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Granulosa-derived RNAs as targets for oocyte rejuvenation

Award Number: K99HD120651
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Granulosa-derived RNAs as targets for oocyte rejuvenation - PROJECT SUMMARY Oocyte quality-related infertility is a major economic and social burden. The current explanation for age-related decline in oocyte quality is that oocytes accumulate irreversible damage and lose the potential to give rise to offspring over time. However, emerging experimental evidence demonstrates that the ovarian microenvironment also plays a role in oocyte maturation outcomes. In my postdoctoral work I have shown that mouse somatic granulosa cells transfer mRNAs to oocytes and that many of these transcripts are important for oocyte maturation and early embryogenesis. Based on these findings, this proposal will investigate the hypothesis that poor oocyte maturation outcomes arise from insufficient transcriptional support from the granulosa cells. This hypothesis will be tested in three independent aims. In the first aim I will interrogate the mechanism by which RNAs are transferred from granulosa cells to oocytes. We believe that RNAs are either packaged in vesicles and trafficked along the transzonal projections that connect granulosa cells to oocytes or passed from granulosa cells to oocytes via transient membrane fusion events. In the second aim I will use in vivo transgenic approaches to uncover which mRNAs are transferred and in what amount they must be transferred to support different stages of oocyte growth. For the third aim we will develop a protocol to supplement oocytes with in vitro transcribed RNAs. We will test whether this improves maturation outcomes in both human and mouse germinal vesicle stage oocytes. This research plan is designed to characterize the mechanistic cell biology of granulosa-derived RNA support and to develop interventions that improve outcomes for oocyte quality-related infertility patients. To achieve these experimental goals, I will be supplementing the guidance of my postdoctoral advisor, Dr. Diana Laird, with a group of co-mentors and collaborators with sophisticated skillsets outside of my personal expertise. I will be co-mentored by Dr. Robert Blelloch, an expert in the biology of how vesicle packaged RNAs regulate cancer progression, and Dr. Eszter Posfai, an expert in mouse embryo manipulation and transgenesis. I will be collaborating with Dr. Steven Munger, an expert in mapping genetic variation in outbred mouse populations, and Dr. Marcelle Cedars, a physician-scientist who will be assisting our efforts to translate our findings into oocyte rejuvenation technologies. My work on in vitro maturation will also be consulted on by Dr. Marco Conti, an expert in oocyte maturation with over 40 years of experience working in the field. Together with my mentors, collaborators, and consultants I have developed a plan for gaining the expertise needed to finish my postdoctoral studies and transition to a career as a tenure-track principle investigator.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $123,147 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Child Health and Human Development Extramural Research	000	1	8/18/2026	NEW	$123,147
														Subtotal = $123,147

Grand Total All Awards = $123,147

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Granulosa-derived RNAs as targets for oocyte rejuvenation

Award Number: K99HD120651

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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