- Assistant Professor, Department of Pathology, Committee on Cancer Biology, Institute for Genomics and Systems Biology, UCCCC
M.D., Ph.D., The University of Chicago
The University of Chicago
900 East 57th Street
Chicago, IL 60637
Lab website: https://mcnerneylab.uchicago.edu/
The goal of our research is to understand the genetic changes that occur in high-risk myeloid neoplasms, how these drive cancer growth, and how to target these aberrant programs therapeutically.
Over 50,000 people are diagnosed with a myeloid neoplasm every year in the U.S. alone. A high-risk subset of thesepatients is unresponsive to current treatments and their survival is less than a year, a rate that has remained unchanged for the last 40 years. The long-term goal of our work is to improve the outcome for these patients. To accomplish this, research in the lab focuses on understanding the underlying genetic abnormalities in high-risk myeloid neoplasms, which is essential to identify new treatment options.
The major approaches we are taking are:
- Determining the genomic abnormalities in high-risk myeloid mallignancies
- Understanding the transcriptional regulation of hematopoiesis and how it is altered in leukemia
- Deciphering the cls-regulatory logic of haploinsufficient transcriptional deregulation
- Leveraging this information to identify new therapeutic strategies for myeloid neoplasms
Using genome-wide approaches, including next-generation sequencing, we recently determined the genetic changes that occur in high-risk myeloid leukemias. We demonstrated that these leukemias have a distinct mutational profile. Half of high-risk myeloid neoplasms exhibit naploinsufficiency of the CUX1 transcription factor, a tumor suppressor gene on chromosome 7 (McNerney et al. 2013, Blood 121:869.) In addition, mutations that activate the RAS signaling pathway occur at significantly higher frequency than other AMLs (McNerney et al. 2014, British Journal of Haematology, 166:4). Both of these somatic changes likely cooperate to drive leukemogenesis. The laboratory is now leveraging this information to find new treatments for this disease. Current approaches include functional genomics (such as ChIP-seq and expression profiling), work with primary patient samples, and developing in vivo mouse models of high-risk myeloid leukemia for pre-clinical drug testing.