Y. Lynn Wang, MD, PhD, FCAP
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- Research Profile
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Clinical Locations
Primary Location
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Professor, Pathology
Specialties
Treatment Focus
Molecular diagnosis and classification of non-Hodgkin lymphoma
Research Program
Dr. Y. Lynn Wang, a board-certified molecular pathologist, is specialized in the development and interpretation of molecular and genomic clinical assays including PCR, RT-PCR, FISH, array CGH and next-gen sequencing assays. She has over 16 years of experience with many contributions to the medical and scientific literature. She served as the Founding Director of the Genomic and Molecular Pathology Division at the University of Chicago before she joined Fox Chase Cancer Center.
Twitter: @DrLynnWang
Educational Background
- MD, University of the State of New York, NY, 2002
- Postdoctoral Research, Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, 2000-02
- Residency, Clinical Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 1998-2002
- Fellowship, Molecular Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 1995-97
- PhD, Molecular Biology/Biochemistry, Department of Biochemistry, Brandeis University, Waltham, MA, 1995
- MD, Beijing Medical University (AKA Peking University Health Science Center), China, 1988
Certifications
- Certified in Clinical Pathology, American Board of Pathology
- Certified as a Laboratory Director in Genetic and Molecular Oncology Testing in the State of New York
- Certified as a Laboratory Director in Molecular Oncology Testing in the State of New York
- Certified in Molecular Genetic Pathology, American Board of Pathology/American College of Medical Genetics
- Re-certified in Molecular Genetic Pathology, American Board of Pathology/American College of Medical Genetics
Memberships
- American Society for Investigative Pathology
- American Society of Hematology
- Association for Molecular Pathology
- Elected Fellow, College of American Pathologists
- United States and Canadian Academy of Pathology
Honors & Awards
- Yao Yuan Award for Research Excellence, 2017
- Travel Award, American Society for Clinical Investigation, 2006, 2008
Research Program
Research Interests
ASH 2019: Distinct CLL cell populations provide rationale for combining drugs to minimize residual disease
At the American Society of Hematology Meeting in December 2019, Dr. Y. Lynn Wang gave an overview of her team’s chronic lymphocytic leukaemia proliferation model, which has demonstrated the benefits of combining ibrutinib and venetoclax. Video from ASH 2019 (December 8, 2019. 5:11)
Signaling pathways and molecular-targeted therapies in CLL and non-Hodgkin lymphoma
- B-cell receptor signaling in non-Hodgkin lymphoma and CLL
- Mechanisms of sensitivity and resistance to B-cell receptor-targeted therapies
- Molecular mechanisms of ibrutinib resistance in CLL and mantle cell lymphoma
Lab Overview
As a physician-scientist, Dr. Wang is the principal investigator of several translational research projects on aberrant signal transduction pathways in B-cell lymphoma and leukemia. Wang lab is one of the pioneering groups who explored the idea of targeting B-cell receptor (BCR) signaling in lymphoid malignancies before BCR-directed therapies became well-known and successful. The lab has shown that targeting specific components of the pathway blocked BCR signaling and generated anti-lymphoma effects. Detailed analyses of the downstream signaling cascades have enabled potential biomarker identification for therapeutic response prediction.
Interest of Wang Lab in BCR and BCR-targeted therapies has extended to the characterization of the molecular mechanisms underlying drug sensitivity and resistance. In particular, the lab contributed significantly to the understanding of the mechanisms leading to primary and secondary resistance to SYK and BTK inhibition. In May 2014, the lab reported the first discovery of BTKC481S mutation that confers ibrutinib (a BTK inhibitor) resistance in the NEJM. This has been followed by a series of studies elucidating the molecular mechanisms of primary and secondary resistance to ibrutinib in chronic lymphocytic leukemia and mantle cell lymphoma. The lab has also developed strategies for overcoming such resistance based on molecular rationales, such as using HSP90 inhibitors to overcome MYC activation in MCL. Many of the Wang lab projects involve collaborations with cytogenecists, structural biologists, hematopathologists, and heme/onc physicians.
Wang Lab has contributed ~70 papers to peer-reviewed medical and scientific literature. These include reports published in journals such as NEJM, Leukemia, JAMA Oncology, British Journal of Haematology, Oncogene, Blood and Blood Advances. Publications from Wang lab are read often with an annual citation of >250 each year since 2015 and their lymphoma research was highlighted and streamed online by OncoTV. Their article entitled “Functional characterization of BTKC481S mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors” is ranked as one of most highly cited papers published in Leukemia since 2015.
