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28 results on '"Prakadan, Sanjay M."'

1. Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer

Author

Hamza, Bashar, Ng, Sheng Rong, Prakadan, Sanjay M., Delgado, Francisco Feijó, Chin, Christopher R., King, Emily M., Yang, Lucy F., Davidson, Shawn M., DeGouveia, Kelsey L., Cermak, Nathan, Navia, Andrew W., Winter, Peter S., Drake, Riley S., Tammela, Tuomas, Li, Carman Man-Chung, Papagiannakopoulos, Thales, Gupta, Alejandro J., Bagnall, Josephine Shaw, Knudsen, Scott M., Vander Heiden, Matthew G., Wasserman, Steven C., Jacks, Tyler, Shalek, Alex K., and Manalis, Scott R.

Published
2019

2. Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases

Author

Prakadan, Sanjay M., Alvarez-Breckenridge, Christopher A., Markson, Samuel C., Kim, Albert E., Klein, Robert H., Nayyar, Naema, Navia, Andrew W., Kuter, Benjamin M., Kolb, Kellie E., Bihun, Ivanna, Mora, Joana L., Bertalan, Mia Solana, Shaw, Brian, White, Michael, Kaplan, Alexander, Stocking, Jackson H., Wadsworth, II, Marc H., Lee, Eudocia Q., Chukwueke, Ugonma, Wang, Nancy, Subramanian, Megha, Rotem, Denisse, Cahill, Daniel P., Adalsteinsson, Viktor A., Miller, Jeffrey W., Sullivan, Ryan J., Carter, Scott L., Brastianos, Priscilla K., and Shalek, Alex K.

Published
2021
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3. Author Correction: Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases

Author

Prakadan, Sanjay M., Alvarez-Breckenridge, Christopher A., Markson, Samuel C., Kim, Albert E., Klein, Robert H., Nayyar, Naema, Navia, Andrew W., Kuter, Benjamin M., Kolb, Kellie E., Bihun, Ivanna, Mora, Joana L., Bertalan, Mia Solana, Shaw, Brian, White, Michael, Kaplan, Alexander, Stocking, Jackson H., Wadsworth, II, Marc H., Lee, Eudocia Q., Chukwueke, Ugonma, Wang, Nancy, Subramanian, Megha, Rotem, Denisse, Cahill, Daniel P., Adalsteinsson, Viktor A., Miller, Jeffrey W., Sullivan, Ryan J., Carter, Scott L., Brastianos, Priscilla K., and Shalek, Alex K.

Published
2021
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4. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

Author

Tirosh, Itay, Izar, Benjamin, Prakadan, Sanjay M., Wadsworth, Marc H., Treacy, Daniel, Trombetta, John J., Rotem, Asaf, Rodman, Christopher, Lian, Christine, Murphy, George, Fallahi-Sichani, Mohammad, Dutton-Regester, Ken, Lin, Jia-Ren, Cohen, Ofir, Shah, Parin, Lu, Diana, Genshaft, Alex S., Hughes, Travis K., Ziegler, Carly G. K., Kazer, Samuel W., Gaillard, Aleth, Kolb, Kellie E., Villani, Alexandra-Chloé, Johannessen, Cory M., Andreev, Aleksandr Y., Van Allen, Eliezer M., Bertagnolli, Monica, Sorger, Peter K., Sullivan, Ryan J., Flaherty, Keith T., Frederick, Dennie T., Jané-Valbuena, Judit, Yoon, Charles H., Rozenblatt-Rosen, Orit, Shalek, Alex K., Regev, Aviv, and Garraway, Levi A.

