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Assistant Professor
My laboratory is mainly focused on the immune regulatory mechanisms in human lymphoid malignancies, with a particular interest in signaling transduction pathways and ubiquitin-dependent non-proteolytic/proteolytic machineries in lymphoma pathogenesis. Gaining insight into the pathological roles of these regulatory pathways can lead to improved understanding of the molecular circuitry that drives tumor survival and shapes the tumor microenvironment, as well as providing novel intervention strategies for targeted therapy and immunotherapy.
Immune Signaling and Regulatory Pathways in Lymphoid Malignancies
A deep knowledge of cellular immunology has accelerated our understanding of the molecular circuitry that drives human lymphoid malignancies, including common mechanisms of signaling, transcriptional regulation, and survival. Functional cancer genomics using high-throughput library screens have provided the foundation for molecular, cellular and genetic approaches to investigate the role and function of specific genes and pathways in cancer biology, which is essential not only to understand the molecular basis of cancer but also to develop the means to target these pathways therapeutically.
Our laboratory is mainly focused on the immune regulatory pathways in human lymphoid malignancies. We are interested in the immune signaling pathways, particularly key transcriptional factors and ubiquitin-mediated signaling, required for lymphoma pathogenesis and immunotherapy. We have established multiple high-throughput screening technologies, as well as animal models to rapidly and accurately identify key pathways that are suitable for targeted therapy and immunotherapy. As such, our lab focuses on following interdisciplinary directions:
#1: Although the significance of tumor microenvironment in the pathogenesis of lymphoid malignancies is indisputable, our understanding of the connection between the signaling input from the tumor microenvironment and genetic alternations in malignant cells is still at an elementary stage. We have developed analytic pipelines in HL and ALCL Lymphoma, using high-throughput CRISPR library screen, next-generation sequencing (NGS) and lymphoma mice models, to discover deep oncogenic mechanisms for how immune regulatory and protein ubiquitination pathway regulate the micro-environmental signaling to support tumor cell survival.
#2: The success of PD1/PD-L1 based immunotherapy highlights the critical role played by PD-L1 in cancer progression, and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its level is controlled. Using CRISPR library screen technologies and animal models, we are pursuing a comprehensive understanding of the molecular effectors required for PD-L1 regulation in lymphoma, especially the novel transcriptional factors and ubiquitination enzymes. The findings will provide new strategies to improve immunotherapy efficacy.
#3: We have also established a drug sensitization screen platform using the CRISPR library screen technologies, and we have started to investigate the therapeutic potential and resistance mechanism of some of the most promising anti-lymphoma drugs based on the insights into lymphoma pathogenesis that have emerged from our laboratory. These translational research works provide the mechanistic understanding of how new drugs act in lymphoma, leading to the rational design of new clinical trials for lymphoma patients.
Positions are available for postdoctoral fellows and rotation students. For postdoctoral fellows, please forward a cover letter and updated CV to Dr. Yibin Yang (yibin.yang@fccc.edu). For rotation and summer students, please contact Dr. Yibin Yang (yibin.yang@fccc.edu) for additional details.
Song ZH, Wei W, Xiao W, Al-Saleem ED, Nejati R, Chen L, Yin J, Fabrizio J, Petrus MN, Waldmann TA, and Yang Y. Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2020 Nov 2;202014470. doi: 10.1073/pnas.2014470117; PMID: 33139544. PubMed
Wang H, Wei W, Zhang JP, Song ZH, Li Y, Xiao W, Liu Y, Zeng MS, Petrus MN, Thomas CJ, Kadin KE, Nakagawa M, Waldmann TA, and Yang Y. A novel model of alternative NF-kB pathway activation in anaplastic large cell lymphoma. Leukemia. 2020 Nov 12. doi: 10.1038/s41375-020-01088-y; PMID: 33184494. PubMed
Wei W, Lin Y, Song Z, Xiao W, Chen L, Yin J, Zhou Y, Barta SK, Petrus M, Waldmann TA, Yang Y. A20 and RBX1 regulate brentuximab vedotin sensitivity in Hodgkin Lymphoma models. Clin Cancer Res. 2020 Apr 16; doi: 10.1158/1078-0432. CCR-19-4137. PMID: 32299816; NIHMSID: NIHMS1585314. PubMed
Zhang JP, Song ZH, Wang H, Lang L, Yang YZ, Xiao W, Webster DE, Wei W, Barta S, Kadin ME, Staudt LM, Nakagawa M and Yang Y. A novel model of controlling PD-L1 expression in ALK+ Anaplastic Large Cell Lymphoma revealed by CRISPR screening. Blood. 2019 May 31. pii: blood.2019001043. PubMed
Pazina T, James AM, Colby KB, Yang Y, Gale A, Jhatakia A, Kearney A, Graziano RF, Bezman NA, Robbins MD, Cohen AD and Campbell KS. Elotuzumab enhances SLAMF7 interactions between natural killer and multiple myeloma cells to co-stimulate cytotoxicity. Cancer Immunol Res. 2019 Aug 20. pii: canimm.0579.2018. PubMed
Nakagawa M, Shaffer AL 3rd, Ceribelli M, Zhang M, Wright G, Huang DW, Xiao W, Powell J, Petrus MN, Yang Y, Phelan JD, Kohlhammer H, Dubois SP, Yoo HM, Bachy E, Webster DE, Yang Y, Xu W, Yu X, Zhao H, Bryant BR, Shimono J, Ishio T, Maeda M, Green PL, Waldmann TA, Staudt LM. Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma. Cancer Cell. 2018 Aug 13;34(2):286-297.e10. doi: 10.1016/j.ccell.2018.06.014. PMID:30057145. PubMed
Barta SK, Zain J, MacFarlane AW 4th, Smith SM, Ruan J, Fung HC, Tan CR, Yang Y, Alpaugh RK, Dulaimi E, Ross EA, Campbell KS, Khan N, Siddharta R, Fowler NH, Fisher R and Oki Y. Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2019 Apr 3. pii: S2152-2650(18)31750-6. PubMed
Somech R, Lev A, Lee YN, Simon AJ, Barel O, Schiby G, Avivi C, Barshack I, Rhodes M, Yin J, Wang M, Yang Y, Rhodes J, Marcus N, Garty BZ, Stein J, Amariglio N, Rechavi G, Wiest DL, Zhang Y. Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B. J Immunol. 2017 Dec 15;199(12):4036-4045. PubMed
Yang Y, Kelly P, Shaffer AL 3rd, Schmitz R, Yoo HM, Liu X, Huang da W, Webster D, Young RM, Nakagawa M, Ceribelli M, Wright GW, Yang Y, Zhao H, Yu X, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza L, Staudt LM. Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma. Cancer cell. 2016; 29(4):494-507. PubMed
Yang Y, Staudt LM. Protein ubiquitination in lymphoid malignancies. Immunol Rev. 2015 Jan;263(1):240-56. doi: 10.1111/imr.12247. PubMed
Yang Y, Schmitz R, Mitala J, Whiting A, Xiao W, Ceribelli M, Wright G, Zhao H, Yang Y, Xu W, Rosenwald A, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Wiestner A, Kruhlak MJ, Iwai K, Bernal F, and Staudt LM Essential Role of the Linear Ubiquitin Chain Assembly Complex in Lymphoma Revealed by Rare Germline Polymorphisms. Cancer Discovery. 2014 Apr;4(4):480-93. PubMed
Kelly PN, Romero DL, Yang Y, Shaffer AL 3rd, Chaudhary D, Robinson S, Miao W, Rui L, Weslin WF, Kapeller R, Staudt LM. Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy. J Exp Med. 2015 Nov 30. pii: jem.20151074. PubMed
Yang Y, Shaffer AL, Emre N.C, Ceribelli M, Zhang M, Wright G, Xiao W, Powell J, Platig J, Kohlhammer H, Young RM, Zhao H, Yang Y, Xu W, Buggy JJ, Balasubramanian S, Mathews LA, Shinn P, Guha R, Ferrer M, Thomas C, Waldmann TA, and Staudt LM Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma. Cancer Cell. 2012 Jun 12;21(6):723-37. PubMed
Ceribelli M, Kelly PN, Shaffer AL, Wright GW, Xiao W, Yang Y, Mathews Griner LA, Guha R, Shinn P, Keller JM, Liu D, Patel PR, Ferrer M, Joshi S, Nerle S, Sandy P, Normant E, Thomas CJ, Staudt LM. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. PNAS. 2014 Jul 21. pii: 201411701 PubMed
Lim KH, Yang Y, Staudt LM Pathogenetic importance and therapeutic implications of NF-kB in lymphoid malignancies. Immunol Rev. 2012 Mar;246(1):359-78. PubMed
yibin.yang@fccc.edu
Office Phone: 215-728-4746
Office: R363
Lab: R390
yibin.yang@fccc.edu
Office Phone: 215-728-4746
Office: R363
Lab: R390
Assistant Professor
My laboratory is mainly focused on the immune regulatory mechanisms in human lymphoid malignancies, with a particular interest in signaling transduction pathways and ubiquitin-dependent non-proteolytic/proteolytic machineries in lymphoma pathogenesis. Gaining insight into the pathological roles of these regulatory pathways can lead to improved understanding of the molecular circuitry that drives tumor survival and shapes the tumor microenvironment, as well as providing novel intervention strategies for targeted therapy and immunotherapy.