Additional Staff
Wenjun Wu, PhD, postdoctoral fellow
Vicky Wang, MD, PhD, visiting scholar
Ji Ma, MD, PhD, visiting scholar
Selected Publications
Lee J, Zhang LL, Wu W, Guo H, Li Y, Sukhanova M, Venkataraman G, Huang S, Zhang H, Alikhan M, Lu P, Guo A, Galanina N, Andrade J, Wang ML, Wang YL. Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma. Blood Adv; 2(16):2039-2051. 2018 PubMed
Ming M, Wu W, Xie B, Sukhanova M, Wang W, Kadri S, Sharma S, Lee J, Shacham S, Landesman Y, Maltsev N, Lu P, Wang YL. XPO1 Inhibitor Selinexor Overcomes Intrinsic Ibrutinib Resistance in Mantle Cell Lymphoma via Nuclear Retention of IκB. Mol Cancer Ther; 17(12):2564-2574. 2018 PubMed
Wang YL. MYD88 mutations and sensitivity to ibrutinib therapy. PMID:29482770. J Mol Diagn. 20:264-266, 2018 PubMed
Guo A, Lu P, Coffey G, Conley P, Pandey A, and Wang YL. Dual SYK/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: Cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment. Ongotarget, 8:12953-12967, 2017. PubMed
Guo A, Lu P, Lee J, Zhen CJ, Chiosis G, Wang YL. HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment. Oncogene 36:3441-9, 2017 PubMed
Kadri S, Lee J, Fitzpatrick C, Galanina N, Sukhanova M, Venkataraman G, Sharma S, Long B, Petras K, Theissen M, Ming M, Kobzev Y, Kang W, Guo A, Wang W, Niu N, Weiner H, Thirman M, Stock W, Smith SM, Nabhan, C, Segal JP, Lu P and Wang YL. Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL. Blood Advances 1:715-727, 2017 PubMed
Guo A, Lu P, Galanina N, Nabhan C, Smith SM, Coleman M, and Wang YL. Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib. PMID: 26717038. Oncotarget. 7: 4598-610, 2016 PubMed
Sharma S, Galanina N, Guo A, Lee J, Kadri S, Van Slambrouck C, Long B, Ming M, Furtado LV, Segal, JP, Stock W, Venkataraman G, Tang W-J, Lu P, and Wang YL. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. PMID: 27626698. Oncotarget.7:68833-41, 2016 PubMed
Cheng S, Guo A, Lu P, Ma J, Coleman M, and Wang YL. Functional Characterization of BTKC481S mutation that confers ibrutinib resistance: Exploration of alternative kinase inhibitors. PMID: 25189416. Leukemia. 29:895-900, 2015. Ranked as one of most highly cited papers published in Leukemia from 2015 in December 2017. PubMed
Zhang SQ, Smith SM, Zhang SY, and Wang YL. Mechanisms of ibrutinib resistance in chronic lymphocytic leukemia and non-Hodgkin lymphoma. PMID: 25858358. Br J Haematol. 170:445-56, 2015 PubMed
Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, Raca G, Pandey A, Conley P, Yu H and Wang YL. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. PMID: 26575169. Oncotarget. 6: 43881-96, 2015. PubMed
Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M, Liu M, Buggy JJ, Furman RR, and Wang YL. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. PMID:24270740. Leukemia, 28: 649-57, 2014. PubMed
Furman RR*, Cheng S*, Lu P*, Setty M, Perez A, Guo A, Racchumi J, Xu G, Ma J, Coleman M, Buggy J, Leslie C, and Wang YL. Ibrutinib resistance in chronic lymphocytic leukemia. PMID: 24869597. N Engl J Med. 370: 2352-4. 2014 *Co-first authors. PubMed
Ma J, Lu P, Guo A, Cheng S, Zong H, Martin P, Coleman M, and Wang YL. Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells. PMID:24957109. Br J Haematol. 166:849-61, 2014. PubMed
Cheng S, Coffey G, Zhang XH, Shaknovich R, Song Z, Lu P, Pandey A, Melnick AM, Sinha U and Wang YL. SYK inhibition and response prediction in diffuse large B-cell lymphoma. Blood. 118, 6342-52, 2011. PubMed
Additional Publications
Clinical Locations
Primary Location
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Contact Information
Phone: 215-728-3064
Email: yuelynn.wang@fccc.edu
Professor, Pathology
Specialties
Treatment Focus
Molecular diagnosis and classification of non-Hodgkin lymphoma
Research Program
Dr. Y. Lynn Wang, a board-certified molecular pathologist, is specialized in the development and interpretation of molecular and genomic clinical assays including PCR, RT-PCR, FISH, array CGH and next-gen sequencing assays. She has over 16 years of experience with many contributions to the medical and scientific literature. She served as the Founding Director of the Genomic and Molecular Pathology Division at the University of Chicago before she joined Fox Chase Cancer Center.
