Samie R Jaffrey, MD, PhD

Overview

The Jaffrey lab is interested in identifying RNA regulatory pathways that control protein expression, especially in neurodevelopmental disorders such as mental retardation and autism. We showed that the cause of the abnormal gene silencing that causes the neurodevelopmental disorder Fragile X syndrome involves a novel pathway in which trinucleotide repeat RNA hybridizes to complementary DNA sequences. These studies identified a novel mechanism of epigenetic regulation that may be broadly relevant to repeat expansion disorders. Our work has also elucidated novel RNA-based pathways that underlie axon guidance and circuit formation in the brain, particularly by controlling local translation. We use novel microfluidic techniques to harvest axons for proteomics and molecular biology analysis, which has allowed us to describe some of the first axonally localized mRNAs and their roles in axon guidance and other aspects of neuronal development, including retrograde signaling. These studies have uncovered a striking role for local RNA degradation through the nonsense-mediated RNA decay pathway in shaping the axonal RNA population and regulating local translation.

Our laboratory founded the field of mRNA “epitranscriptomics,” i.e., the study of the role and function of mRNA base modifications. We are particularly interested in the mRNA modification N6-methyladenosine (m6A). Our transcriptome-wide map of m6A was the first global analysis of an mRNA base modification and helped to initiate widespread interest in m6A as a regulatory mechanism for mRNA and ncRNAs. We found that m6A a widespread modification that occurs in over 7000 transcripts in cells. We showed that m6As in mRNAs can markedly enhance mRNA translation and that this mechanism mediates stress-mediated mRNA translation. We also recently showed that numerous mRNAs contain an additional modification near their 5’ caps called N6,2’-O-dimethyladenosine (m6Am). We are determining how m6A, m6Am, and other nucleotide modifications control mRNA and protein expression in diverse cellular and disease contexts.

Highlights

1
Cell · 2020
SRSamie R Jaffrey
PMID: 32492408PMCID: PMC7508256DOISenior author693 citations
2
Cell · 2025
JLJianheng Liu SRSamie R Jaffrey
PMID: 40328256PMCID: PMC12255529DOISenior author42 citations
3
Nature · 2023
SRSamie R Jaffrey
PMID: 36725932PMCID: PMC9891201DOISenior author75 citations

Publications

202

Funding

47 View NIH portfolio on RePORTER ↗

Active

11 grants

PI
Control of gene expression by a metabolite-mRNA interaction network
National Cancer Institute · 2026–2031
R01CA325384-01
PI
Center for Multi-Scale Analysis of the Human Epitranscriptome
National Human Genome Research Institute · 2021–2030· 2 renewals
RM1HG011563-06
PI
Mechanisms of epitranscriptomic regulation in cancer
National Cancer Institute · 2014–2029· 4 renewals
R01CA186702-12
Sub-PI
Molecular mechanisms and functions underlying the role of Fto in mu opioid actions
National Institute on Drug Abuse · 2024–2029 · via Rutgers, The State University of New Jersey – New Brunswick
R01DA059544-03
KP
Synthetic biology in neurons: Chemogenetic control of selective calcium signaling in neurons
National Institute of Neurological Disorders and Stroke · 2026–2028
R21NS142816-01A1
KP
A novel RNA-based neuromodulation tool to treat chronic pain and reduce opioid dependence
National Institute on Drug Abuse · 2026–2028
R21DA066282-01
PI
New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons
National Institute of Neurological Disorders and Stroke · 2019–2027
R35NS111631-08
MPI
Spermatogenic Gene Regulation and Infertility
Eunice Kennedy Shriver National Institute of Child Health and Human Development · 2021–2027 · via Cornell University - Ithaca
P50HD104454-05
PI
MFB: Continuous evolution of RNAs with novel functions in mammalian cells
National Science Foundation · 2024–2027
NSF 2330699
PI
Deciphering the impact of 2'-O-methylation on lung cancer growth and treatment response
Starr Cancer Consortium · 2024–2026
I17-0115
Sub-PI
Fluorescence-based sequence-specific imaging of RNA modifications
National Institute of General Medical Sciences · 2024–2026 · via Mediomics, LLC
R44GM137636-03

Completed grants (36)

