# The role of cortisol synthesis in pathogenesis of Hidradenitis suppurativa tunnels

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $466,198

## Abstract

Abstract
Hidradenitis suppurativa (HS) is a common, debilitating inflammatory disease characterized by unique
pathological features that includes epithelialized tunnel formation. Chronically draining, intradermal tunnels are
unique feature of HS pathology and contribute to robust inflammation significantly affecting patients’ quality of
life. Tragically, no consistently effective treatments exist for HS tunnels. In addition, the progress in the field is
hampered by the lack of clinically relevant HS models. We assembled a multidisciplinary collaborative team
with unique and complementary expertise in HS, 3D skin models, glucocorticoid synthesis and signaling. The
team generated preliminary data obtained from patients’ tissue specimens: samples from HS tunnel, lesional
skin above the tunnel, along with the age, gender, and location-matched healthy skin controls and found that
cortisol and steroid synthesis pathways are markedly suppressed in HS tunnels, leading to perpetual pro-
inflammatory keratinocyte activation. We also found lack of glucocorticoid receptor (GR) activation in HS
tunnels, which was supported by HS transcriptomics signature characterized by marked downregulation of
cortisol synthesis and GR signaling, again uniquely associated with the tunnels and not observed in lesional
keratinocytes. Importantly, we successfully developed the first 3D organotypic model from primary HS tunnel
keratinocytes and fibroblast that recapitulates tunnels structure in patients. Based on the robust preliminary
and published data, we propose a novel concept of HS tunnel as an intradermal perpetual cellular activation
process, in which its deregulation, in particular lack of cortisol synthesis, is a major contributor to
pathophysiology. Further, we hypothesize that inhibition of epidermal and dermal cortisol production coupled
with dysfunctional cellular activation play a central role in HS tunnel pathogenesis. To test this, we outlined
three Aims which will utilize a) tissue and b) primary cell obtained from HS patients in distinct locations: HS
tunnels, skin above the tunnel, perilesional skin (all from the same patient) and location, age, sex, ethnicity
matched controls; c) organotypic 3D HS tissue generated from these primary cells. HS tissue, cells and
organotypic cultures will be maintained under normoxia and hypoxic conditions and challenged by insult and
Aim 1 will determine the role of cortisol synthesis in HS tunnels and 3D organoids by using spatial
transcriptomics and measuring cortisol production, whereas the other two Aims will offer mechanistic insights
that can reveal potential new therapeutic avenues. Aim 2 will test if targeting cortisol synthesis can restore the
function of tunnel keratinocytes and fibroblasts and their activation, whereas Aim 3 will focus on how genomic
and non-genomic GR signaling contributes to pathophysiology of HS tunnels and HS in general. Better
understanding the mechanisms through which cortisol synthesis and G...

## Key facts

- **NIH application ID:** 10980978
- **Project number:** 1R01AR083385-01A1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Hadar Lev-Tov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,198
- **Award type:** 1
- **Project period:** 2024-09-02 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980978

## Citation

> US National Institutes of Health, RePORTER application 10980978, The role of cortisol synthesis in pathogenesis of Hidradenitis suppurativa tunnels (1R01AR083385-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980978. Licensed CC0.

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