Published
2016

5. Supplementary Table 5 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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6. Supplementary Table 4 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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7. Supplementary Table 2 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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8. Data from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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9. Supplementary Table 6 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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10. Supplementary Table 3 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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11. Supplementary Table 7 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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12. Supplementary Table 1 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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13. Supplementary Figures and Methods from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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15. Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases

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, Massachusetts Institute of Technology. Computational and Systems Biology Program, Prakadan, Sanjay M, Alvarez-Breckenridge, Christopher A, Markson, Samuel C, Kim, Albert E, Klein, Robert H, Nayyar, Naema, Navia, Andrew W, Kuter, Benjamin M, Kolb, Kellie E, Bihun, Ivanna, Mora, Joana L, Bertalan, Mia Solana, Shaw, Brian, White, Michael, Kaplan, Alexander, Stocking, Jackson H, Wadsworth, Marc H, Lee, Eudocia Q, Chukwueke, Ugonma, Wang, Nancy, Subramanian, Megha, Rotem, Denisse, Cahill, Daniel P, Adalsteinsson, Viktor A, Miller, Jeffrey W, Sullivan, Ryan J, Carter, Scott L, Brastianos, Priscilla K, Shalek, Alex K, 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, Massachusetts Institute of Technology. Computational and Systems Biology Program, Prakadan, Sanjay M, Alvarez-Breckenridge, Christopher A, Markson, Samuel C, Kim, Albert E, Klein, Robert H, Nayyar, Naema, Navia, Andrew W, Kuter, Benjamin M, Kolb, Kellie E, Bihun, Ivanna, Mora, Joana L, Bertalan, Mia Solana, Shaw, Brian, White, Michael, Kaplan, Alexander, Stocking, Jackson H, Wadsworth, Marc H, Lee, Eudocia Q, Chukwueke, Ugonma, Wang, Nancy, Subramanian, Megha, Rotem, Denisse, Cahill, Daniel P, Adalsteinsson, Viktor A, Miller, Jeffrey W, Sullivan, Ryan J, Carter, Scott L, Brastianos, Priscilla K, and Shalek, Alex K

Abstract

AbstractLeptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research.

Published
2022

16. CANCER GENOMICS: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

Author

Tirosh, Itay, Izar, Benjamin, Prakadan, Sanjay M., Wadsworth, Marc H., II, Treacy, Daniel, Trombetta, John J., Rotem, Asaf, Rodman, Christopher, Lian, Christine, Murphy, George, Fallahi-Sichani, Mohammad, Dutton-Regester, Ken, Lin, Jia-Ren, Cohen, Ofir, Shah, Parin, Lu, Diana, Genshaft, Alex S., Hughes, Travis K., Ziegler, Carly G. K., Kazer, Samuel W., Gaillard, Aleth, Kolb, Kellie E., Villani, Alexandra-Chloé, Johannessen, Cory M., Andreev, Aleksandr Y., Van Allen, Eliezer M., Bertagnolli, Monica, Sorger, Peter K., Sullivan, Ryan J., Flaherty, Keith T., Frederick, Dennie T., Jané-Valbuena, Judit, Yoon, Charles H., Rozenblatt-Rosen, Orit, Shalek, Alex K., Regev, Aviv, and Garraway, Levi A.

Published
2016
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17. Mechanisms of lymphoma clearance induced by high-dose alkylating agents

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Ragon Institute of MGH, MIT and Harvard, Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E, Christie, Amanda L, van Scoyk, Alexandria, Prakadan, Sanjay M, Shigemori, Kay, Stevenson, Kristen E, Morrow, Sara, Plana, Olivia D, Fraser, Cameron, Jones, Kristen L, Liu, Huiyun, Pallasch, Christian P, Modiste, Rebecca, Nguyen, Quang-De, Craig, Jeffrey W, Morgan, Elizabeth A, Vega, Francisco, Aster, Jon C, Sarosiek, Kristopher A, Shalek, Alex K, Hemann, Michael T, Weinstock, David M, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Ragon Institute of MGH, MIT and Harvard, Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E, Christie, Amanda L, van Scoyk, Alexandria, Prakadan, Sanjay M, Shigemori, Kay, Stevenson, Kristen E, Morrow, Sara, Plana, Olivia D, Fraser, Cameron, Jones, Kristen L, Liu, Huiyun, Pallasch, Christian P, Modiste, Rebecca, Nguyen, Quang-De, Craig, Jeffrey W, Morgan, Elizabeth A, Vega, Francisco, Aster, Jon C, Sarosiek, Kristopher A, Shalek, Alex K, Hemann, Michael T, and Weinstock, David M

