BHATIA PROGRAM
McMaster University
PUBLICATIONS
2023
Diana Golubeva, Deanna P Porras, Meaghan Doyle, Jennifer C Reid, Borko Tanasijevic, Allison L Boyd, Kinga Vojnits, Amro Elrafie, Amy Qiao, Mickie Bhatia https://doi.org/10.1093/stcltm/szad022
Screening of primary patient acute myeloid leukemia (AML) cells is challenging based on intrinsic characteristics of human AML disease and patient-specific conditions required to sustain AML cells in culture. This is further complicated by inter- and intra-patient heterogeneity, and “contaminating” normal cells devoid of molecular AML mutations. Derivation of induced pluripotent stem cells (iPSCs) from human somatic cells has provided approaches for the development of patient-specific models of disease biology and has recently included AML. Although reprogramming patient-derived cancer cells to pluripotency allows for aspects of disease modeling, the major limitation preventing applications and deeper insights using AML-iPSCs is the rarity of success and limited subtypes of AML disease that can be captured by reprogramming to date. Here, we tested and refined methods including de novo, xenografting, naïve versus prime states and prospective isolation for reprogramming AML cells using a total of 22 AML patient samples representing the wide variety of cytogenetic abnormalities. These efforts allowed us to derive genetically matched healthy control (isogenic) lines and capture clones found originally in patients with AML. Using fluorescently activated cell sorting, we revealed that AML reprogramming is linked to the differentiation state of diseased tissue, where use of myeloid marker CD33 compared to the stem cell marker, CD34, reduces reprogramming capture of AML+ clones. Our efforts provide a platform for further optimization of AML-iPSC generation, and a unique library of iPSC derived from patients with AML for detailed cellular and molecular study.
Cell, 2012
IDENTIFICATION OF DRUGS INCLUDING A DOPAMINE RECEPTOR ANTAGONIST THAT SELECTIVELY TARGET CANCER STEM CELLS
Sachlos E, Risueno R, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli AO, Hassell JA, Fischer- Russell D, Trus MR, Foley R, Leber B, Xenocostas A, Browne ED, Collins T, and Bhatia M
Nature Cell Biology, 2017
ACUTE MYELOID LEUKEMIA DISRUPTS ENDOGENOUS MYELO-ERYTHROPOIESIS BY COMPROMISING THE ADIPOCYTE BONE MARROW NICHE
Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, Nakanishi M, Porras DP, Almakadi M, Campbell CJV, Jackson MF, Ross CA, Foley R, Leber B, Allan DS, Sabloff M, Xenocostas A, Collins TJ, and Bhatia M
Cancer Cell 2016
GSK3 DEFICIENCIES IN HEMATOPOIETIC STEM CELLS INITIATE PRE-NEOPLASTIC STATE THAT IS PREDICTIVE OF CLINICAL OUTCOMES OF HUMAN ACUTE LEUKEMIA
Guezguez B, Almakadi M, D Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn A, Casado FL, Tanasijevic B, Bresolin S, Masetti R, Doble BW, Bhatia M
Cancer Cell, 2018
Allison Boyd*, Lili Aslostovar*, Jennifer Reid, Wendy Ye, Borko Tanasijevic, Deanna Porras, Zoya Shapovalova, Mohammed Almakadi, Ronan Foley, Brian Leber, Anargyros Xenocostas, Mickie Bhatia
*indicates co-lead authors
IDENTIFICATION OF CHEMOTHERAPY-INDUCED LEUKEMIC REGENERATING CELLS REVEALS A TRANSIENT VULNERABILITY OF HUMAN AML RECURRENCE
Nature Biotechnology, 2009
CHARACTERIZATION OF HUMAN EMBRYONIC STEM CELLS WITH FEATURES OF NEOPLASTIC PROGRESSION
Tamra E Werbowetski-Ogilvie, Marc Bossé, Morag Stewart, Angelique Schnerch, Veronica Ramos-Mejia, Anne Rouleau, Tracy Wynder, Mary-Jo Smith, Steve Dingwall, Tim Carter, Christopher Williams, Charles Harris, Joanna Dolling, Christopher Wynder, Doug Boreham, Mickie Bhatia
Nature, 2007
IGF AND FGF COOPERATIVELY ESTABLISH THE REGULATORY STEM CELL NICHE OF PLURIPOTENT HUMAN CELLS IN VITRO
Sean C Bendall, Morag H Stewart, Pablo Menendez, Dustin George, Kausalia Vijayaragavan, Tamra Werbowetski-Ogilvie, Veronica Ramos-Mejia, Anne Rouleau, Jiabi Yang, Marc Bossé, Gilles Lajoie, Mickie Bhatia
SELECTED PUBLICATIONS
COVER ART
Aslostovar L, Boyd AL, Benoit YD, Lu JD, Rodriguez JLG, Nakanishi M, Porras DP, Reid JC, Mitchell RR, Leber B, Xenocostas A, Foley R, and Bhatia M