Experimental Hematology and Cancer Biology
Miles Lab

Our Research

Cancer development occurs through sequential genomic, epigenomic and cellular state alterations, which converge to transform normal cells into malignant clones. While these steps can differ based on the cell of origin, tissue identity and specific somatic alterations, the ultimate result is the same — unchecked proliferation/growth, abnormal signaling/response to signals and aberrant cell identity / function.

The Miles lab is interested in understanding this processive development of cancer using acute myeloid leukemia (AML) as a model disease. AML is thought to develop through sequential mutagenic events culminating in the aberrant expansion of mutant, immature cells in lieu of mature, fully functioning blood cells. The mutational landscape of AML is well known; however, critical questions remain unanswered that we hope to help answer including:

  • How do mutations synergize on a cellular level to lead to leukemic transformation?
  • Once a mutation is acquired, how dependent are mutant cells on that mutation? Do co-occurring mutations affect this dependency?
  • Does the order of mutagenesis on a clonal level impact leukemia development?
  • How does the unique combination of mutations in a particular order lead to differential responses in an AML patient?

Research figure from the Miles Lab.

To address these questions, we use a combination of single cell multi-omic technologies in AML patient samples and complex pre-clinical mouse models of disease. The mouse models recapitulate disease phenotypes that we observe in patients and allow us to dissect cellular alterations imparted by a mutation or combination of mutations. The insights garnered from these studies have the potential to discover clone-specific therapeutic vulnerabilities. Our ultimate goal is to identify novel therapeutic strategies that create improved personalized treatments for AML patients.

About the PI

A photo of Linde Miles.

Linde A. Miles, PhD

I’m an assistant professor, scientist and researcher focused on acute myeloid leukemia, cancer evolution and cancer biology.

Learn More and Meet My Team