Abstract

© 2019 American Association for Cancer Research. The extraordinary activity of high-dose cyclophosphamide against some high-grade lymphomas was described nearly 60 years ago. Here we address mechanisms that mediate cyclophosphamide activity in bona fide human double-hit lymphoma. We show that antibody resistance within the bone marrow (BM) is not present upon early engraftment but develops during lymphoma progression. This resistance required a high tumor:macrophage ratio, was recapitulated in spleen by partial macrophage depletion, and was overcome by multiple, high-dose alkylating agents. Cyclophosphamide induced endoplasmic reticulum (ER) stress in BM-resident lymphoma cells in vivo that resulted in ATF4-mediated paracrine secretion of VEGFA, massive macrophage infiltration, and clearance of alemtuzumab-opsonized cells. BM macrophages isolated after cyclophosphamide treatment had increased phagocytic capacity that was reversed by VEGFA blockade or SYK inhibition. Single-cell RNA sequencing of these macrophages identified a “super-phagocytic” subset that expressed CD36/FCGR4. Together, these findings define a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance. SIGNIFICANCE: mAbs are effective against only a small subset of cancers. Herein, we recapitulate compartment-specific antibody resistance and define an ER stress–dependent mechanism induced by high-dose alkylating agents that promotes phagocytosis of opsonized tumor cells. This approach induces synergistic effects with mAbs and merits testing across additional tumor types.

Published
2021

18. MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection

Author

Khuzwayo, Sharon, primary, Mthembu, Maphe, additional, Meermeier, Erin W., additional, Prakadan, Sanjay M., additional, Kazer, Samuel W., additional, Bassett, Thierry, additional, Nyamande, Kennedy, additional, Khan, Dilshaad Fakey, additional, Maharaj, Priya, additional, Mitha, Mohammed, additional, Suleman, Moosa, additional, Mhlane, Zoey, additional, Ramjit, Dirhona, additional, Karim, Farina, additional, Shalek, Alex K., additional, Lewinsohn, David M., additional, Ndung’u, Thumbi, additional, and Wong, Emily B., additional

Published
2021
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19. MR1-restricted MAIT cells from the human lung mucosal surface have distinct phenotypic, functional, and transcriptomic features that are preserved in HIV infection

Author

Khuzwayo, Sharon, primary, Mthembu, Maphe, additional, Meermeier, Erin W., additional, Prakadan, Sanjay M., additional, Kazer, Samuel W., additional, Bassett, Thierry, additional, Nyamande, Kennedy, additional, Khan, Dilshaad Fakey, additional, Maharaj, Priya, additional, Mitha, Mohammed, additional, Suleman, Moosa, additional, Mhlane, Zoey, additional, Ramjit, Dirhona, additional, Karim, Farina, additional, Shalek, Alex K., additional, Lewinsohn, David M., additional, Ndung’u, Thumbi, additional, and Wong, Emily B., additional

Published
2020
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20. Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, additional, Kolb, Kellie E., additional, Christie, Amanda L., additional, Van Scoyk, Alexandria, additional, Prakadan, Sanjay M., additional, Shigemori, Kay, additional, Stevenson, Kristen E., additional, Morrow, Sara, additional, Plana, Olivia D., additional, Fraser, Cameron, additional, Jones, Kristen L., additional, Liu, Huiyun, additional, Pallasch, Christian P., additional, Modiste, Rebecca, additional, Nguyen, Quang-De, additional, Craig, Jeffrey W., additional, Morgan, Elizabeth A., additional, Vega, Francisco, additional, Aster, Jon C., additional, Sarosiek, Kristopher A., additional, Shalek, Alex K., additional, Hemann, Michael T., additional, and Weinstock, David M., additional

