Academic Rank:
Professor, UBC
Senior Scientist, Terry Fox Laboratory
Affiliation(s):
Short Bio:

Weng Lab

Dr. Andrew Weng attended Stanford University for his undergraduate studies in Biological Sciences and then obtained his MD and PhD degrees at the University of Chicago/Pritzker School of Medicine. He did his clinical residency training in Anatomic Pathology with a fellowship in hematopathology, followed by four years of postdoctoral research training at Brigham & Women’s Hospital in Boston. In 2004, he was recruited as an Assistant Professor in the Department of Pathology and Laboratory Medicine, University of British Columbia (UBC) and started his own research lab at BC Cancer Agency (BCCA). He was promoted to Associate Professor in 2011, and then full Professor in 2018. Dr. Weng is also a staff hematopathologist, Director of both the clinical flow cytometry and research core flow cytometry labs, as well as Medical Director of the Stem Cell Assay lab. Dr. Weng’s research program focuses on the pathogenetic mechanisms in acute lymphoblastic leukemia and tumor heterogeneity in B-cell lymphoma. He is currently funded by 2 CIHR project grants and 2 TFRI program project grants.

Academic background

  • MD (Pritzker School of Medicine), University of Chicago, 1997
  • PhD (Molecular Genetics and Cell Biology), University of Chicago, 1995
  • BS (Biological Sciences), Stanford University, 1989

Post-Graduate Training:

  • Postdoctoral Research Fellow in Pathology (Supervisor: Dr. Jon Aster)
    Brigham & Women’s Hospital/Harvard Medical School
    July 2000 – May 2004
  • Clinical Fellow in Hematopathology
    Brigham & Women’s Hospital/Harvard Medical School
    July 1999 – June 2000
  • Resident in Anatomic Pathology
    Brigham & Women’s Hospital/Harvard Medical School
    July 1997 – June 1999

Professional Experience (Research):

  • Distinguished Scientist, Terry Fox Laboratory, BC Cancer Agency (BCCA), 2018-present
  • Professor, Pathology & Laboratory Medicine, University of British Columbia (UBC), 2018-present
  • Scientific Director, Flow Core Laboratory, BCCA, 2014-present
  • Associate Professor, Pathology & Laboratory Medicine, UBC, 2011-2018
  • Senior Scientist, Terry Fox Laboratory, BCCA, 2005-2018
  • Medical Director, Stem Cell Assay Laboratory, BCCA, 2012-present
  • Assistant Professor, Pathology & Laboratory Medicine, UBC, 2004-2011
  • Clinician Scientist, Department of Pathology, BCCA, 2004-present
  • Instructor, Department of Pathology, Harvard Medical School, 2001-2006

Professional Experience (Clinical):

  • Consulting Staff, Department of Pathology, Hematopathology Division, Vancouver General Hospital (VGH), 2016-present
  • Director, Hematopathology, BCCA, 2006-2011
  • Director, Clinical Flow Cytometry Lab, BCCA, 2005-present
  • Hematopathologist, BCCA, 2004-present
  • Hematopathologist, Dana Farber Cancer Institute, 2001-2004
  • Associate Pathologist, Brigham & Women’s Hospital, 2001-2004

Publications

  1. Gusscott S, Jenkins CE, Lam SH, Giambra V, Pollak M, Weng AP. IGF1R derived PI3K/AKT signaling maintains growth in a subset of human T-cell acute lymphoblastic leukemias. PLoS One. 11(8):e0161158, 2016.
  2. Parker JDK, Shen Y, Pleasance E, Li Y, Schein JE, Zhao Y, Moore R, Wegrzyn-Woltosz J, Savage KJ,Weng AP, Gascoyne RD, Jones S, Marra M, Laskin J, Karsan A. Molecular etiology of an indolent lymphoproliferative disorder determined by whole-genome sequencing. Cold Spring Harb Mol Case Stud 2: a000679, 2016.
  3. Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, FirestoneGarnache B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekoffer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM , Kung AL, Kupper TS, LaBoeuf N, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell 29(4):574-86, 2016.
  4. Hoofd C, Wang X, Lam S, Jenkins C, Wood B, Giambra V*, Weng AP*.  CD44 promotes chemoresistance in T-ALL by increased drug efflux.  Exp Hematol. 44(3):166-171, 2016 (*equal contribution)
  5. Giambra V, Jenkins C, Lam SH, Hoofd C, Belmonte M, Wang X, Gusscott S, Gracias D & Weng AP.
    Leukemia stem cells in T-ALL require active Hif1α and Wnt signaling. Blood 125:3917-27, 2015.
  6. Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, Jenkins CE, Hannett NM, McMillin D, Sanda T, Sim T, Kim ND, Look T, Mitsiades CS, Weng AP, Brown JR, Benes CH, Marto JA, Young RA, Gray NS. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature 511: 616-620, 2014.
  7. Gutierrez A, Pan L, Groen RWJ, Baleydier F, Kentsis A, Marineau J, Grebliunaite R, Kozakewich E, Reed C, Pflumio F, Poglio S, Uzan B, Clemons P, VerPlank L, An F, Burbank J, Norton S, Tolliday N, Steen H, Weng AP, Yuan H, Bradner JE, Mitsiades C, Look AT & Aster JC. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. The Journal of Clinical Investigation 124: 644-655, 2014. View Abstract
  8. Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, Yost A, Ma W, Fleischman AG, Zhou W, Yang Y, Kleppe M, Ahn Y, ., Tatarek J, Kelliher M, Neuberg D, Levine RL, Moriggl R, Muller M, Gray NS, Jamieson CH, Weng AP, Staudt LM, Druker BJ & Look T. TYK2-STAT1-BCL2 pathway dependence in T-Cell Acute Lymphoblastic Leukemia.  Cancer Discov 3: 564-577, 2013.
  9. Aghaeepour N, Finak G, the FlowCAP Consortium, the DREAM Consortium, Hoos H, Mosmann TR, Gottardo R, Brinkman RR & Scheuermann RH. Critical assessment of automated flow cytometry data analysis techniques. Nature Methods 10: 228-38, 2013 (Weng AP is a member of the FlowCAP Consortium).
  10. Yost AJ, Shevchuk OO, Gooch R, Gusscott S, You MJ, Ince TA*, Aster JC* & Weng AP*. Defined, serum-free conditions for in vitro culture of primary human T-ALL blasts. Leukemia 6: 1437-40, 2012 (* equal contribution).
  11. Giambra V, Jenkins CR, Wang H, Lam SH, Shevchuk OO, Nemirovsky O, Wai C, Gusscott S, Chiang MY, Aster JC, Humphries RK, Eaves C & Weng AP. NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-q and reactive oxygen species.  Nat Med 18: 1693-8, 2012. (featured on the cover of the Nov 2012 issue)
  12. Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Holzenberger M, Pollak M, Humphries RK & Weng AP. IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein. Exp Hematol 40:715-723, 2012.
  13. Gusscott S, Kuchenbauer F, Humphries RK & Weng AP. Notch-mediated repression of miR-223 contributes to IGF1R regulation in T-ALL. Leuk Res 36:905-11, 2012.
  14. Bashashati A, Johnson NA, Khodabakhshi AH, Whiteside MD, Zare H, Scott DW, Lo K, Gottardo R, Brinkman FSL, Connors JM, Slack GW, Gascoyne RD, Weng AP* & Brinkman RR* (*co-senior authors). B-cells with high side scatter parameter by flow cytometry correlate with inferior survival in diffuse large B cell lymphoma. Am J Clin Pathol 137: 805-814, 2012.
  15. Kridel R, Messner B, Rogic S, Boyle M, Telenius A, Woolcock B, Gunawardana J, Jenkins C, Cochrane C, Ben-Neriah S, Tan K, Opat S, Sehn LJ, Connors JM, Weng AP*, Steidl C* & Gascoyne RD* (*co-senior authors). Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood 119: 1963-1971, 2012.
