# Molecular mechanisms of sigma receptor signaling

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $324,679

## Abstract

Abstract
The sigma-1 receptor is an enigmatic transmembrane receptor in humans that has been implicated in a variety
of disease processes, including neurodegenerative disease and heart failure. Recently, the sigma receptor has
been identified as a regulator of ion channel and GPCR signaling. Despite the growing recognition of the
importance of this protein, very little is known regarding the molecular basis for its activity or its contribution to
disease. We will study the sigma receptor using a multifaceted approach to examine structure, pharmacology,
and dynamics of this important protein. Initial efforts will focus on the use of X-ray crystallography to probe
receptor activation mechanism using conformationally selective antibody fragments. Complementing this work,
we will explore the role of oligomerization in sigma receptor function using electron microscopy and other
methods, and we will characterize the structural dynamics of the receptor by NMR spectroscopy and
computational simulations. In the long term, we aim to establish a detailed molecular understanding of the
sigma receptor activity and its role in human health and disease.

## Key facts

- **NIH application ID:** 9906922
- **Project number:** 5R01GM119185-04
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Andrew Kruse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,679
- **Award type:** 5
- **Project period:** 2017-08-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906922

## Citation

> US National Institutes of Health, RePORTER application 9906922, Molecular mechanisms of sigma receptor signaling (5R01GM119185-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9906922. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*