Infant Leukemia: We are using infant leukemia as a model to explore the contribution of multiple, deleterious, contributory germline variants to complex disease. Despite a high prevalence of translocations in the MLL1 gene, these translocations typically cannot transform in vitro models, when expressed at physiologic levels. Through extensive germline sequencing of infants and their parents, we have identified a recurrent pattern of germline variation in genes involved in regulating mesoderm and hematopoietic differentiation.
Normal and affected human iPSC models: Our computational work in infant leukemia has generated functional hypotheses suggesting moderate defects in hematopoietic differentiation. To test these hypotheses, we have established control and infant leukemia-patient iPSC lines coupled with CRISPR-mediated targeted engineering of candidate genes. Through collaboration with Chris Sturgeon, PhD, an expert in hematopoietic differentiation, we are conducting genomic and epigenomic characterization of any defects in our iPSC lines during definitive hematopoiesis.
Pediatric Cancer Predisposition: A growing area of interest in pediatric cancer etiology is predisposition to malignancy either through well known syndromes or congenital variation. We have a range of collaborative, translational research projects stemming from the outpatient clinic at St. Louis Children’s Hospital.
Error-corrected sequencing: The quantification of rare subclones in cancer samples has been limited due to the error rate of next-generation sequencing. We have developed a method for single DNA molecule indexing that enables error correction. Using droplet digital PCR, we have validated a limit of detection of 1 molecule in 10,000.
Age-specific changes in DNA methylation: Genetic variation is not the only driver of complex phenotypes. In collaboration with Agilent Technologies, we designed the first hybridization capture murine methylome array and applied this to identify discreet changes in DNA methylation of the promoters of two transcription factors as a function of aging.
Familial germ cell tumors: In collaboration with Markku Heikinheimo, MD, from Helsinki, Finland, we are exploring germline variation in Finnish pedigrees with familial germ cell tumors.
Nanopore MinIon early access program: Along with three other investigators in the CGSSB, the Druley lab was granted early access to the Nanopore MinIon sequencing devices, which promise extremely long read lengths (>5 kb).