Published
2019
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21. Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E., Christie, Amanda L., Van Scoyk, Alexandria, Prakadan, Sanjay M., Shigemori, Kay, Stevenson, Kristen E., Morrow, Sara, Plana, Olivia D., Fraser, Cameron, Jones, Kristen L., Liu, Huiyun, Pallasch, Christian P., Modiste, Rebecca, Craig, Jeffrey W., Morgan, Elizabeth A., Vega, Francisco, Aster, Jon C., Sarosiek, Kristopher A., Shalek, Alex K., Hemann, Michael T., Weinstock, David M., Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E., Christie, Amanda L., Van Scoyk, Alexandria, Prakadan, Sanjay M., Shigemori, Kay, Stevenson, Kristen E., Morrow, Sara, Plana, Olivia D., Fraser, Cameron, Jones, Kristen L., Liu, Huiyun, Pallasch, Christian P., Modiste, Rebecca, Craig, Jeffrey W., Morgan, Elizabeth A., Vega, Francisco, Aster, Jon C., Sarosiek, Kristopher A., Shalek, Alex K., Hemann, Michael T., and Weinstock, David M.

Abstract

The extraordinary activity of high-dose cyclophosphamide against some high-grade lymphomas was described nearly 60 years ago. Here we address mechanisms that mediate cyclophosphamide activity in bona fide human double-hit lymphoma. We show that antibody resistance within the bone marrow (BM) is not present upon early engraftment but develops during lymphoma progression. This resistance required a high tumor:macrophage ratio, was recapitulated in spleen by partial macrophage depletion, and was overcome by multiple, high-dose alkylating agents. Cyclophosphamide induced endoplasmic reticulum (ER) stress in BM-resident lymphoma cells in vivo that resulted in ATF4-mediated paracrine secretion of VEGFA, massive macrophage infiltration, and clearance of alemtuzumab-opsonized cells. BM macrophages isolated after cyclophosphamide treatment had increased phagocytic capacity that was reversed by VEGFA blockade or SYK inhibition. Single-cell RNA sequencing of these macrophages identified a super-phagocytic subset that expressed CD36/FCGR4. Together, these findings define a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance. SIGNIFICANCE: mAbs are effective against only a small subset of cancers. Herein, we recapitulate compartment-specific antibody resistance and define an ER stress-dependent mechanism induced by high-dose alkylating agents that promotes phagocytosis of opsonized tumor cells. This approach induces synergistic effects with mAbs and merits testing across additional tumor types.

Published
2019

24. Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction

Author

Genshaft, Alex S., Li, Shuqiang, Gallant, Caroline J., Darmanis, Spyros, Prakadan, Sanjay M., Ziegler, Carly G. K., Lundberg, Martin, Fredriksson, Simon, Hong, Joyce, Regev, Aviv, Livak, Kenneth J., Landegren, Ulf, Shalek, Alex K., Genshaft, Alex S., Li, Shuqiang, Gallant, Caroline J., Darmanis, Spyros, Prakadan, Sanjay M., Ziegler, Carly G. K., Lundberg, Martin, Fredriksson, Simon, Hong, Joyce, Regev, Aviv, Livak, Kenneth J., Landegren, Ulf, and Shalek, Alex K.

Abstract

We present a scalable, integrated strategy for coupled protein and RNA detection from single cells. Our approach leverages the DNA polymerase activity of reverse transcriptase to simultaneously perform proximity extension assays and complementary DNA synthesis in the same reaction. Using the Fluidigm C1 (TM) system, we profile the transcriptomic and proteomic response of a human breast adenocarcinoma cell line to a chemical perturbation, benchmarking against in situ hybridizations and immunofluorescence staining, as well as recombinant proteins, ERCC Spike-Ins, and population lysate dilutions. Through supervised and unsupervised analyses, we demonstrate synergies enabled by simultaneous measurement of single-cell protein and RNA abundances. Collectively, our generalizable approach highlights the potential for molecular metadata to inform highly-multiplexed single-cell analyses.