  16. Zare H, Bashashati A, Kridel R, Aghaeepour N, Haffari G, Connors HM, Gupta A, Gascoyne RD, Brinkman RR* & Weng AP* (*co-senior authors). Automated analysis of multidimensional flow cytometry data improves diagnostic accuracy between mantle cell lymphoma and small lymphocytic lymphoma. Am J Clin Pathol 137:75-85, 2012.
  17. Dakappagari N, Ho SN, Gascoyne RD, Ranuio J, Weng AP*, Tangri S* (*co-senior authors). CD80 (B7.1) is expressed on both malignant B cells and non-malignant stromal cells in non-Hodgkin lymphoma. Cytometry B Clin Cytom 82: 112-119, 2012.
  18. Maddigan A, Truitt L, Arsenault R, Freywald T, Allonby O, Dean J, Narendran A, Xiang J, Weng A, Napper S, Freywald A. EphB receptors trigger Akt activation and suppress Fas receptor-incuced apoptosis in malignant T lymphocytes. J Immunol 187:5983-5994, 2011.
  19. Habibi D, Ogloff N, Jalili RB, Yost A, Weng AP, Ghahary A & Ong CJ. Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia.  Invest New Drugs 30:1361-70, 2011.
  20. Medyouf H, Gusscott S, Wang H, Tseng JC, Wai C, Nemirovsky O, Trumpp A, Pflumio F, Carboni J, Gottardis M, Pollak M, Kung AL, Aster JC, Holzenberger M, Weng AP. High level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling. J Exp Med 208: 1809-1822, 2011. (featured on the cover of Nov 2011 issue)
  21. Finak G, Perez J-M, Weng A & Gottardo R. Optimizing transformations for automated, high throughput analysis of flow cytometry data. BMC Bioinformatics 11: 546, 2010.
  22. Petriv OI, Kuchenbauer F, Delaney AD, Lecault V, White A, Kent D, Marmolejo L, Heuser M, Berg T, Copley M, Ruschmann J, Sekulovic S, Benz C, Kuroda E, Ho V, Antignano F, Halim T, Giambra V, Krystal G, Takei F, Weng AP, Piret J, Eaves C, Marra MA, Humphries RK & Hansen CL. Comprehensive microRNA expression profiling of the hematopoietic hierarchy. Proc Natl Acad Sci USA 107:15443-8, 2010.
  23. Medyouf H, Gao XH, Armstrong F, Gusscott S, Liu Q, Gedman AL, Matherly LH, Schultz KR, Pflumio F, You MJ & Weng AP. Acute T-cell leukemias remain dependent on notch signaling despite PTEN and INK4A/ARF loss.  Blood 115:1175-84, 2010.
  24. Hahne F*, Khodabakhshi AH*, Bashashati A, Wong C-J, Gascoyne RD, Weng AP, Seifert-Margolis S, Bourcier K, Asare A, Lumley T, Gentleman R & Brinkman RR. Per-channel basis normalization methods for flow cytometry data.  Cytometry A 77: 121-31, 2010.
  25. Heuser M, Sly LM, Argiropoulos B, Kuchenbauer F, Lai C, Weng A, Leung M, Lin G, Brookes C, Fung S, Valk PJ, Delvel R, Lowenberg B, Krystal G & Humphries RK. Modeling the functional heterogeneity of leukemia stem cells: Role of STAT5 in leukemia stem cell self-renewal. Blood, 114:3983-3993, 2009. View Abstract
  26. Johnson NA, Boyle M, Bashashati A, Leach S, Brooks-Wilson A, Sehn LH, Chhanabhai M, Brinkman RR, Connors JM, Weng AP & Gascoyne RD. Diffuse large B cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood 113: 3773-80, 2009.
  27. Chan SM, Weng AP, Tibshirani R, Aster JC, & Utz PJ. Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia. Blood 110 (1): 278-86, 2007.
  28. Rodig SJ, Savage KJ, LaCasce AS, Weng AP, Harris NL, Shipp MA, Hsi ED, Gascoyne RD, & Kutok JL. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol 31 (1): 106-12, 2007.
  29. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, Barnes KC, O’Neil J, Neuberg D,Weng AP, Aster JC, Sigaux F, Soulier J, Look AT, Young RA, Califano A, & Ferrando AA. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A 103 (48): 18261-6, 2006.
  30. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C, Del Bianco C, Rodriguez CG, Sai H, Tobias J, Li Y, Wolfe MS, Shachaf C, Felsher D, Blacklow SC, Pear WS, & Aster JC. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 20 (15): 2096-109, 2006.
  31. Ringrose A, Zhou Y, Pang E, Zhou L, Lin AE, Sheng G, Li XJ, Weng A, Su MW, Pittelkow MR, & Jiang X. Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas. Leukemia 20 (9): 1593-601, 2006.
  32. Weng AP, & Lau A. Notch signaling in T-cell acute lymphoblastic leukemia. Future Oncol 1 (4): 511-9, 2005.
