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Yue Lynn Wang, MD, PhD, FCAP

Yue Lynn Wang, MD, PhD, FCAP

Clinical Locations

Primary Location

Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111

About

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 >16 years of experience with many contributions to the medical literature.  She served as the Founding Director of the Genomic and Molecular Pathology Division at the University of Chicago.

BTKC481S disrupts the covalent binding of ibrutinib to BTK
BTKC481S mutation restores the activity of the BCR signaling pathway
Novel ibrutinib-resistant BTKT316A mutation identified
Evolutionary dynamics of the major ibrutinib-resistant clones during disease relapse
Activation of MYC contributes to intrinsic ibrutinib resistance in mantle cell lymphoma

Twitter: @DrLynnWang

Education and Training

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 Program

Research Interests

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.


Wang Lab was recently opened at Fox Chase Cancer Center in October 2018 after relocating from the University of Chicago.  The lab is currently recruiting a technician with 3-5 years of bench experience in biomedical sciences.

BTKC481S disrupts the covalent binding of ibrutinib to BTK
BTKC481S mutation restores the activity of the BCR signaling pathway
Novel ibrutinib-resistant BTKT316A mutation identified
Evolutionary dynamics of the major ibrutinib-resistant clones during disease relapse
Activation of MYC contributes to intrinsic ibrutinib resistance in mantle cell lymphoma
Lab Staff

Pin Lu, MD, PhD

Research Assistant Professor

Room: W328
215-728-8389

Additional Staff

Wang Lab was recently opened at Fox Chase Cancer Center in October 2018 after relocating from the University of Chicago.  The lab is currently recruiting a technician with 3-5 years of bench experience in biomedical sciences.

Publications

Selected Publications

Ming M, Wu W, Xie B, Sukhanova M, Wang W, Kadri S, Sharma S, Lee J, Shacham S, Landesman Y, Maltsev N, Lu P, and Wang YL. XPO1 inhibition antagonizes MCL via nuclear retention of IkB: Selinexor demonstrates antitumor activities in both ibr-sensitive and ibr-resistant tumor cells. Mol Cancer Ther (in print).

Wang YL.  MYD88 mutations and sensitivity to ibrutinib therapy. PMID:29482770. J Mol Diagn. 20:264-266, 2018
Lee J, Zhang LL, Wu W, Guo H, Li Y, Sukhanova M, Venkataraman G, Zhang H, Alikhan M, Lu P, Guo A, Galanina N, Andrade J, Wang ML and Wang YL.  Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma. Blood Adv. 2:2039-2051, 2018

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.

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
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

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
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

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.
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
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.

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.
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.

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.

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.

Additional Publications

MyNCBI

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