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Sigma 2 Receptor (TMEM97): Investigating the Peripheral Role of this Novel Therapeutic Target for Pain

Award Number: F31NS129269
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Sigma 2 Receptor (TMEM97): Investigating the Peripheral Role of this Novel Therapeutic Target for Pain - PROJECT SUMMARY Chronic pain affects greater than 50 million individuals with a huge economic burden. Currently, there are few effective treatments other than opioid-based drugs and non-steroidal anti-inflammatory drugs. Many of these treatments have a high potential for abuse and/or side effects. It is necessary to discover and study novel biological targets for the treatment of acute and chronic pain. This proposal focuses on an old molecular target, the Sigma 2/transmembrane protein 97 (σ2/TMEM97) receptor, that has been linked to pain only in the last five years. The σ2/TMEM97 receptor is an endoplasmic reticulum and plasma membrane transmembrane protein with known effects in cholesterol metabolism and calcium homeostasis. Recent behavioral pharmacology studies investigated σ2/TMEM97 as a potential therapeutic target for the treatment of pain and demonstrated that σ2/TMEM97-selective ligands were able to reverse neuropathic injury-induced mechanical hypersensitivity in mice. Neither the cellular mechanisms of this effect nor the anatomical location of the effects have been identified. In fact, limited knowledge in the context of pain of the cellular properties of σ2/TMEM97 and pharmacological properties of its ligands has been a barrier to accurately interpreting pharmacological behavioral effects. To advance the previous studies on σ2/TMEM97 as a therapeutic target for pain treatment, I aim to investigate the extent to which σ2/TMEM97 plays in the processing of nociception at the behavioral, cellular, and molecular level. I will investigate the role of σ2/TMEM97 by utilizing transgenic animals to examine the difference in cellular activity and the molecular profile of σ2/TMEM97-driven nociception in the peripheral nervous system (PNS). The goal of this proposal is to 1) understand the cellular and molecular signature of σ2/TMEM97- associated behavioral nociception in chronic inflammatory pain and 2) determine whether nociceptor-specific loss of σ2/TMEM97 function results in behavioral changes associated with perturbation to the PNS. This project includes significant training opportunities in molecular biology, animal behavior, and RNA sequencing data analysis preparing the PI for an independent career in neuroscience and biomedicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $40,600 )
2025	2025	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/13/2025	NON-COMPETING CONTINUATION	$40,600
														Subtotal = $40,600

Issue Date FY: 2024 ( Subtotal = $45,144 )
2024	2024	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/17/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/12/2024	NON-COMPETING CONTINUATION	$43,864
														Subtotal = $45,144

Issue Date FY: 2023 ( Subtotal = $43,423 )
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	12/12/2022	NEW	$0
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/12/2022	NEW	$42,481
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	2/14/2023	NEW	$942
														Subtotal = $43,423

Grand Total All Awards = $129,167

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Sigma 2 Receptor (TMEM97): Investigating the Peripheral Role of this Novel Therapeutic Target for Pain

Award Number: F31NS129269

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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