  33. Sanchez-Irizarry C, Carpenter AC, Weng AP, Pear WS, Aster JC, & Blacklow SC. Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeats. Mol Cell Biol 24 (21): 9265-73, 2004.
  34. Weng AP, Ferrando AA, Lee W, Morris JPt, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, & Aster JC. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306 (5694): 269-71, 2004.
  35. Maillard I, Weng AP, Carpenter AC, Rodriguez CG, Sai H, Xu L, Allman D, Aster JC, & Pear WS. Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 104 (6): 1696-702, 2004.
  36. Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, & Shipp M. Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma 45 (4): 761-7, 2004.
  37. Brown JR, Weng AP, & Freedman AS. Hodgkin disease associated with T-cell non-Hodgkin lymphomas: case reports and review of the literature. Am J Clin Pathol 121 (5): 701-8, 2004.
  38. Das I, Craig C, Funahashi Y, Jung KM, Kim TW, Byers R, Weng AP, Kutok JL, Aster JC, & Kitajewski J. Notch oncoproteins depend on gamma-secretase/presenilin activity for processing and function. J Biol Chem 279 (29): 30771-80, 2004.
  39. Weng AP, & Aster JC. Multiple niches for Notch in cancer: context is everything. Curr Opin Genet Dev 14 (1): 48-54, 2004.
  40. Weng AP, & Aster JC. No T without D3: a critical role for cyclin D3 in normal and malignant precursor T cells. Cancer Cell 4 (6): 417-8, 2003.
  41. Dorfman DM, van den Elzen P, Weng AP, Shahsafaei A, & Glimcher LH. Differential expression of T-bet, a T-box transcription factor required for Th1 T-cell development, in peripheral T-cell lymphomas. Am J Clin Pathol 120 (6): 866-73, 2003.
  42. Weng AP, Shahsafaei A, & Dorfman DM. CXCR4/CD184 immunoreactivity in T-cell non-Hodgkin lymphomas with an overall Th1- Th2+ immunophenotype. Am J Clin Pathol 119 (3): 424-30, 2003.
  43. Nam Y, Weng AP, Aster JC, & Blacklow SC. Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex. J Biol Chem 278 (23): 21232-9, 2003.
  44. Weng AP, Nam Y, Wolfe MS, Pear WS, Griffin JD, Blacklow SC, & Aster JC. Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol 23 (2): 655-64, 2003.
  45. Wohlschlegel JA, Kutok JL, Weng AP, & Dutta A. Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol 161 (1): 267-73, 2002.
  46. Gaudet G, Friedberg JW, Weng A, Pinkus GS, & Freedman AS. Breast lymphoma associated with breast implants: two case-reports and a review of the literature. Leuk Lymphoma 43 (1): 115-9, 2002.
  47. Izon DJ, Aster JC, He Y, Weng A, Karnell FG, Patriub V, Xu L, Bakkour S, Rodriguez C, Allman D, & Pear WS. Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1. Immunity 16 (2): 231-43, 2002.
  48. Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL, Aguiar RC, Gaasenbeek M, Angelo M, Reich M, Pinkus GS, Ray TS, Koval MA, Last KW, Norton A, Lister TA, Mesirov J, Neuberg DS, Lander ES, Aster JC, & Golub TR. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 8 (1): 68-74, 2002.
  49. Weng A, Magnuson T, & Storb U. Strain-specific transgene methylation occurs early in mouse development and can be recapitulated in embryonic stem cells. Development 121 (9): 2853-9, 1995.
  50.  Weng A, Engler P, & Storb U. The bulk chromatin structure of a murine transgene does not vary with its transcriptional or DNA methylation status. Mol Cell Biol 15 (1): 572-9, 1995.
  51. Engler P, Weng A, & Storb U. Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate. Mol Cell Biol 13 (1): 571-7, 1993.
  52. Storb U, Engler P, Klotz E, Weng A, Haasch D, Pinkert C, Doglio L, Glymour M, & Brinster R. Rearrangement and expression of immunoglobulin genes in transgenic mice. Curr Top Microbiol Immunol 182: 137-41, 1992.
  53. Chensue SW, Shmyr-Forsch C, Weng A, Otterness IG, & Kunkel SL. Biologic and immunohistochemical analysis of macrophage interleukin- 1 alpha, – 1 beta, and tumor necrosis factor production during the peritoneal exudative response. J Leukoc Biol 46 (6): 529-37, 1989.
Primary Research Area
Cancer
Secondary Research Area
Blood research

