Dr. Malek was an early advocate of use of SNP arrays to interrogate cancer genomes and he and his team developed software tools and experimental guidelines to interpret result with high sensitivity and specificity. The resulting findings have furthered our understanding of the pathological genomic anatomy of CLL, AML and FL. The findings of SNP array-based genomic complexity as an independent biomarker for short survival and the strong associations with TP53 mutations are noteworthy examples of their work, as are improved recognitions of the biological principles or gene aberrations underlying major genomic deletion types in CLL, FL or AML. He made contributions to targeted therapy development as exemplified by pre-clinical work on MDM2 inhibitors in CLL or AML and the discovery of activating STAT6 mutations as part of the IL4/JAK/STAT6 axis in FL. Ongoing work centers on basic to translational research questions and increasingly focus on drug targets as well as the biological changes that characterize relapsed hematological neoplasms.
Work in the lab currently is directed at i) genomic characterization of CLL including clonal evolution after therapy and understanding the underlying biology of recurrent genomic aberrations and mutations, ii) targeted therapy development in CLL, iii) genomic characterization of AML cells including research on chemotherapy refractoriness and genomic MRD and its cellular sources, and, iv) ongoing genomic characterization of follicular lymphoma including work on the IL4/JAK/STAT6 axis and novel recurrently mutated genes in the amino acid signaling to mTOR axis. Overall goals are improvements in prognosis and therapy in hematological neoplasms.