# Equipment Supplement NOT-GM-24-021

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $111,039

## Abstract

Characterizing the Physiological and Pharmacological Roles of SLC22A24
Membrane transporters in the solute carrier superfamily (SLC) play critical roles in physiology and
pharmacology serving in the cellular uptake and removal of endogenous metabolites and many prescription
drugs. In spite of their importance, about one-fifth of SLC transporters have no known substrates and are
considered “orphan” proteins. Recently, our laboratory de-orphaned one of these proteins, SLC22A24, by
applying various methods, which included computational analyses of genomewide association signals,
homology modeling, expression profiling, and importantly, isotopic uptake assays in cells stably expressing
SLC22A24. Our studies revealed that SLC22A24 is an organic anion transporter with a preference for sulfate
and glucuronide conjugates of steroids. Recent preliminary studies suggest that the transporter also plays an
important role in drug disposition. The major goals of the proposed research are to determine the
physiological and pharmacological roles of SLC22A24 in the disposition of steroid glucuronides and to
discover other endogenous metabolites and pharmacologic agents that are substrates of SLC22A24.
To achieve our goals, we have designed three specific aims. In aim 1, we will employ studies in cell lines to
determine the localization of SLC22A24 to the basolateral or apical membranes. In addition, we will discover
prescription drugs and other metabolites that are substrates of SLC22A24. In aim 2, we will use CRISPR/Cas9
methods to create transgenic mice expressing SLC22A24 in the proximal tubule and use the mice to determine
its role in the disposition of pharmacologic and physiologic substrates of the transporter. Finally, in aim 3, we
will conduct association studies in healthy volunteers to associate functional variants in SLC22A24 with plasma
levels and renal clearance of steroid glucuronides. Methods employed will include confocal microscopy,
isotopic uptake and flux assays in cells, CRISPR/Cas9 methods in mice, LC/MS/ metabolomic analytical
methods, association analyses and clearance determinations in humans. We postulate that this
comprehensive genomic, metabolomic and functional studies in cells, mice and in healthy volunteers including
deep clinical phenotyping will serve as a blueprint for systematic evaluation of the physiological and
pharmacological roles of a newly de-orphaned transporter.

## Key facts

- **NIH application ID:** 11037661
- **Project number:** 3R01GM139875-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** KATHLEEN M GIACOMINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $111,039
- **Award type:** 3
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037661

## Citation

> US National Institutes of Health, RePORTER application 11037661, Equipment Supplement NOT-GM-24-021 (3R01GM139875-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037661. Licensed CC0.

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