# Transporter Elucidation Center at the University of California, San Francisco

> **NIH NIH UC2** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $959,082

## Abstract

PROJECT SUMMARY
Membrane transporters in the Solute Carrier (SLC) and ATP Binding Cassette (ABC) superfamilies play essential
roles in the transmembrane movement of solutes including drugs, dietary supplements and nutrients.
Transporters on the polarized membranes of epithelial cells such as those in the placenta, mammary gland and
gut or polarized endothelial cells such as those of the Blood Brain Barrier (BBB) play essential roles in
transcellular flux of their substrates. A significant gap in our understanding of both SLC and ABC transporters
exists as many transporters have not been systematically characterized and the range of substrates is not known
or poorly understood. In response to RFA-HD-23-003, we propose to establish a multi-disciplinary Transporter
Elucidation Center at the University of California San Francisco (TECUCSF), which brings together expert
scientists in transporter biology and pharmacology, membrane transporter structural biology, computational
biology, and chemo-informatics. The overall goal of the TECUCSF is to elucidate the ligand specificity, protein
structure and cellular localization of SLC and ABC transporters in the human BBB. Based on preliminary studies
from our global proteomic analyses, we will prioritize a list of 30 highly expressed and understudied/orphan SLC
and ABC transporters in the human BBB (BBB-30). Key knowledge gaps of these 30 transporters will be
addressed by research conducted under three aims. For Aim 1, we will perform in silico docking of neuroactive
drugs, nutrients, and dietary supplements using experimentally determined structures or structures based on
computed structural models of transporters in the BBB-30. For each of these transporters, we will create
recombinant cell lines expressing the transporter and functional assays to validate the in silico results, which will
result in the discovery of ligands for both understudied and orphan transporters. For Aim 2, we will use cryoEM
to determine the structure of selected transporters in the BBB-30, which do not have available structures. Finally,
for Aim 3, we will perform localization of the BBB-30 in human endothelial cell models using available antibodies
and flux studies will be performed to confirm the localization. To support our studies and enhance studies in the
Transporter Elucidation Network (TEN), three cores will be established: TECUCSF Informatics and Modeling Core;
TECUCSF Structure Core; and TECUCSF Function Core. The cores will provide support for research proposed in
each of the three aims, as well for investigators in the TEN. TECUCSF will work together with other TECs within
the TEN to generate knowledge and resources that will be shared with the broader research community through
RESOLUTE to advance our understanding of nutrient, drug, and dietary supplement constituent transport across
the BBB.

## Key facts

- **NIH application ID:** 10931758
- **Project number:** 5UC2HD113474-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** KATHLEEN M GIACOMINI
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $959,082
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931758

## Citation

> US National Institutes of Health, RePORTER application 10931758, Transporter Elucidation Center at the University of California, San Francisco (5UC2HD113474-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931758. Licensed CC0.

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