Immune Signaling and Regulatory Pathways in Lymphoid Malignancies
A deep knowledge of cellular immunology has accelerated our understanding of the molecular circuitry that drives human lymphoid malignancies, including common mechanisms of signaling, transcriptional regulation, and survival. Functional cancer genomics using high-throughput library screens have provided the foundation for molecular, cellular and genetic approaches to investigate the role and function of specific genes and pathways in cancer biology, which is essential not only to understand the molecular basis of cancer but also to develop the means to target these pathways therapeutically.
Our laboratory is mainly focused on the immune regulatory pathways in human lymphoid malignancies. We are interested in the immune signaling pathways, particularly key transcriptional factors and ubiquitin-mediated signaling, required for lymphoma pathogenesis and immunotherapy. We have established multiple high-throughput screening technologies, as well as animal models to rapidly and accurately identify key pathways that are suitable for targeted therapy and immunotherapy. As such, our lab focuses on following interdisciplinary directions:
#1: Although the significance of tumor microenvironment in the pathogenesis of lymphoid malignancies is indisputable, our understanding of the connection between the signaling input from the tumor microenvironment and genetic alternations in malignant cells is still at an elementary stage. We have developed analytic pipelines in HL and ALCL Lymphoma, using high-throughput CRISPR library screen, next-generation sequencing (NGS) and lymphoma mice models, to discover deep oncogenic mechanisms for how immune regulatory and protein ubiquitination pathway regulate the micro-environmental signaling to support tumor cell survival.
#2: The success of PD1/PD-L1 based immunotherapy highlights the critical role played by PD-L1 in cancer progression, and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its level is controlled. Using CRISPR library screen technologies and animal models, we are pursuing a comprehensive understanding of the molecular effectors required for PD-L1 regulation in lymphoma, especially the novel transcriptional factors and ubiquitination enzymes. The findings will provide new strategies to improve immunotherapy efficacy.
#3: We have also established a drug sensitization screen platform using the CRISPR library screen technologies, and we have started to investigate the therapeutic potential and resistance mechanism of some of the most promising anti-lymphoma drugs based on the insights into lymphoma pathogenesis that have emerged from our laboratory. These translational research works provide the mechanistic understanding of how new drugs act in lymphoma, leading to the rational design of new clinical trials for lymphoma patients.
Positions are available for postdoctoral fellows and rotation students. For postdoctoral fellows, please forward a cover letter and updated CV to Dr. Yibin Yang (yibin.yang@fccc.edu). For rotation and summer students, please contact Dr. Yibin Yang (yibin.yang@fccc.edu) for additional details.
Song ZH, Wei W, Xiao W, Al-Saleem ED, Nejati R, Chen L, Yin J, Fabrizio J, Petrus MN, Waldmann TA, and Yang Y. Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2020 Nov 2;202014470. doi: 10.1073/pnas.2014470117; PMID: 33139544. PubMed
Wang H, Wei W, Zhang JP, Song ZH, Li Y, Xiao W, Liu Y, Zeng MS, Petrus MN, Thomas CJ, Kadin KE, Nakagawa M, Waldmann TA, and Yang Y. A novel model of alternative NF-kB pathway activation in anaplastic large cell lymphoma. Leukemia. 2020 Nov 12. doi: 10.1038/s41375-020-01088-y; PMID: 33184494. PubMed
Wei W, Lin Y, Song Z, Xiao W, Chen L, Yin J, Zhou Y, Barta SK, Petrus M, Waldmann TA, Yang Y. A20 and RBX1 regulate brentuximab vedotin sensitivity in Hodgkin Lymphoma models. Clin Cancer Res. 2020 Apr 16; doi: 10.1158/1078-0432. CCR-19-4137. PMID: 32299816; NIHMSID: NIHMS1585314. PubMed
Zhang JP, Song ZH, Wang H, Lang L, Yang YZ, Xiao W, Webster DE, Wei W, Barta S, Kadin ME, Staudt LM, Nakagawa M and Yang Y. A novel model of controlling PD-L1 expression in ALK+ Anaplastic Large Cell Lymphoma revealed by CRISPR screening. Blood. 2019 May 31. pii: blood.2019001043. PubMed
Pazina T, James AM, Colby KB, Yang Y, Gale A, Jhatakia A, Kearney A, Graziano RF, Bezman NA, Robbins MD, Cohen AD and Campbell KS. Elotuzumab enhances SLAMF7 interactions between natural killer and multiple myeloma cells to co-stimulate cytotoxicity. Cancer Immunol Res. 2019 Aug 20. pii: canimm.0579.2018. PubMed
Nakagawa M, Shaffer AL 3rd, Ceribelli M, Zhang M, Wright G, Huang DW, Xiao W, Powell J, Petrus MN, Yang Y, Phelan JD, Kohlhammer H, Dubois SP, Yoo HM, Bachy E, Webster DE, Yang Y, Xu W, Yu X, Zhao H, Bryant BR, Shimono J, Ishio T, Maeda M, Green PL, Waldmann TA, Staudt LM. Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma. Cancer Cell. 2018 Aug 13;34(2):286-297.e10. doi: 10.1016/j.ccell.2018.06.014. PMID:30057145. PubMed
Barta SK, Zain J, MacFarlane AW 4th, Smith SM, Ruan J, Fung HC, Tan CR, Yang Y, Alpaugh RK, Dulaimi E, Ross EA, Campbell KS, Khan N, Siddharta R, Fowler NH, Fisher R and Oki Y. Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2019 Apr 3. pii: S2152-2650(18)31750-6. PubMed
Somech R, Lev A, Lee YN, Simon AJ, Barel O, Schiby G, Avivi C, Barshack I, Rhodes M, Yin J, Wang M, Yang Y, Rhodes J, Marcus N, Garty BZ, Stein J, Amariglio N, Rechavi G, Wiest DL, Zhang Y. Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B. J Immunol. 2017 Dec 15;199(12):4036-4045. PubMed
Yang Y, Kelly P, Shaffer AL 3rd, Schmitz R, Yoo HM, Liu X, Huang da W, Webster D, Young RM, Nakagawa M, Ceribelli M, Wright GW, Yang Y, Zhao H, Yu X, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza L, Staudt LM. Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma. Cancer cell. 2016; 29(4):494-507. PubMed
Yang Y, Staudt LM. Protein ubiquitination in lymphoid malignancies. Immunol Rev. 2015 Jan;263(1):240-56. doi: 10.1111/imr.12247. PubMed
Yang Y, Schmitz R, Mitala J, Whiting A, Xiao W, Ceribelli M, Wright G, Zhao H, Yang Y, Xu W, Rosenwald A, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Wiestner A, Kruhlak MJ, Iwai K, Bernal F, and Staudt LM Essential Role of the Linear Ubiquitin Chain Assembly Complex in Lymphoma Revealed by Rare Germline Polymorphisms. Cancer Discovery. 2014 Apr;4(4):480-93. PubMed
Kelly PN, Romero DL, Yang Y, Shaffer AL 3rd, Chaudhary D, Robinson S, Miao W, Rui L, Weslin WF, Kapeller R, Staudt LM. Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy. J Exp Med. 2015 Nov 30. pii: jem.20151074. PubMed
Yang Y, Shaffer AL, Emre N.C, Ceribelli M, Zhang M, Wright G, Xiao W, Powell J, Platig J, Kohlhammer H, Young RM, Zhao H, Yang Y, Xu W, Buggy JJ, Balasubramanian S, Mathews LA, Shinn P, Guha R, Ferrer M, Thomas C, Waldmann TA, and Staudt LM Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma. Cancer Cell. 2012 Jun 12;21(6):723-37. PubMed
Ceribelli M, Kelly PN, Shaffer AL, Wright GW, Xiao W, Yang Y, Mathews Griner LA, Guha R, Shinn P, Keller JM, Liu D, Patel PR, Ferrer M, Joshi S, Nerle S, Sandy P, Normant E, Thomas CJ, Staudt LM. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. PNAS. 2014 Jul 21. pii: 201411701 PubMed
Lim KH, Yang Y, Staudt LM Pathogenetic importance and therapeutic implications of NF-kB in lymphoid malignancies. Immunol Rev. 2012 Mar;246(1):359-78. PubMed