Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. The primary focus of our laboratory is to understand the transcription factor abnormalities as therapeutic targets in cancer/leukemia, particularly T-cell acute lymphoblastic leukemia (T-ALL). The most frequent genetic abnormality in T-ALL is the dysregulation of transcription factor genes. We previously identified the “core transcriptional regulatory circuits” controlled by the oncogenic transcription factor TAL1 in T-ALL. This work establishes that T-ALL cells possess the same general motifs of transcriptional circuitry that were identified earlier in stem cells. Our laboratory will develop a novel means to target these oncogenic mechanisms in T-ALL cells through combining cancer genomics with functional genetics and bioinformatics.