Functional consequences of Loss Of Y (LOY) in men with Alzheimer’s disease and cancer; multi-omics study
Description: Loss of chromosome Y (LOY) is a frequent mutation in adult males, linked to an increased risk of morbidity and mortality from various age-related diseases. Many studies performed by us and others showed that LOY observed in the blood of men is associated with cancer, Alzheimer´s disease (AD), and even higher severity of COVID-19 disease, supporting the role of LOY in disturbance of the immune system in men. Therefore, the aim is to conduct functional studies that will determine how LOY in tissue-infiltrating and circulating leukocytes affects the development of colorectal cancer (CRC) and AD. Our recent data show that LOY frequently occurs in T regulatory lymphocytes (Tregs) in the tumor microenvironment of CRCs and in NK-cells in AD patients and we will study these aspects further. Therefore, we will perform a comprehensive analysis of LOY in leukocytes and different types of tissues (postmortem brain tissues, tumor, and adjacent normal tissue samples) by implementing multi-omics technologies, such as genomics, transcriptomic, and proteomics, providing information about the consequences of LOY in men with AD and CRC. We want to investigate whether cells with LOY may disturb the proper function of immune surveillance and what is the molecular mechanism behind this. This research will bring insights into the role of LOY in the development and progression of CRC and AD. This will pave the way for improved early diagnosis and better opportunities for treatment.
Funder: Vetenskapsrådet
Amount: SEK 2,400,000
Funding type: research
Funder scheme: Project grant
Start date: 2024-01-01
End date: 2026-12-31
Investigator: Jan Dumanski
Institution: Uppsala University
Funded outputs count: 0
Funder award ID: 2023-01940
OpenAlex ID: G511169208