Search

Your search keyword '"Kean, Leslie"' showing total 7 results
Start Over Author "Kean, Leslie" Publication Type Electronic Resources
7 results on '"Kean, Leslie"'

1. Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Author

Gorfinkel, Lev, Gorfinkel, Lev, Raghunandan, Sharmila, Watkins, Benjamin, Hebert, Kyle, Neuberg, Donna, Bratrude, Brandi, Betz, Kayla, Yu, Alison, Choi, Sung, Davis, Jeffrey, Duncan, Christine, Giller, Roger, Grimley, Michael, Harris, Andrew, Jacobsohn, David, Lalefar, Nahal, Farhadfar, Nosha, Pulsipher, Michael, Shenoy, Shalini, Petrovic, Aleksandra, Schultz, Kirk, Yanik, Gregory, Blazar, Bruce, Horan, John, Langston, Amelia, Kean, Leslie, Qayed, Muna, Gorfinkel, Lev, Gorfinkel, Lev, Raghunandan, Sharmila, Watkins, Benjamin, Hebert, Kyle, Neuberg, Donna, Bratrude, Brandi, Betz, Kayla, Yu, Alison, Choi, Sung, Davis, Jeffrey, Duncan, Christine, Giller, Roger, Grimley, Michael, Harris, Andrew, Jacobsohn, David, Lalefar, Nahal, Farhadfar, Nosha, Pulsipher, Michael, Shenoy, Shalini, Petrovic, Aleksandra, Schultz, Kirk, Yanik, Gregory, Blazar, Bruce, Horan, John, Langston, Amelia, Kean, Leslie, and Qayed, Muna

Abstract

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD (ocGVHD), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

Published
2024

2. Identification and Tracking of Alloreactive T Cell Clones in Rhesus Macaques Through the RM-scTCR-Seq Platform

Author

Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Gerdemann, Ulrike, Fleming, Ryan A, Kaminski, James, McGuckin, Connor, Rui, Xianliang, Lane, Jennifer F, Keskula, Paula, Cagnin, Lorenzo, Shalek, Alex K, Tkachev, Victor, Kean, Leslie S, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Gerdemann, Ulrike, Fleming, Ryan A, Kaminski, James, McGuckin, Connor, Rui, Xianliang, Lane, Jennifer F, Keskula, Paula, Cagnin, Lorenzo, Shalek, Alex K, Tkachev, Victor, and Kean, Leslie S

Abstract

T cell receptor (TCR) clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell’s transcriptional program with its TCR identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques (RM), a critical translational organism for autoimmune diseases, vaccine development and transplantation. We describe a new pipeline, ‘RM-scTCR-Seq’, which, for the first time, enables RM specific single cell TCR amplification, reconstruction and pairing of RM TCR’s with their transcriptional profiles. We apply this method to a RM model of GVHD, and identify and track in vitro detected alloreactive clonotypes in GVHD target organs and explore their GVHD driven cytotoxic T cell signature. This novel, state-of-the-art platform fundamentally advances the utility of RM to study protective and pathogenic T cell responses.

Published
2022

3. Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2021: Looking Forward as the Network Celebrates its 20th Year.

Author

Heslop, Helen E, Heslop, Helen E, Stadtmauer, Edward A, Levine, John E, Ballen, Karen K, Chen, Yi-Bin, DeZern, Amy E, Eapen, Mary, Hamadani, Mehdi, Hamilton, Betty K, Hari, Parameswaran, Jones, Richard J, Logan, Brent R, Kean, Leslie S, Leifer, Eric S, Locke, Frederick L, Maziarz, Richard T, Nemecek, Eneida R, Pasquini, Marcelo, Phelan, Rachel, Riches, Marcie L, Shaw, Bronwen E, Walters, Mark C, Foley, Amy, Devine, Steven M, Horowitz, Mary M, Heslop, Helen E, Heslop, Helen E, Stadtmauer, Edward A, Levine, John E, Ballen, Karen K, Chen, Yi-Bin, DeZern, Amy E, Eapen, Mary, Hamadani, Mehdi, Hamilton, Betty K, Hari, Parameswaran, Jones, Richard J, Logan, Brent R, Kean, Leslie S, Leifer, Eric S, Locke, Frederick L, Maziarz, Richard T, Nemecek, Eneida R, Pasquini, Marcelo, Phelan, Rachel, Riches, Marcie L, Shaw, Bronwen E, Walters, Mark C, Foley, Amy, Devine, Steven M, and Horowitz, Mary M

Abstract

In 2021 the BMT CTN held the 4th State of the Science Symposium where the deliberations of 11 committees concerning major topics pertinent to a particular disease, modality, or complication of transplant, as well as two committees to consider clinical trial design and inclusion, diversity, and access as cross-cutting themes were reviewed. This article summarizes the individual committee reports and their recommendations on the highest priority questions in hematopoietic stem cell transplant and cell therapy to address in multicenter trials.

