# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2021 · —

## Abstract

Dr. Lau is an internationally recognized investigator in the Y chromosome biology and an established
expert in molecular genetics and transgenic mouse modeling of human diseases. He has established various
molecular tools in his laboratory, installed advanced next generation sequencing equipment and bioinformatics
in the Molecular Core, and served as consultant for PIs interested in such advanced technologies at the SFVA.
Currently, he has several established and pilot projects. First project focuses on the roles of the Y-located
proto-oncogene TSPY in liver and prostate cancers. TSPY is the gene for the gonadoblastoma locus on the Y
chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Normally, it functions as a
male germ stem cell factor, but as an oncogene when ectopically expressed in somatic cells, such as prostate
epithelial cells and hepatocytes. It stimulates cell proliferation and cyclin B-CDK1 kinase activities. TSPY forms
a positive feedback loop with male sex hormone receptor AR and constitutively active variant AR-V7, thereby
amplifying their respective oncogenic actions. Research centers on exploring the correlation between TSPY,
AR/AR-V7 expression and clinical features and outcomes in liver and prostate cancers; and on studying
experimentally the contributions of TSPY and AR/AR-V7 in oncogenesis in liver and prostate cancer. Validation
of the roles of TSPY in AR/AR-V7 in the male-dominance in liver cancer could offer immediate translational
applications of effective anti-AR/AR-V7 drugs already developed for prostate cancer to the treatment of liver
cancer. The second project focuses on the X-located homologue of TSPY, TSPX on human oncogenesis. Due
to evolutionary divergence, TSPX possesses contrasting properties, i.e. retards cell proliferation, inhibits cyclin
B-CDK1 and AR/AR-V7 transactivation activities, and behaves as a tumor suppressor in various cancers,
including lung, liver and prostate cancers. Studies are designed to identify their respective oncogenic and
tumor suppressor domains, and signaling pathways in oncogenesis. The third project focuses on the genes on
the male-specific region of the Y chromosome (MSY) in sex differences in various physiology and diseases.
The current emphasis is on the sex-determining gene SRY, which is essential for sex determination, but not for
the development of non-gonadal tissues. Dr. Lau has established an efficient transgene activation system and
demonstrated that aberrant expression of a human SRY induces various abnormalities in transgenic mice,
including retardation in neurogenesis and postnatal lung development, nonalcoholic fatty liver disease and
myocardial infarction. Studies are being conducted to characterize the mechanisms of diseases, mediated by
aberrant SRY expression in the respective tissues. The fourth project focuses on the recently observed link
between mosaic loss of the Y chromosome (mLOY) in the peripheral blood and increased risks and mort...

## Key facts

- **NIH application ID:** 10047239
- **Project number:** 5IK6BX004854-02
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** YUN-FAI CHRIS LAU
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10047239

## Citation

> US National Institutes of Health, RePORTER application 10047239, BLR&D Research Career Scientist Award Application (5IK6BX004854-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10047239. Licensed CC0.

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