MD, PhD, FRCPC
Multiple myeloma (MM) is a tumor resulting from clonal expansion of plasma cells that constitutes 10% of hematological malignancies. Survival times in MM are very heterogeneous amongst subgroups with different genetic profiles. The primary focus of my lab is to characterize the genomic aberrations responsible for initiation and progression of MM, and to identify genetic risk factors that predict clinical outcome in MM patients as well as potential molecular targets in future therapy.
In addition, as preclinical studies, we investigate small molecule inhibitors that disrupt p53-MDM2 interactions and induce apoptosis in myeloma cells. We also evaluate novel small molecules that can change the conformation of a mutant p53 to a functional wild-type p53 to restore p53 functions as a novel therapeutic strategy, particularly in those high-risk MM patients harboring p53 deletions/mutations.
Yang Y, Li F, Saha MN, Abdi J, Qiu Liu, Chang H. miR-137/197 induce apoptosis and suppress tumorigenicity by targeting MCL-1 in multiple myeloma. Clin Cancer Res. 2015 Feb 27. doi:10.1158/1078-0432. (SRA)
Yang Y, Chen Y, Saha MN, Chen J, Evans K, Qiu L, Reece D, An Chen G, Chang H. Targeting phospho-MARCKS overcomes drug resistance and induces antitumor activity in preclinical models of multiple myeloma. Leukemia. 2015 Mar;29(3):715-26. (SRA)
Mona Sobhani, MN Saha, Abdi J, Chen C, Chang H. PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53. Cancer Biol Ther. 2015 Mar 24:0. [Epub ahead of print]
Jiang N, Qi XY, Chang H. Dutcher bodies in multiple myeloma are highly associated with translocation t(4;14) and isotype IgA. Br J Haematol. 24 APR 2015 | DOI: 10.1111/bjh.13457 (SRA)
Saha MN, Chen Y, Chen MH, Chen G, Chang H. Small molecule MIRA-1 induces in vitro and in vivo anti-myeloma activity and synergizes with current anti-myeloma agents. Br J Cancer. 2014 Apr 29;110(9):2224-31. (SRA)
Abdi J, Qiu LQ, Chang H. Micro-RNAs, New Performers in Multiple Myeloma Bone Marrow Microenvironment. Biomark Res. 2014 May 30;2:10 (SRA)
Abdi J, Chen G, Chang H. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget. 2013 Dec;4(12):2186-207. (SRA)
Saha M, Y Yang, D Reece, Chang H. PRIMA-1Met/APR-246 displays high anti-tumor activity in multiple myeloma by induction of p73 and Noxa. Molecular Cancer Therapeutics, 2013 Nov;12(11):2331-41. (SRA)
Bahmanyar M, Qi XY , Chang H. Genomic aberraions in anaplastic myeloma: high frequency of 1q21(CKS1B) amplifications. Leuk Res. 2013 Dec;37(12):1726-8. (SRA).
Saha M, Qiu L, Chang H. Targeting p53 by small molecules in hematological malignancies. J Hematol Oncol. 2013 Mar 27;6:23. (SRA)
Jiang H, Saha MN, Muaki A, Chang H. RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses. Mol Cancer Ther 2010,9:3041–51. (SRA)
Chen M, Qi C, Trieu Y, Reece D, Chang H. Aberrant p53 expression correlates with hemizygous p53 deletion and has an adverse impact on the outcome of refractory/relapsed multiple myeloma patients treated with lenalidomide. Am J Clin Pathol. 2012;137:208-12. (SRA)
Jiang N, Qi C, Trieu Y, Reece D, Chang H. Genomic aberrations and survival in light chain only multiple myeloma. Bio Blood Marrow Transplant. 17:1790-5. 2011. (SRA)
Jiang A, Reece D, Chang H. Impact of molecular cytogenetic aberrations in multiple myeloma in the era of novel therapeutic agents. Leuk Lymphoma, 2012 Feb;53(2):202-7. (SRA)
Saha MN, Mukai A, Qi C, Reece D, Chang H. Molecular mechanisms mediating antimyeloma activity of an MDM2 antagonist nutlin: Evidence for a p53 transcription dependent and independent pathway. Cancer Biology &Therapy; 10(6):567-78. 2010 (SRA)
Micallef J, Dharsee M, Chen J, Ackloo S, Qiu L, Chang H. Application of proteomics in the study of multiple myeloma. J Hematol & Oncol. 2010 Apr 7;3:13. Review. (SRA)
Chang H, Jiang N, Jiang H, Saha MN, Qi C, Xu W, Reece D. CKS1B nuclear expression is inversely correlated with 27Kip1 expression and is predictive of an adverse survival in multiple myeloma. Haematologica, 2010, 95(9):1542-7. (SRA)
Staff Physician, Department of Laboratory Hematology, Hematology and Oncology, Princess Margaret Cancer Center/Toronto General Hospital