Published
2016
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25. Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction

Author

Genshaft, Alex S, primary, Li, Shuqiang, additional, Gallant, Caroline J., additional, Darmanis, Spyros, additional, Prakadan, Sanjay M., additional, Ziegler, Carly G. K., additional, Lundberg, Martin, additional, Fredriksson, Simon, additional, Hong, Joyce, additional, Regev, Aviv, additional, Livak, Kenneth J., additional, Landegren, Ulf, additional, and Shalek, Alex K., additional

Published
2016
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26. Abstract CN07-04: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

Author

Tirosh, Itay, primary, Izar, Benjamin, additional, Prakadan, Sanjay M., additional, Wadsworth, Marc H., additional, Treacy, Daniel, additional, Trombetta, John J., additional, Lu, Diana, additional, Rotem, Asaf, additional, Lian, Christine, additional, Murphy, George, additional, Cohen, Ofir, additional, Allen, Eli van, additional, Bertagnolli, Monica, additional, Genshaft, Alex, additional, Hughes, Travis K., additional, Ziegler, Carly G. K., additional, Kazer, Samuel W., additional, Gaillard, Aleth, additional, Kolb, Kellie E., additional, Valbuena1, Judit, additional, Yoon, Charles, additional, Rozenblatt-Rosen, Orit, additional, Shalek, Alex K., additional, Regev, Aviv, additional, and Garraway, Levi, additional

Published
2015
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28. Chronic metabolic stress drives developmental programs and loss of tissue functions in non-transformed liver that mirror tumor states and stratify survival.

Author

Tzouanas CN, Sherman MS, Shay JES, Rubin AJ, Mead BE, Dao TT, Butzlaff T, Mana MD, Kolb KE, Walesky C, Pepe-Mooney BJ, Smith CJ, Prakadan SM, Ramseier ML, Tong EY, Joung J, Chi F, McMahon-Skates T, Winston CL, Jeong WJ, Aney KJ, Chen E, Nissim S, Zhang F, Deshpande V, Lauer GM, Yilmaz ÖH, Goessling W, and Shalek AK

Abstract

Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear. Namely, we do not know which pathways and programs define cellular responses, what regulatory factors mediate (mal)adaptations, and how this aberrant activity connects to tissue-scale dysfunction and long-term disease outcomes. Here, by applying longitudinal single-cell multi -omics to a mouse model of chronic metabolic stress and extending to human cohorts, we show that stress drives survival-linked tradeoffs and metabolic rewiring, manifesting as shifts towards development-associated states in non-transformed hepatocytes with accompanying decreases in their professional functionality. Diet-induced adaptations occur significantly prior to tumorigenesis but parallel tumorigenesis-induced phenotypes and predict worsened human cancer survival. Through the development of a multi -omic computational gene regulatory inference framework and human in vitro and mouse in vivo genetic perturbations, we validate transcriptional (RELB, SOX4) and metabolic (HMGCS2) mediators that co-regulate and couple the balance between developmental state and hepatocyte functional identity programming. Our work defines cellular features of liver adaptation to chronic stress as well as their links to long-term disease outcomes and cancer hallmarks, unifying diverse axes of cellular dysfunction around core causal mechanisms., Competing Interests: Competing Interests A.K.S. reports compensation for consulting and/or SAB membership from Honeycomb Biotechnologies, Cellarity, Ochre Bio, FL86, Relation Therapeutics, Senda Biosciences, IntrECate biotherapeutics, Bio-Rad Laboratories, and Dahlia Biosciences unrelated to this work. C.N.T., M.S.S., J.E.S., Ö.H.Y., W.G., and A.K.S have filed a patent related to this work.

Published
2023
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