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REGULATION OF EPITHELIAL HOMEOSTASIS BY UBIQUITIN-LIKE PROTEINS

Award Number: K08AR088167
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/10/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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REGULATION OF EPITHELIAL HOMEOSTASIS BY UBIQUITIN-LIKE PROTEINS - REGULATION OF SKIN HOMEOSTASIS BY UBIQUITIN-LIKE PROTEINS Diseases involving abnormal epidermal differentiation, such as psoriasis and atopic dermatitis, affect roughly 13% of Americans. This motivates understanding the mechanisms underlying epidermal homeostasis. Through multi-omic profiling, we identified ubiquitin-like (UBL) proteins as key biomolecular switches controlling keratinocyte fate. The NEDD8 UBL and its conjugation machinery maintains progenitors through effects on the proteome and transcriptome, whereas the SUMO2 UBL machinery is essential for differentiation. A long-term goal of my research is to understand the molecular switches that regulate epithelial homeostasis in health and disease. Therefore, this K08 proposal will elucidate how essential functions of these UBLs regulate RNA lifecycles and post-translational mechanisms in epithelial homeostasis. In Aim I, we will determine how NEDD8 sustains the keratinocyte progenitor state. Our preliminary data show that NEDD8 inhibition controls both ubiquitin-proteasome (UPS) concordant and UPS-independent proteomic alterations. Further, NEDD8 broadly controls progenitor and differentiation RNA life cycles. In Aim I.A, we will identify the NEDD8-dependent proteins essential for progenitor maintenance. In Aim I.B, we investigate the role of NEDD8 in controlling RNA stability, map the landscape of NEDD8 associated RNAs and characterize RNA dependent co-bound interactors. In Aim II, we will determine how SUMO2 plays its essential role in differentiation. Our data show that NEDD8 and SUMO2 converge on cell cycle control – SUMO2 is necessary for NEDD8 inhibition-induced cell cycle arrest. Further, both these UBLs bind the SUMO2 activating enzyme SAE1. SAE1 also binds free glucose and glucose levels alter SUMOylation dynamics. Therefore, we hypothesize that SAE1 serve as a regulatory hub where UBL crosstalk and environmental cues converge. In Aim II.A, we will dissect convergence of NEDD8 and SUMO2 on cell cycle control. In Aim II.B, we will evaluate how binding of free glucose control SAE1 activity and dimerization to enable epidermal differentiation. My background is in molecular biology, genetics and translational research. Over the course of the training period and within the environment of Stanford’s Department of Dermatology, I plan to acquire and deepen expertise in (1) epithelial biology, (2) bioinformatics and machine learning, (3) proteomics, and (4) statistics. My research interest in skin biology requires this broad skill set, and this K08 proposal will prepare me for an independent career as an academic scientist working on the multi-omic dissection of epithelial tissue regulation. This work will be performed at Stanford University under the mentorship of Dr. Paul Khavari, a physician-scientist and expert in epithelial biology. Altogether, my goal is to advance development of novel therapies and deepen the molecular understanding of pathways underlying epithelial homeostasis.


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 = $164,592 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/11/2026	NEW	$164,592
														Subtotal = $164,592

Grand Total All Awards = $164,592

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REGULATION OF EPITHELIAL HOMEOSTASIS BY UBIQUITIN-LIKE PROTEINS

Award Number: K08AR088167

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/10/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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