Published
2021

4. Innovations present in the primate interneuron repertoire

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Krienen, Fenna M., Goldman, Melissa, Zhang, Qiangge, C. H. del Rosario, Ricardo, Florio, Marta, Machold, Robert, Saunders, Arpiar, Levandowski, Kirsten, Zaniewski, Heather, Schuman, Benjamin, Wu, Carolyn, Lutservitz, Alyssa, Mullally, Christopher D., Reed, Nora, Bien, Elizabeth, Bortolin, Laura, Fernandez-Otero, Marian, Lin, Jessica D., Wysoker, Alec, Nemesh, James, Kulp, David, Burns, Monika, Tkachev, Victor, Smith, Richard, Walsh, Christopher A., Dimidschstein, Jordane, Rudy, Bernardo, S. Kean, Leslie, Berretta, Sabina, Fishell, Gord, Feng, Guoping, McCarroll, Steven A., McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Krienen, Fenna M., Goldman, Melissa, Zhang, Qiangge, C. H. del Rosario, Ricardo, Florio, Marta, Machold, Robert, Saunders, Arpiar, Levandowski, Kirsten, Zaniewski, Heather, Schuman, Benjamin, Wu, Carolyn, Lutservitz, Alyssa, Mullally, Christopher D., Reed, Nora, Bien, Elizabeth, Bortolin, Laura, Fernandez-Otero, Marian, Lin, Jessica D., Wysoker, Alec, Nemesh, James, Kulp, David, Burns, Monika, Tkachev, Victor, Smith, Richard, Walsh, Christopher A., Dimidschstein, Jordane, Rudy, Bernardo, S. Kean, Leslie, Berretta, Sabina, Fishell, Gord, Feng, Guoping, and McCarroll, Steven A.

Abstract

Primates and rodents, which descended from a common ancestor around 90 million years ago , exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret). Homologous interneuron types—which were readily identified by their RNA-expression patterns—varied in abundance and RNA expression among ferrets, mice and primates, but varied less among primates. Only a modest fraction of the genes identified as ‘markers’ of specific interneuron subtypes in any one species had this property in another species. In the primate neocortex, dozens of genes showed spatial expression gradients among interneurons of the same type, which suggests that regional variation in cortical contexts shapes the RNA expression patterns of adult neocortical interneurons. We found that an interneuron type that was previously associated with the mouse hippocampus—the ‘ivy cell’, which has neurogliaform characteristics—has become abundant across the neocortex of humans, macaques and marmosets but not mice or ferrets. We also found a notable subcortical innovation: an abundant striatal interneuron type in primates that had no molecularly homologous counterpart in mice or ferrets. These interneurons expressed a unique combination of genes that encode transcription factors, receptors and neuropeptides and constituted around 30% of striatal interneurons in marmosets and humans.

Published
2021

5. Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.

