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Elucidating the role of interferon gamma production and signaling in the generation of neuropathic pain in human dorsal root ganglia

Award Number: F32NS134563
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: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Elucidating the role of interferon gamma production and signaling in the generation of neuropathic pain in human dorsal root ganglia - Project Summary Neuropathic pain is a major healthcare concern in the US due to its prevalence and high-cost through healthcare treatment and lost wages. Molecular techniques have been utilized on human dorsal root ganglia (hDRG) to better understand mechanisms underlying neuropathic pain to lead to the development of novel therapeutics. This work has demonstrated a sex-specific neuroimmune mechanism in which females show increased expression of interferon gamma (IFNγ) induced genes. IFNγ is a pro-inflammatory cytokine known for its anti-viral effects which recently has been shown to produce neuro-inflammation and pain. In animal models, intrathecal delivery of IFNγ produces paw hypersensitivity, and animals lacking the IFNγ receptor (IFNGR) fail to produce hyperalgesia following induction of neuropathic pain. Thus, this combined data suggests a potential female specific role of IFNγ in the hDRG to produce neuropathic pain. Elucidation of IFNγ mechanisms can lead to the production of sex-specific therapeutics for the treatment of neuropathic pain. I propose to use hDRG neurons to examine the role of IFNγ in the production of changes consistent with the development of neuropathic pain. Specific Aim 1 will explore which immune cells present in hDRGs are capable of producing IFNγ. I will do this through fluorescently activated cell sorting of hDRG neurons of both sexes to isolate CD4 and CD 8 T cells and monocytes. Then, I will perform RNA sequencing and proteomic assessments to determine which immune cells possess genes and proteins responsible for IFNγ production and if any sex differences exist. Then, I will perform a ligand-receptor interactome analysis with the RNA sequencing and proteomic data sets of each immune cell subtype. This will lead to the generation of testable hypotheses through which each immune cell can interact with hDRG neurons to lead to the production of neuropathic pain and if differences exist between the sexes. In Specific Aim 2, I will perform a comprehensive assessment of the impact of IFNγ signaling on hDRG neurons. In these experiments, I will culture hDRG neurons of each sex and expose them to IFNγ. First, I will look at the functional impact of IFNγ on hDRG neurons by using calcium imaging to see if IFNγ can excite and/or sensitize hDRG neurons to later prostaglandin exposure. Then, I will again expose cultured hDRG neurons to IFNγ and isolate RNA and protein to perform bulk and single cell RNA sequencing and phosphoproteomic assessment. This will give unprecedented insight into how hDRG neurons respond functionally, transcriptionally, and proteomically to IFNγ exposure and if any differences exist between the sexes. In sum, this work can lead to the production of novel, sex-specific therapeutics for the treatment of neuropathic pain. This work will also provide substantial scientific and bioinformatic training vital to me reaching my long-term career goal of becoming an independent, translational researcher as a PI at a large academic institution conducting next generation sequencing and other omic experiments on human tissue.


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: 2026 ( Subtotal = $80,224 )
2026	2026	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	2/23/2026	NON-COMPETING CONTINUATION	$80,224
														Subtotal = $80,224

Issue Date FY: 2025 ( Subtotal = $78,040 )
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	2	2/13/2025	NON-COMPETING CONTINUATION	$76,756
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	001	2	8/14/2025	NON-COMPETING CONTINUATION	$1,284
														Subtotal = $78,040

Issue Date FY: 2024 ( Subtotal = $73,828 )
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	002	1	1/5/2024	NEW	$0
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	003	1	6/14/2024	NEW	$4,748
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	1	1/5/2024	NEW	$69,080
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	1	1/5/2024	NEW	$0
														Subtotal = $73,828

Grand Total All Awards = $232,092

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Elucidating the role of interferon gamma production and signaling in the generation of neuropathic pain in human dorsal root ganglia

Award Number: F32NS134563

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: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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