Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Spatially-resolved, integrated cell state and lineage tracing to define progenitor cell dynamics in early mouse development

Award Number: K99HD118574
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Spatially-resolved, integrated cell state and lineage tracing to define progenitor cell dynamics in early mouse development - Project Summary: Mammalian development is a probabilistic and robust process where progenitor cells must integrate genetic, epigenetic, and environmental information to generate a complex body plan. The goal of this work is to delineate how progenitor behaviors elicit specific phenotypes in health and disease. To do so, I will leverage a technology I developed in my postdoctoral work in the Weissman lab, termed PEtracer, a prime editing-based tool that enables the 1) assessment of cell state and lineage using both imaging- and sequencing- based profiling methods, including spatially-resolved techniques, 2) precise perturbation of genomes for testing hypotheses about gene function, 3) studying these processes at scale in complex tissues, in 4) a manner that minimally affects normal cell function. To showcase the PEtracer system, I used it to study a xenograft model of breast cancer where I reconstructed the 3-dimensional growth patterns of a primary tumor and then uncovered how each cell’s interactions with its neighbors and microenvironment influenced its propensity to seed metastases. These important discoveries break novel ground in cancer biology and stand to inform therapeutic development. Here, I propose to leverage this technology in engineered mouse embryonic stem cells and mouse models to create the first integrated maps of cell state and lineage during normal development, biological ciphers that could be used to understand how tissues are assembled and maintained and how these processes go awry in disease. I will use in vitro stem cell-based gastruloid models where high replication power enables a statistical view of developmental processes and allows for perturbation studies to probe the genetic determinants of cell state and lineage decisions in development. I will also use mouse models to study these questions in the complete context of a developing organism. In the K99 training phase, I will develop expertise in stem cell biology, learn how to engineer mouse models, and sharpen computational skills needed to analyze the unique datasets these projects generate. I will learn these technical skills from my brilliant co-mentors, Dr. Jonathan Weissman and Dr. Zachary Smith, and my pioneering collaborators. Further, I will gain critical experience managing a growing research program during this time. The stem cell and mouse models I engineer during my K99 phase will be foundational for my R00 phase and beyond where I will study progenitor cell dynamics during mammalian development using both cutting-edge in vitro and in vivo model systems. I aim to study how the behaviors and histories of single cells lead to complex cell states and characteristics. This work will provide a foundation for my future research program as an independent investigator at a major research institution where I will use the spatially-resolved cell state and lineage maps of progenitor cellular dynamics in normal development that I generate through this K99/R00 award to understand how these same processes go awry in developmental disorders and diseases. This work that may unlock a new era of quantitative genomics in developmental biology and guide future translational research.


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 = $125,000 )
2026	2026	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	2	4/2/2026	NON-COMPETING CONTINUATION	$125,000
														Subtotal = $125,000

Issue Date FY: 2025 ( Subtotal = $125,000 )
2025	2025	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	1	2/20/2025	NEW	$125,000
														Subtotal = $125,000

Grand Total All Awards = $250,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Spatially-resolved, integrated cell state and lineage tracing to define progenitor cell dynamics in early mouse development

Award Number: K99HD118574

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer