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New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons

Award Number: R35NS111631
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons - The overall goal of our research program is to understand the intricate mechanisms by which neurons establish the precise spatial and patterns of protein synthesis needed for synaptic plasticity and circuit formation. Much of this regulation occurs at the RNA level, and my laboratory focuses on uncovering novel regulatory mechanisms that enable this RNA-based control. Our research centers around three programs: (1) Epitranscriptomic regulation of neuronal mRNAs. We are often credited with helping to start a new field of RNA biology termed “epitranscriptomics,” the idea that mRNA fate and function is encoded in the RNA by regulatory nucleotide modifications. A major program in my lab focuses on epitranscriptomic regulation of mRNA fate in neurons by these modifications. (2) Deciphering the mechanism of RNA-directed epigenetic silencing in fragile X syndrome. We recently showed that fragile X syndrome is a disease caused by CGG repeat RNA. We found that this RNA forms a hybrid with complementary DNA to induce the epigenetic silencing, which constitutes a new epigenetic pathway. We are committed to understanding this new area of epigenetics and using knowledge of this pathway to develop a completely new approach to treat this major neurological condition. (3) Technologies for revealing the function of the synaptic transcriptome. In order to reveal new insights into RNA regulation in the brain, we develop novel technologies to enable imaging and analysis of mRNA, perhaps most notably “RNA mimics of GFP,” including Spinach. We will take these fluorogenic aptamers to the next level of brightness needed for the demanding imaging approaches used in live functioning animals. Additionally, we will be developing new engineered aptamers that enable light-control of synaptic mRNA translation. Overall, this research program will advance our understanding of post- transcriptional gene regulation in neurons.


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 = $1,084,800 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	5/30/2025	NON-COMPETING CONTINUATION	$1,084,800
														Subtotal = $1,084,800

Issue Date FY: 2024 ( Subtotal = $1,052,256 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	5/22/2024	NON-COMPETING CONTINUATION	$1,052,256
														Subtotal = $1,052,256

Issue Date FY: 2023 ( Subtotal = $1,084,800 )
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/12/2023	NON-COMPETING CONTINUATION	$1,084,800
														Subtotal = $1,084,800

Issue Date FY: 2022 ( Subtotal = $1,084,800 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/23/2022	NON-COMPETING CONTINUATION	$1,084,800
														Subtotal = $1,084,800

Issue Date FY: 2021 ( Subtotal = $1,084,800 )
2021	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/21/2021	NON-COMPETING CONTINUATION	$1,084,800
														Subtotal = $1,084,800

Issue Date FY: 2020 ( Subtotal = $1,084,800 )
2020	2020	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/20/2020	NON-COMPETING CONTINUATION	$1,084,800
														Subtotal = $1,084,800

Issue Date FY: 2019 ( Subtotal = $1,040,005 )
2019	2019	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/1/2019	NEW	$1,040,005
														Subtotal = $1,040,005

Grand Total All Awards = $7,516,261

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New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons

Award Number: R35NS111631

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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