Author

Kharfan-Dabaja, Mohamed A., Kumar, Ambuj, Ayala, Ernesto, Aljurf, Mahmoud, Nishihori, Taiga, Marsh, Rebecca, Burroughs, Lauri M., Majhail, Navneet, Al-Homsi, A. Samer, Al-Kadhimi, Zaid S., Bar, Merav, Bertaina, Alice, Boelens, Jaap J., Champlin, Richard, Chaudhury, Sonali, DeFilipp, Zachariah, Dholaria, Bhagirathbhai, El-Jawahri, Areej, Fanning, Suzanne, Fraint, Ellen, Gergis, Usama, Giralt, Sergio, Hamilton, Betty K., Hashmi, Shahrukh K., Horn, Biljana, Inamoto, Yoshihiro, Jacobsohn, David A., Jain, Tania, Johnston, Laura, Kanate, Abraham S., Kansagra, Ankit, Kassim, Adetola, Kean, Leslie S., Kitko, Carrie L., Knight-Perry, Jessica, Kurtzberg, Joanne, Liu, Hien, MacMillan, Margaret L., Mahmoudjafari, Zahra, Mielcarek, Marco, Mohty, Mohamad, Nagler, Arnon, Nemecek, Eneida, Olson, Timothy S., Oran, Betul, Perales, Miguel-Angel, Prockop, Susan E., Pulsipher, Michael A., Pusic, Iskra, Riches, Marcie L., Rodriguez, Cesar, Romee, Rizwan, Rondon, Gabriela, Saad, Ayman, Shah, Nina, Shaw, Peter J., Shenoy, Shalini, Sierra, Jorge, Talano, Julie, Verneris, Michael R., Veys, Paul, Wagner, John E., Savani, Bipin N., Hamadani, Mehdi, Carpenter, Paul A., Kharfan-Dabaja, Mohamed A., Kumar, Ambuj, Ayala, Ernesto, Aljurf, Mahmoud, Nishihori, Taiga, Marsh, Rebecca, Burroughs, Lauri M., Majhail, Navneet, Al-Homsi, A. Samer, Al-Kadhimi, Zaid S., Bar, Merav, Bertaina, Alice, Boelens, Jaap J., Champlin, Richard, Chaudhury, Sonali, DeFilipp, Zachariah, Dholaria, Bhagirathbhai, El-Jawahri, Areej, Fanning, Suzanne, Fraint, Ellen, Gergis, Usama, Giralt, Sergio, Hamilton, Betty K., Hashmi, Shahrukh K., Horn, Biljana, Inamoto, Yoshihiro, Jacobsohn, David A., Jain, Tania, Johnston, Laura, Kanate, Abraham S., Kansagra, Ankit, Kassim, Adetola, Kean, Leslie S., Kitko, Carrie L., Knight-Perry, Jessica, Kurtzberg, Joanne, Liu, Hien, MacMillan, Margaret L., Mahmoudjafari, Zahra, Mielcarek, Marco, Mohty, Mohamad, Nagler, Arnon, Nemecek, Eneida, Olson, Timothy S., Oran, Betul, Perales, Miguel-Angel, Prockop, Susan E., Pulsipher, Michael A., Pusic, Iskra, Riches, Marcie L., Rodriguez, Cesar, Romee, Rizwan, Rondon, Gabriela, Saad, Ayman, Shah, Nina, Shaw, Peter J., Shenoy, Shalini, Sierra, Jorge, Talano, Julie, Verneris, Michael R., Veys, Paul, Wagner, John E., Savani, Bipin N., Hamadani, Mehdi, and Carpenter, Paul A.

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.

