Joshua Riback, PhD

Baylor College of Medicine

Titles + affiliations

Assistant Professor
Baylor College of Medicine


Identifying protein-protein interactions required for nuclear condensates in NPM1-mutant AML


Each year in the United States, approximately 20,000 cases of acute myeloid leukemia (AML) are diagnosed with a 5-year survival below 30%. The most common mutation in AML is NPM1 (~30%), and while the prognosis varies, older patients treated with extensive chemotherapy have only 15-20% survival. NPM1 mutant proteins are historically characterized by their mislocalization out of the parts of the cell where the genetic material exists, and transcripts coding oncogenic factors are made (known as the nucleus). Many drugs for NPM1 mutant AML target this mislocalization but are often toxic. Perplexingly, NPM1 mutant is primarily required to maintain high levels of oncogenic factors in the nucleus where it has not been seen. In preliminary data, we find that mutant NPM1 is strongly enriched into specific regions or compartments called condensates using super-resolution live cell microscopy. Furthermore, we find substantial evidence suggesting that condensates are necessary for maintaining high levels of oncogenic factors required for maintaining the leukemic state. This proposal will expand upon these results to identify other factors in these nuclear condensates, how they coordinate with NPM1c and the molecular interactions needed. Altogether we believe this could provide the basis for new therapeutics for treating AML and that these insights may also provide critical basic principles for how leukemia and other cancers can occur.

Riback - 300x300 tight head shot

Leukemia Research Foundation grant
$150K awarded in 2023

Disease focus
Acute myeloid leukemia (AML)

Research focus
Cell Biology