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2. Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses

Author

Hirz, Taghreed, Mei, Shenglin, Sarkar, Hirak, Kfoury, Youmna, Wu, Shulin, Verhoeven, Bronte M., Subtelny, Alexander O., Zlatev, Dimitar V., Wszolek, Matthew W., Salari, Keyan, Murray, Evan, Chen, Fei, Macosko, Evan Z., Wu, Chin-Lee, Scadden, David T., Dahl, Douglas M., Baryawno, Ninib, Saylor, Philip J., Kharchenko, Peter V., and Sykes, David B.

Published
2023
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8. MP31-13 CLINICOPATHOLOGICAL DIFFERENCES BETWEEN ANTERIORLY LOCATED AND PERIPHERAL ZONE PROSTATIC LESIONS DETECTED ON PROSTATE MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING

Author

An, Clemens, primary, Velmahos, Constantine, additional, Hunter, Alexandra, additional, Piroz, Bahar, additional, Barney, Alfred, additional, Feng, Aileen, additional, Dahl, Douglas, additional, Kim, Michelle, additional, Wszolek, Matthew, additional, Salari, Keyan, additional, Zlatev, Dimitar, additional, Harisinghani, Mukesh, additional, Wu, Shulin, additional, Wu, Chin-Lee, additional, and Feldman, Adam, additional

Published
2024
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13. DETECTION, RISK STRATIFICATION, AND THERAPUETIC SELECTION FOR UPPER TRACT UROTHELIAL CARCINOMA WITH URINE-BASED COMPREHENSIVE GENOMIC PROFILING

Author

Yonover, Paul M., primary, Kaplinsky, Robert, additional, Cherry, Ava, additional, Yonover, Jaden, additional, Cohen, Justin J., additional, Salari, Keyan, additional, Feldman, Adam, additional, Sundi, Debasish, additional, Phillips, Kevin G., additional, Fischer, Daniel, additional, Mazzarella, Brian C., additional, Bicocca, Vincent T., additional, Ward, Ceressa T., additional, Levin, Trevor G., additional, Gray, Joe W., additional, Koppie, Theresa M., additional, and Agarwal, Gautum, additional

Published
2024
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18. Transcriptional mediators of treatment resistance in lethal prostate cancer

Author

He, Meng Xiao, Cuoco, Michael S., Crowdis, Jett, Bosma-Moody, Alice, Zhang, Zhenwei, Bi, Kevin, Kanodia, Abhay, Su, Mei-Ju, Ku, Sheng-Yu, Garcia, Maria Mica, Sweet, Amalia R., Rodman, Christopher, DelloStritto, Laura, Silver, Rebecca, Steinharter, John, Shah, Parin, Izar, Benjamin, Walk, Nathan C., Burke, Kelly P., Bakouny, Ziad, Tewari, Alok K., Liu, David, Camp, Sabrina Y., Vokes, Natalie I., Salari, Keyan, Park, Jihye, Vigneau, Sébastien, Fong, Lawrence, Russo, Joshua W., Yuan, Xin, Balk, Steven P., Beltran, Himisha, Rozenblatt-Rosen, Orit, Regev, Aviv, Rotem, Asaf, Taplin, Mary-Ellen, and Van Allen, Eliezer M.

Published
2021
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19. Supplementary Figure 2 from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction

Author

Salari, Keyan, primary, Sundi, Debasish, primary, Lee, Jason J., primary, Wu, Shulin, primary, Wu, Chin-Lee, primary, DiFiore, Gabrielle, primary, Yan, Q. Robert, primary, Pienkny, Andrew, primary, Lee, Chi K., primary, Oberlin, Daniel, primary, Barme, Greg, primary, Piser, Joel, primary, Kahn, Robert, primary, Collins, Edward, primary, Phillips, Kevin G., primary, Caruso, Vincent M., primary, Goudarzi, Mahdi, primary, Garcia-Ransom, Monica, primary, Lentz, Peter S., primary, Evans-Holm, Martha E., primary, MacBride, Andrew R., primary, Fischer, Daniel S., primary, Haddadzadeh, Iden J., primary, Mazzarella, Brian C., primary, Gray, Joe W., primary, Koppie, Theresa M., primary, Bicocca, Vincent T., primary, Levin, Trevor G., primary, Lotan, Yair, primary, and Feldman, Adam S., primary

Published
2023
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20. Data from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction

Author

Salari, Keyan, primary, Sundi, Debasish, primary, Lee, Jason J., primary, Wu, Shulin, primary, Wu, Chin-Lee, primary, DiFiore, Gabrielle, primary, Yan, Q. Robert, primary, Pienkny, Andrew, primary, Lee, Chi K., primary, Oberlin, Daniel, primary, Barme, Greg, primary, Piser, Joel, primary, Kahn, Robert, primary, Collins, Edward, primary, Phillips, Kevin G., primary, Caruso, Vincent M., primary, Goudarzi, Mahdi, primary, Garcia-Ransom, Monica, primary, Lentz, Peter S., primary, Evans-Holm, Martha E., primary, MacBride, Andrew R., primary, Fischer, Daniel S., primary, Haddadzadeh, Iden J., primary, Mazzarella, Brian C., primary, Gray, Joe W., primary, Koppie, Theresa M., primary, Bicocca, Vincent T., primary, Levin, Trevor G., primary, Lotan, Yair, primary, and Feldman, Adam S., primary

Published
2023
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21. Supplementary Figure 1 from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction

Author

Salari, Keyan, primary, Sundi, Debasish, primary, Lee, Jason J., primary, Wu, Shulin, primary, Wu, Chin-Lee, primary, DiFiore, Gabrielle, primary, Yan, Q. Robert, primary, Pienkny, Andrew, primary, Lee, Chi K., primary, Oberlin, Daniel, primary, Barme, Greg, primary, Piser, Joel, primary, Kahn, Robert, primary, Collins, Edward, primary, Phillips, Kevin G., primary, Caruso, Vincent M., primary, Goudarzi, Mahdi, primary, Garcia-Ransom, Monica, primary, Lentz, Peter S., primary, Evans-Holm, Martha E., primary, MacBride, Andrew R., primary, Fischer, Daniel S., primary, Haddadzadeh, Iden J., primary, Mazzarella, Brian C., primary, Gray, Joe W., primary, Koppie, Theresa M., primary, Bicocca, Vincent T., primary, Levin, Trevor G., primary, Lotan, Yair, primary, and Feldman, Adam S., primary

Published
2023
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22. Supplementary Tables 1-8 from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction

Author

Salari, Keyan, primary, Sundi, Debasish, primary, Lee, Jason J., primary, Wu, Shulin, primary, Wu, Chin-Lee, primary, DiFiore, Gabrielle, primary, Yan, Q. Robert, primary, Pienkny, Andrew, primary, Lee, Chi K., primary, Oberlin, Daniel, primary, Barme, Greg, primary, Piser, Joel, primary, Kahn, Robert, primary, Collins, Edward, primary, Phillips, Kevin G., primary, Caruso, Vincent M., primary, Goudarzi, Mahdi, primary, Garcia-Ransom, Monica, primary, Lentz, Peter S., primary, Evans-Holm, Martha E., primary, MacBride, Andrew R., primary, Fischer, Daniel S., primary, Haddadzadeh, Iden J., primary, Mazzarella, Brian C., primary, Gray, Joe W., primary, Koppie, Theresa M., primary, Bicocca, Vincent T., primary, Levin, Trevor G., primary, Lotan, Yair, primary, and Feldman, Adam S., primary

Published
2023
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23. Integrative genomic and functional profiling of the pancreatic cancer genome

Author

Shain, A, Salari, Keyan, Giacomini, Craig P, and Pollack, Jonathan R

Abstract

Abstract Background Pancreatic cancer is a deadly disease with a five-year survival of less than 5%. A better understanding of the underlying biology may suggest novel therapeutic targets. Recent surveys of the pancreatic cancer genome have uncovered numerous new alterations; yet systematic functional characterization of candidate cancer genes has lagged behind. To address this challenge, here we have devised a highly-parallel RNA interference-based functional screen to evaluate many genomically-nominated candidate pancreatic cancer genes simultaneously. Results For 185 candidate pancreatic cancer genes, selected from recurrently altered genomic loci, we performed a pooled shRNA library screen of cell growth/viability across 10 different cell lines. Knockdown-associated effects on cell growth were assessed by enrichment or depletion of shRNA hairpins, by hybridization to barcode microarrays. A novel analytical approach (COrrelated Phenotypes for On-Target Effects; COPOTE) was used to discern probable on-target knockdown, based on identifying different shRNAs targeting the same gene and displaying concordant phenotypes across cell lines. Knockdown data were integrated with genomic architecture and gene-expression profiles, and selected findings validated using individual shRNAs and/or independent siRNAs. The pooled shRNA library design delivered reproducible data. In all, COPOTE analysis identified 52 probable on-target gene-knockdowns. Knockdown of known oncogenes (KRAS, MYC, SMURF1 and CCNE1) and a tumor suppressor (CDKN2A) showed the expected contrasting effects on cell growth. In addition, the screen corroborated purported roles of PLEKHG2 and MED29 as 19q13 amplicon drivers. Most notably, the analysis also revealed novel possible oncogenic functions of nucleoporin NUP153 (ostensibly by modulating TGFβ signaling) and Kruppel-like transcription factor KLF5 in pancreatic cancer. Conclusions By integrating physical and functional genomic data, we were able to simultaneously evaluate many candidate pancreatic cancer genes. Our findings uncover new facets of pancreatic cancer biology, with possible therapeutic implications. More broadly, our study provides a general strategy for the efficient characterization of candidate genes emerging from cancer genome studies.

