional, Radhakrishnan, Jai, additional, Rao, Maya K., additional, Sanna-Cherchi, Simone, additional, Santoriello, Dominick, additional, Stokes, Michael B., additional, Yu, Natalie, additional, Valeri, Anthony M., additional, Zviti, Ronald, additional, Greenbaum, Larry A., additional, Smoyer, William E., additional, Al-Uzri, Amira, additional, Ashoor, Isa, additional, Aviles, Diego, additional, Baracco, Rossana, additional, Barcia, John, additional, Bartosh, Sharon, additional, Belsha, Craig, additional, Bowers, Corinna, additional, Braun, Michael C., additional, Chishti, Aftab, additional, Claes, Donna, additional, Cramer, Carl, additional, Davis, Keefe, additional, Erkan, Elif, additional, Feig, Daniel, additional, Freundlich, Michael, additional, Gbadegesin, Rasheed, additional, Hanna, Melisha, additional, Hidalgo, Guillermo, additional, Hunley, Tracy E., additional, Jain, Amrish, additional, Kallash, Mahmoud, additional, Khalid, Myda, additional, Klein, Jon B., additional, Lane, Jerome C., additional, Mahan, John, additional, Mathews, Nisha, additional, Nester, Carla, additional, Pan, Cynthia, additional, Patterson, Larry, additional, Patel, Hiren, additional, Revell, Adelaide, additional, Silva, Cynthia, additional, Sreedharan, Rajasree, additional, Srivastava, Tarak, additional, Steinke, Julia, additional, Twombley, Katherine, additional, Vasylyeva, Tetyana L., additional, Weaver, Donald J., additional, Wong, Craig S., additional, Almaani, Salem, additional, Ayoub, Isabelle, additional, Budisavljevic, Milos, additional, Derebail, Vimal, additional, Fatima, Huma, additional, Falk, Ronald, additional, Fogo, Agnes, additional, Gehr, Todd, additional, Gibson, Keisha, additional, Glenn, Dorey, additional, Harris, Raymond, additional, Hogan, Susan, additional, Jain, Koyal, additional, Jennette, J. Charles, additional, Julian, Bruce, additional, Kidd, Jason, additional, Massey, H. Davis, additional, Mottl, Amy, additional, Nachman, Patrick, additional, Nadasdy, Tibor, additional, Novak, Jan, additional, Parikh, Samir, additional, Pichette, Vincent, additional, Poulton, Caroline, additional, Powell, Thomas Brian, additional, Renfrow, Matthew, additional, Rizk, Dana, additional, Rovin, Brad, additional, Royal, Virginie, additional, Saha, Manish, additional, Sanghani, Neil, additional, Self, Sally, additional, Adler, Sharon, additional, Alpers, Charles, additional, Matar, Raed Bou, additional, Brown, Elizabeth, additional, Cattran, Daniel, additional, Choi, Michael, additional, Dell, Katherine M., additional, Dukkipati, Ram, additional, Fervenza, Fernando C., additional, Fornoni, Alessia, additional, Gadegbeku, Crystal, additional, Gipson, Patrick, additional, Hasely, Leah, additional, Hingorani, Sangeeta, additional, Hladunewich, Michelle, additional, Hogan, Jonathan, additional, Holzman, Lawrence B., additional, Jefferson, J. Ashley, additional, Jhaveri, Kenar, additional, Johnstone, Duncan B., additional, Kaskel, Frederick, additional, Kogan, Amy, additional, Kopp, Jeffrey, additional, Lafayette, Richard, additional, Lemley, Kevin V., additional, Malaga-Dieguez, Laura, additional, Meyers, Kevin, additional, Neu, Alicia, additional, O’Shaughnessy, Michelle Marie, additional, O’Toole, John F., additional, Parekh, Rulan, additional, Reich, Heather, additional, Reidy, Kimberly, additional, Rondon, Helbert, additional, Sambandam, Kamalanathan K., additional, Sedor, John R., additional, Selewski, David T., additional, Sethna, Christine B., additional, Schelling, Jeffrey, additional, Sperati, John C., additional, Swiatecka-Urban, Agnes, additional, Tuttle, Katherine R., additional, Weisstuch, Joseph, additional, Vento, Suzanne, additional, Zhdanova, Olga, additional, Gillespie, Brenda, additional, Gipson, Debbie S., additional, Hill-Callahan, Peg, additional, Helmuth, Margaret, additional, Herreshoff, Emily, additional, Kretzler, Matthias, additional, Lienczewski, Chrysta, additional, Mansfield, Sarah, additional, Mariani, Laura, additional, Nast, Cynthia C., additional, Robinson, Bruce M., additional, Troost, Jonathan, additional, Wladkowski, Matthew, additional, Zee, Jarcy, additional, Zinsser, Dawn, additional, and Guay-Woodford, Lisa M., additional

Published
2020
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42. Novel mouse embryonic renal marker gene products differentially expressed during kidney development

Author

Kretzler, Matthias, Fan, Guang, Rose, Demian, Arend, Lois J., Briggs, Josephine P., and Holzman, Lawrence B.

Subjects
Mice -- Genetic aspects, Genetic markers -- Usage, Kidneys -- Genetic aspects, Gene expression -- Analysis, Biological sciences
Abstract

A novel approach to study mouse renal organogenesis had been developed. This method used differential display polymerase chain reaction to survey gene expression in mouse kidney at embryonic day 11.5, 13.5, 15.5, and 17.5, and in the adult kidney. Twenty-two expression products were isolated. Sequencing analysis identified two as housekeeping gene products while three were similar to human or rat gene products. With these results, mouse embryonic renal markers were generated and analysed in mouse metanephric organ culture. The resulting pattern of gene expression was similar to that observed in vivo.

Published
1996

50. The motor protein Myo1c regulates transforming growth factor-β–signaling and fibrosis in podocytes

Author

Arif, Ehtesham, primary, Solanki, Ashish K., additional, Srivastava, Pankaj, additional, Rahman, Bushra, additional, Tash, Brian R., additional, Holzman, Lawrence B., additional, Janech, Michael G., additional, Martin, René, additional, Knölker, Hans-Joachim, additional, Fitzgibbon, Wayne R., additional, Deng, Peifeng, additional, Budisavljevic, Milos N., additional, Syn, Wing-Kin, additional, Wang, Cindy, additional, Lipschutz, Joshua H., additional, Kwon, Sang-Ho, additional, and Nihalani, Deepak, additional

Published
2019
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