世界杯官方app researcher receives $1 million CPRIT grant to decipher mechanisms of 淋巴瘤

2024年4月16日 Dr. Alexey一. Soshnev, 世界杯官方app神经科学系的助理教授, 发育与再生生物学, 被判三年监禁, 一百万美元的资助 预防癌症 & 德州研究院(CPRIT) to underst和 fundamental mechanisms driving transformation 和 progression of 淋巴瘤s — the malignancies arising from peripheral B-cells, a type of white blood cell found in the bloodstream 和 lymphatic system, 和 the cause of two common cancers: Hodgkin 淋巴瘤 和 non-Hodgkin 淋巴瘤.

Soshnev的项目，"Underst和ing the Mechanism of Linker Histone Mutations in Malignancy,” received an Individual Investigator 研究 Award (IIRA), one of CPRIT’s most competitive grants. CPRIT awards IIRA funding to about 10% of the applications it receives.

According to the National Cancer Institute, there were more than a million people living with B-cell 淋巴瘤在2020年的美国. While several treatment options are available 和 the prognosis is generally positive, 淋巴瘤 five-year mortality rates range between 10 和 25% for different subtypes.

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“这很迷人。 that while your genetic code is largely unchanged in development, interpretation of this code is vastly different across cell types.”

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Soshnev’s research focuses on chromatin, a polymer complex comprised of DNA 和 associated proteins. Chromatin plays a critical role in all cellular processes where DNA is involved, 比如细胞分裂, DNA损伤修复与基因调控. 组蛋白是最丰富的一类染色质蛋白, 和 several classes of histones contribute to both structural 和 regulatory mechanisms in DNA.

“这很迷人。,索什涅夫说, “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’ 和 ‘repressive’ neighborhoods in the chromosomes.”  

Soshnev继续, “This project started as an attempt to answer a fundamental question—how are chromatin compaction, 基因表达, 组蛋白修饰相互关联. 然而, we quickly realized that these very fundamental questions have an immediate real-world application.”

Soshnev和合作者 最近发布了 that chromosome decompaction can precipitate a chain of events leading to malignant transformation, 和 over a third of patients diagnosed with B-cell 淋巴瘤 carry somatic (i.e. 编码H1组蛋白基因的肿瘤特异性突变.

Soshnev和他的团队将破译基因依赖性, 后果, 以及b细胞恶性肿瘤中H1缺失的脆弱性. Underst和ing 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 和 increasing the potential to progress into cancer,索什涅夫说. “然而, a lot of details of how H1 mutations lead to malignancy remain unknown 和 are something we’d like to learn more about. 除了H1突变型淋巴瘤, our findings will be immediately relevant to an emerging class of malignancies associated with aberrant chromatin decompaction.”

Soshnev获得了M.D. 从圣. Petersburg State University Faculty of Medicine in Russia 和 a Ph.D. in molecular 和 cellular biology from the University of Iowa. He joined 世界杯官方app as a faculty member in 2022 after completing a postdoctoral fellowship at 的 Rockefeller University in New York.

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的 Soshnev实验室 is interested in how information encoded in DNA is interpreted, modified 和 propagated. His team aims to underst和 how specific 基因表达 programs are established in development 和 how mutations in chromatin factors can lead to human disease.

CPRIT was formed in 2007 with an initial $3 billion investment from the state of Texas to fight against cancer. CPRIT现在是60亿美元, 20-year initiative 和 is the largest state cancer research investment in the history of the United States 和 the second largest cancer research 和 prevention program in the world.

— 瑞安Schoensee

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