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Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

Award Number: R35GM133758
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin - PROJECT SUMMARY Changes occurring during embryogenesis are typically lethal or can lead to congenital malformations. In many cases, however, these changes can be beneficial because they can promote the origin of new traits and the evolution of adaptations. Because of this relationship between deleterious and viable variation, studying naturally occurring phenotypic diversity across the animal kingdom provides a powerful framework to study a fundamental question in developmental biology and biomedical sciences: How can development change without detrimental consequences? Our laboratory harnesses natural variation in mammalian skin to understand how changes during development can generate phenotypic variation. Through work funded by my Early-Stage Investigator R35, we have studied two distinct spatially patterned phenomena during skin development: (1) Stripe pattern formation in rodents, and (2) Gliding membrane formation in marsupials. As proven by our track record, this work has significantly advanced our understanding of the mechanisms by which skin is patterned. In the new funding period, we will focus on studying stripe pattern formation in rodents to uncover the mechanisms by which skin can acquire positional information and how such mechanisms have been modified across evolutionary time to produce different phenotypic outcomes. To achieve this, we will build on our solid findings from previous studies, on our exciting new preliminary data, and on the wide array of genomic and molecular tools that my laboratory has already developed. First, using the African striped mouse as a model, we will investigate the mechanisms by which pigment patterns are established and implemented. Specifically, we will uncover how a Wnt signaling gradient in the dorsal skin is established; how spatiotemporal dynamic patterns of gene expression are achieved, and what is the contribution of different hair follicle cell types to modulating differences in coat color. Then, using a comparative approach, we will study how pigment patterns can diverge. In particular, we will study how differences in placode patterning across species are established and we will uncover the regulatory mechanisms by which spatial differences in pigmentation gene expression can be achieved. The approaches described in this research program integrate multiple disciplines, including developmental biology, functional genomics, and computational biology, with my lab’s expertise in skin developmental biology and demonstrated success developing molecular tools in emerging model species.


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: 2025 ( Subtotal = $513,550 )
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	001	6	5/30/2025	COMPETING CONTINUATION	$513,550
2025	2023	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	5	5/22/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $513,550

Issue Date FY: 2023 ( Subtotal = $396,930 )
2023	2023	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	5	9/13/2023	NON-COMPETING CONTINUATION	$396,930
														Subtotal = $396,930

Issue Date FY: 2022 ( Subtotal = $396,930 )
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	4	8/29/2022	NON-COMPETING CONTINUATION	$396,930
														Subtotal = $396,930

Issue Date FY: 2021 ( Subtotal = $396,930 )
2021	2021	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	3	8/31/2021	NON-COMPETING CONTINUATION	$396,930
														Subtotal = $396,930

Issue Date FY: 2020 ( Subtotal = $396,930 )
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	2	8/25/2020	NON-COMPETING CONTINUATION	$396,930
														Subtotal = $396,930

Issue Date FY: 2019 ( Subtotal = $397,011 )
2019	2019	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	1	9/13/2019	NEW	$397,011
														Subtotal = $397,011

Grand Total All Awards = $2,498,281

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Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

Award Number: R35GM133758

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/13/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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