Twitter: @DrLynnWang
Education
Educational Background
- MD, University of the State of New York, NY, 2002
- Postdoctoral Research, Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, 2000-02
- Residency, Clinical Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 1998-2002
- Fellowship, Molecular Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 1995-97
- PhD, Molecular Biology/Biochemistry, Department of Biochemistry, Brandeis University, Waltham, MA, 1995
- MD, Beijing Medical University (AKA Peking University Health Science Center), China, 1988
Certifications
- Certified in Clinical Pathology, American Board of Pathology
- Certified as a Laboratory Director in Genetic and Molecular Oncology Testing in the State of New York
- Certified as a Laboratory Director in Molecular Oncology Testing in the State of New York
- Certified in Molecular Genetic Pathology, American Board of Pathology/American College of Medical Genetics
- Re-certified in Molecular Genetic Pathology, American Board of Pathology/American College of Medical Genetics
Memberships
- American Society for Investigative Pathology
- American Society of Hematology
- Association for Molecular Pathology
- Elected Fellow, College of American Pathologists
- United States and Canadian Academy of Pathology
Honors & Awards
- Yao Yuan Award for Research Excellence, 2017
- Travel Award, American Society for Clinical Investigation, 2006, 2008
Research Profile
Research Interests
ASH 2019: Distinct CLL cell populations provide rationale for combining drugs to minimize residual disease
At the American Society of Hematology Meeting in December 2019, Dr. Y. Lynn Wang gave an overview of her team’s chronic lymphocytic leukaemia proliferation model, which has demonstrated the benefits of combining ibrutinib and venetoclax. Video from ASH 2019 (December 8, 2019. 5:11)
Signaling pathways and molecular-targeted therapies in CLL and non-Hodgkin lymphoma
- B-cell receptor signaling in non-Hodgkin lymphoma and CLL
- Mechanisms of sensitivity and resistance to B-cell receptor-targeted therapies
- Molecular mechanisms of ibrutinib resistance in CLL and mantle cell lymphoma
Lab Overview
As a physician-scientist, Dr. Wang is the principal investigator of several translational research projects on aberrant signal transduction pathways in B-cell lymphoma and leukemia. Wang lab is one of the pioneering groups who explored the idea of targeting B-cell receptor (BCR) signaling in lymphoid malignancies before BCR-directed therapies became well-known and successful. The lab has shown that targeting specific components of the pathway blocked BCR signaling and generated anti-lymphoma effects. Detailed analyses of the downstream signaling cascades have enabled potential biomarker identification for therapeutic response prediction.
Interest of Wang Lab in BCR and BCR-targeted therapies has extended to the characterization of the molecular mechanisms underlying drug sensitivity and resistance. In particular, the lab contributed significantly to the understanding of the mechanisms leading to primary and secondary resistance to SYK and BTK inhibition. In May 2014, the lab reported the first discovery of BTKC481S mutation that confers ibrutinib (a BTK inhibitor) resistance in the NEJM. This has been followed by a series of studies elucidating the molecular mechanisms of primary and secondary resistance to ibrutinib in chronic lymphocytic leukemia and mantle cell lymphoma. The lab has also developed strategies for overcoming such resistance based on molecular rationales, such as using HSP90 inhibitors to overcome MYC activation in MCL. Many of the Wang lab projects involve collaborations with cytogenecists, structural biologists, hematopathologists, and heme/onc physicians.
Wang Lab has contributed ~70 papers to peer-reviewed medical and scientific literature. These include reports published in journals such as NEJM, Leukemia, JAMA Oncology, British Journal of Haematology, Oncogene, Blood and Blood Advances. Publications from Wang lab are read often with an annual citation of >250 each year since 2015 and their lymphoma research was highlighted and streamed online by OncoTV. Their article entitled “Functional characterization of BTKC481S mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors” is ranked as one of most highly cited papers published in Leukemia since 2015.
Lab Staff
Additional Staff
Wenjun Wu, PhD, postdoctoral fellow
Vicky Wang, MD, PhD, visiting scholar
Ji Ma, MD, PhD, visiting scholar
Publications
Selected Publications
Lee J, Zhang LL, Wu W, Guo H, Li Y, Sukhanova M, Venkataraman G, Huang S, Zhang H, Alikhan M, Lu P, Guo A, Galanina N, Andrade J, Wang ML, Wang YL. Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma. Blood Adv; 2(16):2039-2051. 2018 PubMed
Ming M, Wu W, Xie B, Sukhanova M, Wang W, Kadri S, Sharma S, Lee J, Shacham S, Landesman Y, Maltsev N, Lu P, Wang YL. XPO1 Inhibitor Selinexor Overcomes Intrinsic Ibrutinib Resistance in Mantle Cell Lymphoma via Nuclear Retention of IκB. Mol Cancer Ther; 17(12):2564-2574. 2018 PubMed
Wang YL. MYD88 mutations and sensitivity to ibrutinib therapy. PMID:29482770. J Mol Diagn. 20:264-266, 2018 PubMed
Guo A, Lu P, Coffey G, Conley P, Pandey A, and Wang YL. Dual SYK/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: Cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment. Ongotarget, 8:12953-12967, 2017. PubMed
Guo A, Lu P, Lee J, Zhen CJ, Chiosis G, Wang YL. HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment. Oncogene 36:3441-9, 2017 PubMed
Kadri S, Lee J, Fitzpatrick C, Galanina N, Sukhanova M, Venkataraman G, Sharma S, Long B, Petras K, Theissen M, Ming M, Kobzev Y, Kang W, Guo A, Wang W, Niu N, Weiner H, Thirman M, Stock W, Smith SM, Nabhan, C, Segal JP, Lu P and Wang YL. Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL. Blood Advances 1:715-727, 2017 PubMed
Guo A, Lu P, Galanina N, Nabhan C, Smith SM, Coleman M, and Wang YL. Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib. PMID: 26717038. Oncotarget. 7: 4598-610, 2016 PubMed
Sharma S, Galanina N, Guo A, Lee J, Kadri S, Van Slambrouck C, Long B, Ming M, Furtado LV, Segal, JP, Stock W, Venkataraman G, Tang W-J, Lu P, and Wang YL. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. PMID: 27626698. Oncotarget.7:68833-41, 2016 PubMed
Cheng S, Guo A, Lu P, Ma J, Coleman M, and Wang YL. Functional Characterization of BTKC481S mutation that confers ibrutinib resistance: Exploration of alternative kinase inhibitors. PMID: 25189416. Leukemia. 29:895-900, 2015. Ranked as one of most highly cited papers published in Leukemia from 2015 in December 2017. PubMed
Zhang SQ, Smith SM, Zhang SY, and Wang YL. Mechanisms of ibrutinib resistance in chronic lymphocytic leukemia and non-Hodgkin lymphoma. PMID: 25858358. Br J Haematol. 170:445-56, 2015 PubMed
Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, Raca G, Pandey A, Conley P, Yu H and Wang YL. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. PMID: 26575169. Oncotarget. 6: 43881-96, 2015. PubMed
Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M, Liu M, Buggy JJ, Furman RR, and Wang YL. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. PMID:24270740. Leukemia, 28: 649-57, 2014. PubMed
Furman RR*, Cheng S*, Lu P*, Setty M, Perez A, Guo A, Racchumi J, Xu G, Ma J, Coleman M, Buggy J, Leslie C, and Wang YL. Ibrutinib resistance in chronic lymphocytic leukemia. PMID: 24869597. N Engl J Med. 370: 2352-4. 2014 *Co-first authors. PubMed
Ma J, Lu P, Guo A, Cheng S, Zong H, Martin P, Coleman M, and Wang YL. Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells. PMID:24957109. Br J Haematol. 166:849-61, 2014. PubMed
Cheng S, Coffey G, Zhang XH, Shaknovich R, Song Z, Lu P, Pandey A, Melnick AM, Sinha U and Wang YL. SYK inhibition and response prediction in diffuse large B-cell lymphoma. Blood. 118, 6342-52, 2011. PubMed
Additional Publications
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