UTSA researcher receives $1 million CPRIT grant to decipher mechanisms of lymphoma

Soshnev's research focuses on chromatin, a polymer complex comprised of DNA and associated proteins. Chromatin plays a critical role in all cellular processes where DNA is involved, such as cell division, DNA damage repair and gene regulation. Histones are the most abundant class of chromatin proteins, and several classes of histones contribute to both structural and regulatory mechanisms in DNA.

"It is fascinating," Soshnev says, "that while your genetic code is largely unchanged in development, interpretation of this code is vastly different across cell types. For example, neurons express 'neuronal' genes, while muscle cells express 'muscle' ones. Dynamic modifications of histones in chromatin are one way to demarcate 'active' and 'repressive' neighborhoods in the chromosomes."

Soshnev continued, "This project started as an attempt to answer a fundamental question-how are chromatin compaction, gene expression, and histone modifications related to each other. However, we quickly realized that these very fundamental questions have an immediate real-world application."

Soshnev and collaborators recently demonstrated that chromosome decompaction can precipitate a chain of events leading to malignant transformation, and over a third of patients diagnosed with B-cell lymphoma carry somatic (i.e. tumor-specific) mutations in genes encoding H1 histones.

Soshnev and his team will decipher the genetic dependencies, consequences, and vulnerabilities of H1 loss in B-cell malignancy. Understanding the specific downstream effects of H1 histone loss can provide a new way to rescue the effects of these mutations.

"Our results show that H1 histones act as tumor suppressors in B-cells. H1 loss drives the stem cell programs in fully differentiated cells, in effect sending them back in time and increasing the potential to progress into cancer," Soshnev said. "However, a lot of details of how H1 mutations lead to malignancy remain unknown and are something we'd like to learn more about. Beyond H1 mutant lymphomas, our findings will be immediately relevant to an emerging class of malignancies associated with aberrant chromatin decompaction."

Soshnev earned an M.D. from St. Petersburg State University Faculty of Medicine in Russia and a Ph.D. in molecular and cellular biology from the University of Iowa. He joined UTSA as a faculty member in 2022 after completing a postdoctoral fellowship at The Rockefeller University in New York.