Published
2013

24. Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction

Author

Salari, Keyan, primary, Sundi, Debasish, additional, Lee, Jason J., additional, Wu, Shulin, additional, Wu, Chin-Lee, additional, DiFiore, Gabrielle, additional, Yan, Q. Robert, additional, Pienkny, Andrew, additional, Lee, Chi K., additional, Oberlin, Daniel, additional, Barme, Greg, additional, Piser, Joel, additional, Kahn, Robert, additional, Collins, Edward, additional, Phillips, Kevin G., additional, Caruso, Vincent M., additional, Goudarzi, Mahdi, additional, Garcia-Ransom, Monica, additional, Lentz, Peter S., additional, Evans-Holm, Martha E., additional, MacBride, Andrew R., additional, Fischer, Daniel S., additional, Haddadzadeh, Iden J., additional, Mazzarella, Brian C., additional, Gray, Joe W., additional, Koppie, Theresa M., additional, Bicocca, Vincent T., additional, Levin, Trevor G., additional, Lotan, Yair, additional, and Feldman, Adam S., additional

Published
2023
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25. Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer

Author

Schneider, Adam C., primary, Chandrasekar, Thenappan, additional, Bowler, Nicholas, additional, Fogg, Ryan, additional, Leong, Joon Yau, additional, Gusev, Andrew, additional, Rodgers, Linda H., additional, McCormick, Shelley R., additional, Dahl, Douglas M., additional, Efstathiou, Jason A., additional, Blute, Michael L., additional, Zietman, Anthony L., additional, Wu, Chin-Lee, additional, Smith, Matthew R., additional, Van Allen, Eliezer M., additional, Feldman, Adam S., additional, and Salari, Keyan, additional

Published
2023
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26. Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions.

Author

Mei, Shenglin, Alchahin, Adele M., Tsea, Ioanna, Kfoury, Youmna, Hirz, Taghreed, Jeffries, Nathan Elias, Zhao, Ting, Xu, Yanxin, Zhang, Hanyu, Sarkar, Hirak, Wu, Shulin, Subtelny, Alexander O., Johnsen, John Inge, Zhang, Yida, Salari, Keyan, Wu, Chin-Lee, Randolph, Mark A., Scadden, David T., Dahl, Douglas M., and Shin, John

Subjects
RENAL cell carcinoma, REGULATORY T cells, CYTOTOXIC T cells, BONE marrow, SPINAL cord compression
Abstract

Background: Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods: We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results: The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions: These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels. [ABSTRACT FROM AUTHOR]

Published
2024
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27. PD46-07 URINARY COMPREHENSIVE GENOMIC PROFILING AIDS IN DETECTION AND RISK PROGNOSIS OF UPPER TRACT UROTHELIAL CARCINOMA: A CASE-CONTROLLED COHORT STUDY

Author

Yonover, Paul, primary, Kaplinsky, Robert, additional, Salari, Keyan, additional, Feldman, Adam, additional, Sundi, Debasish, additional, Phillips, Kevin G., additional, Fisher, Daniel, additional, Cherry, Ava, additional, Mazzarella, Brian C., additional, Bicocca, Vincent T., additional, Gray, Joe, additional, Koppie, Theresa M., additional, Levin, Trevor G., additional, and Cohen, Justin, additional

Published
2023
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29. MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY

Author

Lotan, Yair, primary, Salari, Keyan, additional, Feldman, Adam, additional, Sundi, Debasish, additional, Lee, Jason J, additional, DiFiore, Gabrielle, additional, Poustchi, Hossein, additional, Khoshnia, Masoud, additional, Roshandel, Gholamreza, additional, Etemadi, Arash, additional, Goudarzi, Mahdi, additional, Lentz, Peter S., additional, Phillips, Kevin G., additional, Bicocca, Vincent T., additional, Koppie, Theresa M., additional, Gray, Joe W., additional, Levin, Trevor, additional, Malekzadeh, Reza, additional, Sheikh, Mahdi, additional, and Le Calvez-Kelm, Florence, additional