Research Interest

Expertise:

  • Hematology
  • Hematopathology
  • Leukemia
  • Lymphoma
  • Notch Signaling

 

My research program focuses on the pathogenesis of lymphoid malignancy and entails two major arms. First, we have explored the role of NOTCH1 and other oncogenes/tumor suppressors in the genesis and propagation of T-cell acute lymphoblastic leukemia (T-ALL) including studies on downstream target genes/pathways and identifying mechanisms operative in leukemia stem cells. We have addressed these questions in cells from different developmental stages and tissue contexts on the hypothesis that preset epigenetic programs may restrict the oncogenic trajectories available to the cells as they undergo the initial stages of transformation and clonal establishment. Many of our findings have direct clinical relevance in that they serve as basis for the development of rational therapies that target disease-specific phenotypes.

As a second and more recent focus, my lab has explored the use of state-of-the-art mass cytometry (CyTOF) to obtain highly resolved phenotypic maps of heterogeneous cell populations in present in patient lymphoma biopsy samples including both malignant and reactive immune cell compartments. We have used this methodology to characterize intratumoral heterogeneity/subclonal diversity among malignant cell populations and stereotyped or patient-specific immune responses. This work is also of direct clinical relevance in providing detailed phenotypic characterizations that are required in order to define biomarkers for lymphoma classification and prognosis, and monitoring of patient-specific responses to therapy.

Currently Established Methodologies and Approaches

  • Synthetic human models of leukemia/lymphoma
  • Conventional mouse models of leukemia/lymphoma
  • Patient-derived xenograft (PDX) models of leukemia
  • Access to clinically annotated primary human lymphoma specimens
  • Lentiviral gene transduction, CRISPR/Cas9 gene editing
  • RNA-seq, ChIP-seq, single cell RNA-seq, whole exome seq
  • High parameter flow cytometry (BD FACSymphony), mass cytometry (CyTOF)

Access to primary human lymphoma specimens

Dr. Weng is the Director of the BCCA Clinical Flow Cytometry Lab and co-manages the Lymphoma Tumor Repository with Drs. Christian Steidl and David Scott. The clinical flow lab accessions nearly 4,000 specimens each year for assessment of lymphoproliferative disease (LPD) including representative portions of ~1,000 excisional lymph node (LN) biopsies. Among these, approximately 100 per year represent follicular lymphoma (FL) and another 100 per year represent diffuse large B cell lymphoma (DLBCL). Single cell suspensions are generated by manual disaggregation and processed for flow cytometric phenotyping using our routine 13-color clinical assay (BD LSRFortessa platform). After diagnostic testing is completed, there are often several to tens of millions of excess viable cells remaining which are prospectively banked with DMSO cryoprotectant. This has been going on for over 2 decades as part of the well established BCCA Lymphoma Program. There are currently over 1,300 cases each of FL and DLBCL in the tumor bank, as well as abundant reactive (normal) lymph nodes to serve as a source of normal control material.

Current projects in my lab include:

Open Positions:

The Weng lab currently has open positions available at the Postdoctoral or Graduate student level working on pathogenetic mechanisms in T-ALL and/or analysis of tumor ecosystem in human lymphoma by mass cytometry (CyTOF).  Interested applicants may submit letter of interest and CV to aweng@bccrc.ca.