Published
2021

6. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Koch Institute for Integrative Cancer Research at MIT, Ziegler, Carly G.K., Allon, Samuel J., Nyquist, Sarah K., Mbano, Ian M., Miao, Vincent N., Tzouanas, Constantine N., Cao, Yuming, Yousif, Ashraf S., Bals, Julia, Hauser, Blake M., Feldman, Jared, Muus, Christoph, Wadsworth, Marc H., Kazer, Samuel W., Hughes, Travis K., Doran, Benjamin, Gatter, G. James, Vukovic, Marko, Taliaferro, Faith, Mead, Benjamin E., Guo, Zhiru, Wang, Jennifer P., Gras, Delphine, Plaisant, Magali, Ansari, Meshal, Angelidis, Ilias, Adler, Heiko, Sucre, Jennifer M.S., Taylor, Chase J., Lin, Brian, Waghray, Avinash, Mitsialis, Vanessa, Dwyer, Daniel F., Buchheit, Kathleen M., Boyce, Joshua A., Barrett, Nora A., Laidlaw, Tanya M., Carroll, Shaina L., Colonna, Lucrezia, Tkachev, Victor, Peterson, Christopher W., Yu, Alison, Zheng, Hengqi Betty, Gideon, Hannah P., Winchell, Caylin G., Lin, Philana Ling, Bingle, Colin D., Snapper, Scott B., Kropski, Jonathan A., Theis, Fabian J., Schiller, Herbert B., Zaragosi, Laure-Emmanuelle, Barbry, Pascal, Leslie, Alasdair, Kiem, Hans-Peter, Flynn, JoAnne L., Fortune, Sarah M., Berger, Bonnie, Finberg, Robert W., Kean, Leslie S., Garber, Manuel, Schmidt, Aaron G., Lingwood, Daniel, Shalek, Alex K., Ordovas-Montanes, Jose, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Koch Institute for Integrative Cancer Research at MIT, Ziegler, Carly G.K., Allon, Samuel J., Nyquist, Sarah K., Mbano, Ian M., Miao, Vincent N., Tzouanas, Constantine N., Cao, Yuming, Yousif, Ashraf S., Bals, Julia, Hauser, Blake M., Feldman, Jared, Muus, Christoph, Wadsworth, Marc H., Kazer, Samuel W., Hughes, Travis K., Doran, Benjamin, Gatter, G. James, Vukovic, Marko, Taliaferro, Faith, Mead, Benjamin E., Guo, Zhiru, Wang, Jennifer P., Gras, Delphine, Plaisant, Magali, Ansari, Meshal, Angelidis, Ilias, Adler, Heiko, Sucre, Jennifer M.S., Taylor, Chase J., Lin, Brian, Waghray, Avinash, Mitsialis, Vanessa, Dwyer, Daniel F., Buchheit, Kathleen M., Boyce, Joshua A., Barrett, Nora A., Laidlaw, Tanya M., Carroll, Shaina L., Colonna, Lucrezia, Tkachev, Victor, Peterson, Christopher W., Yu, Alison, Zheng, Hengqi Betty, Gideon, Hannah P., Winchell, Caylin G., Lin, Philana Ling, Bingle, Colin D., Snapper, Scott B., Kropski, Jonathan A., Theis, Fabian J., Schiller, Herbert B., Zaragosi, Laure-Emmanuelle, Barbry, Pascal, Leslie, Alasdair, Kiem, Hans-Peter, Flynn, JoAnne L., Fortune, Sarah M., Berger, Bonnie, Finberg, Robert W., Kean, Leslie S., Garber, Manuel, Schmidt, Aaron G., Lingwood, Daniel, Shalek, Alex K., and Ordovas-Montanes, Jose

Abstract

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARSCoV- 2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit speciesspecific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Published
2020

7. Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality.

Author

Saha, Asim, Saha, Asim, O'Connor, Roddy S, Thangavelu, Govindarajan, Lovitch, Scott B, Dandamudi, Durga Bhavani, Wilson, Caleph B, Vincent, Benjamin G, Tkachev, Victor, Pawlicki, Jan M, Furlan, Scott N, Kean, Leslie S, Aoyama, Kazutoshi, Taylor, Patricia A, Panoskaltsis-Mortari, Angela, Foncea, Rocio, Ranganathan, Parvathi, Devine, Steven M, Burrill, Joel S, Guo, Lili, Sacristan, Catarina, Snyder, Nathaniel W, Blair, Ian A, Milone, Michael C, Dustin, Michael L, Riley, James L, Bernlohr, David A, Murphy, William J, Fife, Brian T, Munn, David H, Miller, Jeffrey S, Serody, Jonathan S, Freeman, Gordon J, Sharpe, Arlene H, Turka, Laurence A, Blazar, Bruce R, Saha, Asim, Saha, Asim, O'Connor, Roddy S, Thangavelu, Govindarajan, Lovitch, Scott B, Dandamudi, Durga Bhavani, Wilson, Caleph B, Vincent, Benjamin G, Tkachev, Victor, Pawlicki, Jan M, Furlan, Scott N, Kean, Leslie S, Aoyama, Kazutoshi, Taylor, Patricia A, Panoskaltsis-Mortari, Angela, Foncea, Rocio, Ranganathan, Parvathi, Devine, Steven M, Burrill, Joel S, Guo, Lili, Sacristan, Catarina, Snyder, Nathaniel W, Blair, Ian A, Milone, Michael C, Dustin, Michael L, Riley, James L, Bernlohr, David A, Murphy, William J, Fife, Brian T, Munn, David H, Miller, Jeffrey S, Serody, Jonathan S, Freeman, Gordon J, Sharpe, Arlene H, Turka, Laurence A, and Blazar, Bruce R

Abstract

Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1-/- donors. PD-L1-deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1-/- donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell-mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results