Published
2023
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30. Supplementary Figures 1-3 from Comparative Analyses of Chromosome Alterations in Soft-Tissue Metastases within and across Patients with Castration-Resistant Prostate Cancer

Author

Holcomb, Ilona N., primary, Young, Janet M., primary, Coleman, Ilsa M., primary, Salari, Keyan, primary, Grove, Douglas I., primary, Hsu, Li, primary, True, Lawrence D., primary, Roudier, Martine P., primary, Morrissey, Colm M., primary, Higano, Celestia S., primary, Nelson, Peter S., primary, Vessella, Robert L., primary, and Trask, Barbara J., primary

Published
2023
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33. Data from Comparative Analyses of Chromosome Alterations in Soft-Tissue Metastases within and across Patients with Castration-Resistant Prostate Cancer

Author

Holcomb, Ilona N., primary, Young, Janet M., primary, Coleman, Ilsa M., primary, Salari, Keyan, primary, Grove, Douglas I., primary, Hsu, Li, primary, True, Lawrence D., primary, Roudier, Martine P., primary, Morrissey, Colm M., primary, Higano, Celestia S., primary, Nelson, Peter S., primary, Vessella, Robert L., primary, and Trask, Barbara J., primary

Published
2023
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34. Supplementary Tables 1-6 from Comparative Analyses of Chromosome Alterations in Soft-Tissue Metastases within and across Patients with Castration-Resistant Prostate Cancer

Author

Holcomb, Ilona N., primary, Young, Janet M., primary, Coleman, Ilsa M., primary, Salari, Keyan, primary, Grove, Douglas I., primary, Hsu, Li, primary, True, Lawrence D., primary, Roudier, Martine P., primary, Morrissey, Colm M., primary, Higano, Celestia S., primary, Nelson, Peter S., primary, Vessella, Robert L., primary, and Trask, Barbara J., primary

Published
2023
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37. Supplementary Figure Legends 1-3 from Comparative Analyses of Chromosome Alterations in Soft-Tissue Metastases within and across Patients with Castration-Resistant Prostate Cancer

Author

Holcomb, Ilona N., primary, Young, Janet M., primary, Coleman, Ilsa M., primary, Salari, Keyan, primary, Grove, Douglas I., primary, Hsu, Li, primary, True, Lawrence D., primary, Roudier, Martine P., primary, Morrissey, Colm M., primary, Higano, Celestia S., primary, Nelson, Peter S., primary, Vessella, Robert L., primary, and Trask, Barbara J., primary

Published
2023
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40. Analysis of evolutionary dynamics and clonal architecture in prostate cancer

Author

Conway, Jake R., primary, Tewari, Alok K., additional, Camp, Sabrina Y., additional, Han, Seunghun, additional, Crowdis, Jett, additional, He, Meng Xiao, additional, Nyame, Yaw A., additional, AlDubayan, Saud H., additional, Schultz, Nikolaus, additional, Szallasi, Zoltan, additional, Pomerantz, Mark M., additional, Freedman, Matthew L., additional, Fong, Lawrence, additional, Nelson, Peter S., additional, Brown, Myles, additional, Salari, Keyan, additional, and Allen, Eliezer Van, additional

Published
2023
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42. Prostate cancer single-cell and spatial transcriptomic data analyses

Author

Hirz, Taghreed, Mei, Shenglin, Sarkar, Hirak, Kfoury, Youmna, Wu, Shulin, Verhoeven, Bronte M, Subtelny, Alexander O, Zlatev, Dimitar V., Wszolek, Matthew W., Salari, Keyan, Murray, Evan, Chen, Fei, Macosko, Evan Z., Wu, Chin-Lee, Scadden, David T, Dahl, Douglas M, Baryawno, Ninib, Saylor, Philip J, Kharchenko, Peter V, and Sykes, David B

Subjects
prostate cancer, spatial transcriptomic, tumor microenvironment, immune suppressive
Abstract

The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.

Published
2023
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48. Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

Author

Hirz, Taghreed, primary, Mei, Shenglin, additional, Sarkar, Hirak, additional, Kfoury, Youmna, additional, Wu, Shulin, additional, Verhoeven, Bronte, additional, Subtelny, Alexander, additional, Zlatev, Dimitar, additional, Wszolek, Matthew, additional, Salari, Keyan, additional, Murray, Evan, additional, Chen, Fei, additional, Macosko, Evan, additional, Wu, Chin-Lee, additional, Scadden, David, additional, Dahl, Douglas, additional, Baryawno, Ninib, additional, Saylor, Philip, additional, Kharchenko, Peter, additional, and Sykes, David, additional

Published
2022
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