# MOLECULAR ASPECTS OF AMYLOIDOSIS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1992 · $174,443

## Abstract

A mammalian multigene family, the serum amyloid A (SAA) gene family, is
differentially regulated during inflammation.  There are three
functional genes in this family -- SAA1, 2, and 3 -- and a structurally
related pseudogene.  Upon induction, the level of SAA mRNA in the liver
and the concentration of SAA in plasma can increase as much as 1,000-
fold.  Though we know that SAA expression is regulated during
inflammation, at least in part, by the circulating inflammatory cytokine
interleukin-1 (IL-1) and that NFkappaB- and C/EBP-related transcription
factors are important for its expression, we know few molecular details
about its differential regulation and tissue-specific expression during
inflammation and the precise roles of these transcription factors.  The
diverse features of this differential expression during inflammation,
together with the differential response by members of the SAA gene
family in different tissues, make the SAA gene family a particularly
informative model to examine the molecular mechanism underlying the
complexity of gene control.  The overall objective of our research
program is to understand the molecular mechanisms involved in the
transcriptional regulation of SAA genes.  We hypothesize that multiple
regulatory mechanisms, including induction and repression mechanisms,
are likely to exist in order to establish the appropriate physiological
levels of SAA during inflammation.  Furthermore, these mechanisms must
involve regulatory DNA sequences and their interactions with sequence-
specific trans-regulatory factors.  Our studies on the SAA genes support
these hypotheses and have identified both positive and negative
regulatory elements and their corresponding sequence-specific binding
proteins.  Given the unique opportunity to study the differential
regulation of the SAA genes, we will also focus our studies on the
comparisons of these genes.  Such studies have the potential to generate
new insights into the molecular evolution of regulatory mechanisms
elicited by inflammatory cytokines and tissue-specific control and may
in turn lead to increased understanding of inflammatory processes and
ways to modulate them.  The Specific Aims for our studies are:

1).  To develop an in vitro transcription system which demonstrates
inducible, cell-type specific transcription following stimulation; 2.)
To examine the molecular basis of differential regulation of SAA1 and
SAA3 genes; 3.) To characterize and purify tissue-specific repressor and
to clone its cDNA; 4.) To examine the involvement of C/EBP family
proteins in SAA gene regulation.

## Key facts

- **NIH application ID:** 3158845
- **Project number:** 2R01AR038858-06
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** Warren S. LIAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $174,443
- **Award type:** 2
- **Project period:** 1987-09-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158845

## Citation

> US National Institutes of Health, RePORTER application 3158845, MOLECULAR ASPECTS OF AMYLOIDOSIS (2R01AR038858-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158845. Licensed CC0.

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