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About

Dr. Andrew P. Weng, MD, PhD
Senior Scientist

Education:

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):

Professional Experience (Clinical):

Expertise:

  • Hematology
  • Hematopathology
  • Leukemia
  • Lymphoma
  • Notch Signaling

Research Interest

My research focuses on signal transduction via the Notch receptor in lymphoid cells. Notch signaling plays an important role in directing lymphoid progenitors towards T cell fate, and when dysregulated leads to transformation of immature T cells and the development of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). By modulating Notch signals both in normal lymphoid development and in established human and mouse T-ALL tumors, we have been investigating molecular events responsible for cell fate determination and oncogenic transformation. Many of our findings have direct relevance to the development of rational therapies in the treatment of T-ALL.

  1. Identifying and characterizing leukemia stem cells. Cancer stem cells are defined experimentally as cellular subsets responsible for serial transplantability in animal models and give rise to both CSC and non-CSCs by asymmetric division, and serve as a model for human disease relapse which invariably occurs in the context of prior chemotherapy. Our current studies have identified two distinct genetic pathways which impact on LSC activity in murine models of T-ALL, and continuing efforts will characterize these pathways in human T-ALL xenograft models as well.
  2. Identifying and characterizing genetic events that collaborate with Notch signaling in leukemogenesis. We are performing retroviral insertional mutagenesis screens on various genetic backgrounds of Notch leukemias such as Pten and Ink4a/Arf null, as well as genetic variants involving our two identified LSC-modulating pathways.
  3. Characterization of Notch-regulated microRNAs. We have performed microRNA profiling in the context of both murine and human T-ALL cells, and identified a limited number of candidates for which we are characterizing predicted target mRNAs and functional contribution to the leukemia phenotype.
  4. Modeling of pediatric vs. adult T-ALL. While pediatric disease is largely curable, the same disease in adults leads to 60% mortality. While to some extent this difference could be attributable to more robust physiologic reserves of young patients, we have preliminary data suggesting that T-ALL generated from adult and pediatric programmed progenitors exhibit distinct biological properties which could underlie the phenotypic differences observed in patients.
  5. We are also just branching out into studies involving cancer stem cells in AML, and also survival pathways in non-Hodgkin lymphoma. The latter project takes advantage of the extensive primary lymphoma tissue bank and corresponding clinical database at the BC Cancer Agency.

Publications

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 (in press).

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 (in press).

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. View Abstract

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 2011. (Epub ahead of print). View Abstract

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. View Abstract

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, 2011. (Epub ahead of print). View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

Weng AP, & Lau A. Notch signaling in T-cell acute lymphoblastic leukemia. Future Oncol 1 (4): 511-9, 2005. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

Weng AP, & Aster JC. Multiple niches for Notch in cancer: context is everything. Curr Opin Genet Dev 14 (1): 48-54, 2004. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

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. View Abstract

Lab Members


Weng group
Postdoctoral Fellows Graduate Students Research/Summer Students
Dr. Vincenzo Giambra
 Chris Cochrane
Sam Gusscott
Christopher Jenkins
Helen (Olena) Shevchuk
Arla Yost
 Sonya Lam
Amy Ng
Weng groupWeng's curling group

Open Position

A full-time postdoctoral fellowship position is currently available in the lab, located in the newly constructed BC Cancer Research Center at 675 West 10th Avenue in the Terry Fox Laboratory Group. Utilizing molecular biology, cell culture, and animal modeling techniques, the successful applicant will study Notch signaling as it relates to leukemogenesis and normal early hematolymphoid development, with particular focus on identification and characterization of downstream target genes.

Applicants should have a recent PhD with a strong background in molecular biology. Prior experience in cancer biology and/or lymphoid development is desirable, and experience with animal models would be an asset. The successful candidate will be encouraged to apply for external funding during the first year. Salary/benefits are according to CIHR/NCIC guidelines. This position will remain open until filled. Please submit a letter of interest with CV by email to aweng@bccrc.ca.

Mailing Address:

   

Terry Fox Laboratory
BC Cancer Agency
675 West 10th Avenue,
Vancouver BC
Canada V5Z 1L3
Email:
aweng@bccrc.ca
Phone Numbers:
Tel: 604-675-8136
Fax: 604-877-0712

Terry Fox Laboratory
BC Cancer Agency
675 West 10th Avenue,
Vancouver BC
Canada V5Z 1L3

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