Tuesday, July 1, 2025 7/1/2025

The Impact of Pten Signaling on Neuronal Form and Function

Award Number: R01MH097949
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

The Impact of Pten Signaling on Neuronal Form and Function - Abstract PTEN is a phosphatidylinositol phosphatase that antagonizes signaling downstream of growth factor receptors. Mutations in PTEN have been identified in patients with autism spectrum disorder (ASD) and macrocephaly. Further, experimental deletion of Pten in the mouse brain causes macrocephaly and deficits in social behavior, suggesting a causative role in the development of ASD. In neurons, Pten knockout results in aberrant growth and increased excitatory synaptic function. Thus, studying Pten fits with our long-term goal of understanding how synaptic connectivity and activity contribute to cognitive and emotional functions. My central hypothesis is that PTEN dysfunction causes aberrant neuronal growth leading to altered synaptic circuit formation during development. Guided by this hypothesis, the specific aims of this proposal will strengthen our understanding of the molecular and neurophysiological basis of ASD. Manipulation of Pten in vivo presents a unique opportunity to examine the neurophysiological basis of ASD in a model organism. Our first aim will test our central hypothesis by determining the downstream signaling intermediates necessary for neuronal growth, synapse formation, and increased excitability after Pten knockout. We have discovered that cytoskeletal polymerization rate is increased in dendritic growth cones of neurons lacking Pten. We hypothesize that the change in polymerization rate is not dependent on mTORC1 or protein synthesis and therefore represents a parallel molecular pathway that could be targeted for treatment. Understanding the molecular mechanisms underlying these cellular phenotypes could lead to new treatments for ASDs. Our second aim will define how PTEN dependent cytoskeletal polymerization contributes to neuronal growth and synapse function and test if this is mTORC2 dependent. A gap in our understanding of neuronal cell biology exists because signaling downstream of Pten has been largely defined in immortalized cell lines. Thus, we do not know the requirements for specific signaling intermediates regulating translation and cytoskeletal remodeling in specialized processes such as dendritic branching, filopodial growth, and synapse formation. I hypothesize that PTEN function must be regulated in distinct subcellular compartments to regulate soma migration and growth versus dendritic growth and synapse formation. For the third aim, we will test subcellular localization of PTEN necessary to regulate neuronal growth, synapse formation, and synapse function. This proposal will use innovative genetic approaches to both knockout endogenous mouse genes and replace them with mutated forms in vivo. The strategy of gene knockout and molecular substitution will allow us to test specific mechanisms regulating neuronal development and function. The broad goal of this research is to understand the molecular basis of neuronal dendritic arborization facilitating synaptic contact and function.


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 = $529,704 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	001	14	4/25/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$529,704
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	003	14	5/1/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$257,471
2025	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	002	13	5/1/2025	NON-COMPETING CONTINUATION	-$257,471
2025	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	13	4/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $529,704

Issue Date FY: 2024 ( Subtotal = $666,112 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	13	3/13/2024	NON-COMPETING CONTINUATION	$599,502
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	13	8/16/2024	NON-COMPETING CONTINUATION	$66,610
														Subtotal = $666,112

Issue Date FY: 2023 ( Subtotal = $666,112 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	12	4/4/2023	NON-COMPETING CONTINUATION	$666,112
														Subtotal = $666,112

Issue Date FY: 2022 ( Subtotal = $682,112 )
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	6001 PARKHURST HALL STE 207	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	11	3/4/2022	COMPETING CONTINUATION	$615,501
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	11	6/27/2022	COMPETING CONTINUATION	$66,611
2022	2021	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	002	10	8/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $682,112

Issue Date FY: 2021 ( Subtotal = $450,559 )
2021	2021	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	10	3/12/2021	NON-COMPETING CONTINUATION	$450,559
2021	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	9	10/23/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $450,559

Issue Date FY: 2020 ( Subtotal = $450,559 )
2020	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	9	3/24/2020	NON-COMPETING CONTINUATION	$450,559
														Subtotal = $450,559

Issue Date FY: 2019 ( Subtotal = $450,559 )
2019	2019	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	8	6/11/2019	NON-COMPETING CONTINUATION	$0
2019	2019	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	8	3/6/2019	NON-COMPETING CONTINUATION	$450,559
														Subtotal = $450,559

Issue Date FY: 2018 ( Subtotal = $450,559 )
2018	2018	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	7	3/22/2018	NON-COMPETING CONTINUATION	$405,503
2018	2018	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	7	6/17/2018	NON-COMPETING CONTINUATION	$45,056
														Subtotal = $450,559

Issue Date FY: 2017 ( Subtotal = $474,270 )
2017	2017	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	6	5/22/2017	COMPETING CONTINUATION	$474,273
2017	2016	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	5	5/8/2017	EXTENSION WITH OR WITHOUT FUNDS	-$3
														Subtotal = $474,270

Issue Date FY: 2016 ( Subtotal = $405,000 )
2016	2016	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	5	3/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$405,000
														Subtotal = $405,000

Issue Date FY: 2015 ( Subtotal = $405,000 )
2015	2015	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	4	6/9/2015	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2014 ( Subtotal = $405,000 )
2014	2014	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	3	6/17/2014	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2013 ( Subtotal = $375,706 )
2013	2013	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	2	6/28/2013	NON-COMPETING CONTINUATION	$375,706
														Subtotal = $375,706

Issue Date FY: 2012 ( Subtotal = $346,014 )
2012	2012	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	1	7/12/2012	NEW	$346,014
														Subtotal = $346,014

Grand Total All Awards = $6,757,266

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The Impact of Pten Signaling on Neuronal Form and Function

Award Number: R01MH097949

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer