# MONOCLONAL ANTIBODIES TO HUMAN EPIDERMIS

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1991 · $383,127

## Abstract

The general hypothesis is that there are discrete defects in the normal
pathway of epidermal differentiation related to the phenotypic changes
associated with genetic and acquired diseases of the epidermis, such as
psoriasis, the ichthyoses and Darier's disease.  The long-term focus of
this research is defining those defects ultimately leading to safe and
effective therapies for those disorders.  Retinoids have profound effects
on the normal and diseased epidermis and detailed studies of their action
on three different representative steps in epidermal maturation is planned;
differentiation limiting or modifying events involving a new human
homeobox-containing gene Hox 1.1; modulation of the epidermal growth factor
receptor (EGFR); and control of late events in terminal differentiation
catalyzed by intracellular transglutaminases.  The detailed specific aims
are:  1) Determine the molecular mechanism regulating the response of the
EGFR in cervical carcinoma cells ME-180 treated with retinoic acid (RA).
The half-life of mRNA will be determined in control cells and after
treatment with RA. Regulatory regions of the EGFR and other retinoid
inducible genes will be transfected into ME-180 cells which are then
treated with RA.  A promoter from the EGFR gene of ME-180 cells will be
ligated to CAT reporter gene constructs and transfected into normal
keratinocytes and other epithelial cells and the response to RA
quantitated.  The mRNAs for retinoid nuclear receptors will be measured.
Transcription factors controlling the RA response will be determined by gel
retardation and footprinting assays.  2) Determining the role of human Hox
1.1 in normal and altered epidermal differentiation.  The expression of Hox
1.1 in normal and altered epidermal differentiation.  The expression of Hox
1.1 in normal and altered epidermal differentiation.  The expression Hox
1.1 will be determined, by using in situ hybridization, in human fetal skin
samples of different gestational ages and in human skin biopsies of
normals, and patients with acne, psoriasis and genetics disorders of
keratinization, and in patients treated with systemic and topical RA.
Genomic clones for Hox 1.1 will be isolated and the 5' untranslated region
of the Hox 1.1 gene will be characterized and sequenced.  The detailed
chromosomal mapping of the gene will continue.  3) Determine the genetic,
biochemical and physiological relationships between the epidermal
transglutaminases.  Using the current transglutaminase cDNA clones from a
human epidermis cDNA library full length cDNA will be produced and genomic
transglutaminase characterized, especially its 5' nontranslated region.
The promoter and enhancer sequences will be characterized looking for
sequences known to be found in other epidermal genes responsive to
retinoids and other pharmacological agents.

## Key facts

- **NIH application ID:** 3155937
- **Project number:** 5R01AR030965-11
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** LOWELL Alan GOLDSMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $383,127
- **Award type:** 5
- **Project period:** 1990-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155937

## Citation

> US National Institutes of Health, RePORTER application 3155937, MONOCLONAL ANTIBODIES TO HUMAN EPIDERMIS (5R01AR030965-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155937. Licensed CC0.

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