# Role of autophagy in epidermal differentiation and homeostasis

> **NIH NIH K08** · UNIVERSITY OF WASHINGTON · 2021 · $136,294

## Abstract

Project Summary/Abstract
 Research: Epidermal homeostasis relies on two balanced processes: (1) mitotic keratinocytes in the basal
layer must maintain healthy organelles despite damage due to aging and ultraviolet radiation in order to
continually regenerate the upper layers and (2) post-mitotic cells in the outer layers must degrade organelles to
form a compact, protective barrier for the body. The mechanisms governing these fundamental processes are
poorly understood and this hampers our ability to restore epidermal barrier function in diseases like ichthyosis
and atopic dermatitis and to prevent skin carcinogenesis and aging. My research will test the hypothesis that
the epidermis relies upon autophagy pathways to drive organelle degradation as a constitutive process during
cornification and in an inducible manner to repair damaged organelles. The proposed experiments apply
super-resolution microscopy to image single organelle dynamics and degradation in live epidermis. The results
will improve our understanding of the role of autophagy in epidermal homeostasis and differentiation and could
suggest novel clinical uses of autophagy modulators for treatment of skin disease.
 Candidate: Cory Simpson earned his M.D. and Ph.D. from Northwestern Univ. in 2012, completed clinical
dermatology training at the Univ. of Pennsylvania in 2016, and sees patients with blistering disease, barrier
disorders, and skin cancer. Dr. Simpson is pursuing post-doctoral training in the lab of Dr. Erika Holzbaur,
Ph.D., where he is coupling live organotypic human and murine skin with innovative microscopy approaches.
The career development plan will allow Dr. Simpson to build on his training in keratinocyte biology to establish
an independent research program defining mechanisms of organelle degradation during epidermal
differentiation and upon environmental damage. Support from a K08 award will position Dr. Simpson to attain
his goal of becoming an R01-funded investigator directing an academic lab focused on modulating keratinocyte
organelle turnover to augment skin barrier function and prevent aging- and UV radiation-induced skin damage.
 Environment: The mentor, Dr. Holzbaur, is an NIH-funded Penn professor who provides (1) renowned
expertise in organelle trafficking and autophagy in disease models, (2) unrivaled live cell imaging experience
and state-of-the-art microscopes, and (3) exceptional mentorship of prior trainees including K08 recipients. Dr.
Simpson’s application of Dr. Holzbaur’s toolkit to epidermis provides a natural independence from her focus on
neurodegeneration. Dr. Holzbaur’s guidance will be complemented by a committee of new and established
investigators with expertise in cutaneous biology, intravital microscopy, and physician-scientist training. The
K08 proposal includes training in novel imaging techniques, new exposure to in vivo models, and coursework
in advanced/quantitative microscopy. Penn offers an outstanding Dermatology faculty with op...

## Key facts

- **NIH application ID:** 10543010
- **Project number:** 7K08AR075846-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Cory L Simpson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $136,294
- **Award type:** 7
- **Project period:** 2021-12-21 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543010

## Citation

> US National Institutes of Health, RePORTER application 10543010, Role of autophagy in epidermal differentiation and homeostasis (7K08AR075846-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10543010. Licensed CC0.

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