Y. Lynn Wang, MD, PhD, FCAP

Professor
Division of Genomic and Molecular Pathology

Department of Pathology
The University of Chicago
5841 S. Maryland Ave.
MC 1089, Room N-316A
Chicago, IL 60637
Phone: 773.702.4397

Clinical Interests

  • Genomic and Molecular Pathology

Y. Lynn Wang, MD, PhD, is a professor and the founding Medical Director of the Genomic and Molecular Pathology at the University of Chicago Medical Center. The Division, founded in June 2013, is composed of four laboratories: Molecular Diagnostics Laboratory (PCR lab), Cytogenetics Laboratory, Clinical Genomics Laboratory and Translational Research Laboratory. The former two labs were pre-existing and the latter two were established 9 months after Dr. Wang's arrival, with assistance and contribution from team members, Drs. Jeremy Segal and Larissa Furtado. One of the major missions of the Division is to provide a comprehensive CLIA‐certified genetic and genomic laboratory service to enable personalized medicine.

Toward this goal, the GMP Division has built new space, new team, and equipped the labs with new instruments under the leadership of Dr. Wang.  After a 9-month building phase, all labs have entered into a production phase. Clinical Genomic Lab, led by Drs. Segal & Furtado with assistance from Dr. Sabah Kadri has launched three next-generation sequencing assays, including OncoScreen ST1.0  (mainly for solid tumors), OncoScreen ST2.0 (for cytology and small biopsies of solid tumor), OncoHeme 1.0, a 53-gene panel for hematological malignancies and Lung Fusion Panel.

Research Interests

  •  Development of new genomic and molecular tests

Research & Development in the clinical laboratories focuses on new molecular/genomic test development.  The new CLIA-certified tests that have gone live since the birth of the Division in June 2013 incude:

  • OncoScreen ST1.0, a 45-gene all-purpose cancer panel in March 2014.
  • OncoScreen ST2.0, a 50-gene all-purpose cancer panel suitable for cytology specimens & small biopsies in Oct 2014
  • OncoHeme 1.0 a 53-gene panel suitable for peripheral blood & bone marrow specimens from patients with hematologic malignancies in Dec 2014
  • International Scale reporting of BCR-ABL1 for CML monitoring in January 2014    
  • KRAS and NRAS mutation testing in March 2014
  • PML-RARA by a new and faster real time PCR method in April 2014
  • HPV genotyping for oropharyngeal cancers in June 2014
  • 1p/19q FISH panel for gliomas in November 2014
  • ALK FISH for lung carcinomas in January 2015
  • CEBPA mutation detection in March 2015
  • UroVysion for bladder cancers in June 2015
  • Lung Fusion Panel for lung cancers in November 2015

Still, new CLIA-certified molecular and genomic testing are in active development and will be offered to the medical center soon.

  • Targeting B-cell receptor signaling in lymphoid malignancies

Dr. Wang is the principal investigator of several translational research projects on aberrant signal transduction pathways in B-cell lymphoma and leukemia. The laboratory is one of the first to identify B-cell receptor signaling as a pathway to target B-cell malignancies.  Using inhibitors of LYN, SYK and BTK, the lab has demonstrated the critical role of B-cell receptor (BCR) signaling in lymphoma cell proliferation and survival in diffuse large B cell lymphoma (DLBCL), CLL and mantle cell lymphoma. Moreover, the lab investigates the mechanisms of drug response versus resistance and identifies potential biomarkers to predict therapeutic responses.

One of Wang Lab’s prior works has successfully led to the opening of a phase II clinical trial of dasatinib in lymphoma at Weill Cornell Medical College, where she worked previously. In May 2014, the lab reported their discovery of BTKC481S mutation in a CLL patient with ibrutinib (a BTK inhibitor) resistance in the NEJM . [UC News Release on Dr. Wang's work on ibrutinib resistance in CLL] that was followed by several studies elucidating the molecular mechanisms of primary and secondary resistance of ibrutinib.  Many other projects on DLBCL, CLL and mantle cell lymphoma are ongoing.  The projects involve a variety of molecular, cellular, immunological, biochemical, pharmacological and genomic techniques, providing a good opportunity for learning.  [Interview on a dual SYK/JAK inhibitor by Oncology TV at ASH 2013].  Many of these projects engage collaborations with other scientists, pathologists and heme/onc physicians at home and outside institutions as well as with industrial partners. Dr. Wang is a well accomplished investigator who has authored or co-authored ~60 original scientific publications.  She has given ~70 invited oral presentations outside her institution.

Other Interests

Extramurally, Dr. Wang was a member of the International BCR-ABL RQ-PCR Standardization Group whose 5-year work has led to the establishment of the first WHO International Genetic Reference Panel for quantification of BCR-ABL in CML monitoring.

In addition, Dr. Wang was an elected officer of the Association for Molecular Pathology (AMP). She was a member of the Expert Panel of the Molecular Oncology Reference Materials program of the Center for Disease Control and Prevention. She was part of the AMP JAK2/MPL mutation Guideline Working Group whose work led to the publication of laboratory practice guidelines. Besides AMP, Dr. Wang is a member of the College of American Pathologists, US and Canadian Academy of Pathology, American Society for Investigative Pathology and American Society of Hematology. She reviews manuscripts for many professional journals including Blood, Leukemia, and Cancer Cell

Training and Past Experience

Dr. Wang received her MD from Beijing Medical University in 1988 (conferred to a US MD degree in 2002) and her PhD from Brandeis University in 1996.  She completed her Clinical Pathology Residency, Clinical Molecular Pathology Fellowship and postdoctoral research training at the University of Pennsylvania.  She is board-certified in Clinical Pathology and Molecular Genetic Pathology.  Before joining the faculty of the University of Chicago, she directed the Molecular Hematopathology Laboratory and her lymphoma research laboratory at Weill Cornell Medical College for 11 years from 2002 to 2013.

Selected Peer-Reviewed Publications and Textbooks

1. Yang C, Lu P, Lee FY, Chadburn A, Barrientos JC, Leonard JP, Ye F,  Zhang D, Knowles DM, and Wang YL. Tyrosine kinase inhibition in diffuse large B-cell lymphoma: Molecular basis for anti-tumor activity and drug resistance of dasatinib. Leukemia. 22, 1755-66, 2008 

2. Lu P, Yang C, Guasparri I, Harrington W, Wang YL*, and Cesarman E*. Early events of B-cell receptor signalling are not essential for the proliferation and viability of AIDS-related lymphoma. Leukemia. 23, 807-10, 2009. *Co-corresponding author.

3. Jones AV, Chase A, Silver RT, Oscier D, Zoi K, Wang YL, Cario H, Pahl HL, Reiter A, Grand F, and  Cross NCP. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nature Genetics. 41, 446-9, 2009

4. Song Z, Lu P, Furman RR, Leonard JP, Martin P, Tyrell L, Lee FY, Knowles DM, Coleman M, and Wang YL.  Activity of SYK and PLCg2 predict apoptotic response of chronic lymphocytic leukemia cells to SRC tyrosine kinase inhibitor dasatinib. Clin. Cancer Res. 16, 587-99, 2010. 

5. White HE, Matejtschuk P, Rigsby P, Gabert J, Lin F, Wang YL, Branford S, Müller MC, Beaufils N, Beillard E, Colomer D, Dvorakova D, Ehrencrona H, Goh H-G, Housni HE, Jones D, Kairisto V, Kamel-Reid S, Kim D-W, Langabeer S, Ma ESK, Press RD, Romeo G, Wang L-H, Zoi K, Hughes T, Saglio G, Hochhaus A, Goldman JM, Metcalfe P, and Cross NCP. Establishment of the 1st World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA. Blood. 116(22):e111-7, 2010

6. 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

7. Zhen CJ and Wang YL. Molecular monitoring of CML: International Standardization of BCR-ABL quantification. J. Mol. Diagn. 15, 556-64, 2013.

8. Nayar U, Lu P, Goldstein RL, Vider J, Ballon G, Rodina A, Taldone T, Erdjument-Bromage H, Blasberg R, Melnick A, Cerchietti L, Chiosis G, Wang YL*, Cesarman E*. Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies. Blood 122:2837-47. 2013 *Co-corresponding authors.  

9.  Gong JZ, Cook JR, Greiner TC, Hedvat C, Hill CE, Lim MS, Longtine JA, Sabath D, Wang YL. Laboratory Practice Guidelines for Detecting and Reporting JAK2 and MPL Mutations in Myeloproliferative Neoplasms: A Report of the Association for Molecular Pathology. J. Mol. Diagn. 15:733-44, 2013.

10. 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. Leukemia, 28: 649-57, 2014.

11. 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

12. 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.

13. 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.

14. 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

15. Nabhan C, Raca G, and Wang YL. Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era. PMID: 26181643.
JAMA Oncol. doi:10.1001/jamaoncol.2015.0779 (published online May 7, 2015).

16. Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, Raca G, Pandey A, Conley P, Yu H and Wang YL. Dual SYK/JAK inhibition has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. PMID: 26575169. Oncotarget. doi: 10.18632/oncotarget.6316 (published online Nov 5, 2015).

17. 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 (Oncotarget accepted Nov 25, 2015).

 

NCI News Release

PubMed link to Dr. Y. Lynn Wang publications