MPI
Pho-m6A assay: A phosphoselective method to quantify dynamics of m6A in mRNA
National Institute of Environmental Health Sciences · 2020–2024
R21ES032347-02
PI
The cap epitranscriptome: Regulation of mRNA fate and function by cap-associated methyl modifications
National Institute of Mental Health · 2019–2024
R01MH121072-05
PI
Addgene 766855
Addgene, Inc. · 2023–2024Contract
Addgene 766855
PI
Real-time imaging of metabolic deregulation in cancer
Starr Cancer Consortium · 2019–2023
I12-0051
PI
Addgene 704115
Addgene, Inc. · 2022–2023
Addgene 704115
PI
Addgene 703074
Addgene, Inc. · 2022–2023
Addgene 703074
PI
Post transcriptional regulation of skin stem cells by M6A RNA methylation.
Tri-Institutional Stem Cell Initiative (Weill Cornell) · 2021–2023
2021-010
Co-I
Gene Nutrient Interactions in Kidney Function
National Institute of Diabetes and Digestive and Kidney Diseases · 2017–2022
R01DK113088-01A1
PI
Role of m6A in controlling mRNA fate and function in neurons
National Institute of Neurological Disorders and Stroke · 2012–2022· 2 renewals
R01NS056306-12
PI
Ultra-sensitive multi-mode laser-scanning imaging system
Office of the Director, NIH · 2021–2022
S10OD030335-01
KP
The Role of RNA Methylation in Breast Cancer
U.S. Department of Defense · 2019–2022
No publications yet
W81XWH1910118
PI
Rewiring cellular metabolic networks in diabetes
American Diabetes Association · 2018–2021
1-18-VSN-02
PI
Using Cancer Genome Data to Reveal Regulators of the m6A Epitranscriptome
Memorial Sloan Kettering Cancer Center · 2020–2021Contract
SRA 204351-01
MPI
Uncovering the role of m6A in the melanocyte response to ultraviolet light
National Cancer Institute · 2018–2020
R21CA224391-01A1
PI
The mRNA methylation program in leukemia
Starr Cancer Consortium · 2018–2019
I11-0017
Sub-PI
DNA Helicases as Mediators of Trinucleotide-Repeat Pathology in Fragile X Syndrome
Tri-Institutional Stem Cell Initiative (Weill Cornell) · 2015–2019 · via Yeshiva University
TRI-SCI 2014-15
PI
Platform for rapid discovery of small molecules that bind and modulate ?disease-associated RNA targets
Daedalus Fund for Innovation (Weill Cornell) · 2017–2019
DFI 180147-01
PI
Engineering RNA-Activated Fluorescence Switches for Imaging RNA and RNA Biology
National Institute of Neurological Disorders and Stroke · 2009–2019· 2 renewals
R01NS064516-10
PI
Pathways Controlling mRNA Translation Pathways in Dopaminergic Neurons
National Institute on Drug Abuse · 2014–2019
R01DA037755-05
Sub-PI
Super-Resolution Imaging Via Programmable Autonomous Blinking
National Institute of Biomedical Imaging and Bioengineering · 2013–2018 · via Harvard University
R01EB018659-05
PI
Dissecting mRNA Methylation in Hematopoietic Self-Renewal
Tri-Institutional Stem Cell Initiative (Weill Cornell) · 2016–2018
2016-014
PI
LIPS: A Novel Technology for Spatial and Temporal Control of Protein Synthesis in Dendritic Spines
National Institute of Mental Health · 2015–2018
U01MH109087-03
KP
The mRNA Methylation Program in Leukemia
National Cancer Institute · 2017–2018Fellowship
F32CA221104-01
PI
mRNA Methylation: A Novel Mechanism That Blocks Signaling by Drugs of Abuse
National Institute on Drug Abuse · 2013–2017· 2 renewals
R01DA037150-04S1
Sub-PI
Development of Recombinant Antibodies for Detection of RNA Modifications at Single Nucleotide Resolution
National Institute on Drug Abuse · 2016–2017 · via Mediomics, LLC
R43DA042468-01 EW
PI
Testing the Role of Small RNAs in FMR1 Promoter Silencing in Fragile X Syndrome
National Institute of Neurological Disorders and Stroke · 2014–2016
R21NS087859-02
Sub-PI
Development of RNAs Suitable for Assaying m6A Demethylase Activity
National Institute on Drug Abuse · 2015–2015 · via Base5 Biosciences
R41DA038990-01
PI
Enhancing NAD Delivery to Axons to Mitigate Chemotherapy-Induced Peripheral Neuropathy
National Cancer Institute · 2013–2015
R21CA176638-02
PI
Novel Fluorescent Sensors for Simple, Sensitive, and Specific Protein Detection
National Institute of Biomedical Imaging and Bioengineering · 2009–2014
R01EB010249-05
PI
Role of "Local" MicroRNAs and CGG Repeat-Derived RNAs in Fragile X Syndrome
National Institute of Mental Health · 2007–2012
R01MH080420-05EWO
PI
Comprehensive Profiling of Ubiquitination in Neurons
National Institute of Mental Health · 2009–2011
R21MH086128-02EWO
PI
OptoTFs: Genetically Encoded Light-Activated Transcription Factors
National Institute on Drug Abuse · 2009–2011
RC1DA028556-02EWO
PI
Drug abuse signaling pathways that regulate CREB mRNA translation in dendrites
NIDA · 2007–2010 · via NIH RePORTER
R21DA023581-02
PI
Rapid ligand identification using HIV proteome microarrays
NIAID · 2006–2008 · via NIH RePORTER
R21AI068512-02
PI
Proteome-wide identification of protease targets
NIAID · 2006–2008 · via NIH RePORTER
R21AI068639-02
PI
Detection and characterization of nitric oxide effectors
NIMH · 2002–2008 · via NIH RePORTER
R01MH066204-05

Honors & distinctions

1

Member · American Society for Clinical Investigation · 2017

Available technologies

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Show 5 more technologies

Nicotinamide Riboside for the Prevention and Treatment of Hearing Loss
IssuedPMID 25470550
Platform for Aptamer-Mediated Cellular Regulation using Circular RNA Nanodevices
PCT filedPoC DataPMID 39191249
11080
Synthesis of RNAs Containing Methylated Adenosine Residues and Their Use in Enhancing Translation
IssuedPoC DataPMID 26593424
Tunable Gene Therapy Expression System Regulated by Acyclovir
Application filedPoC DataPMID 41184552
10850
Viral Method to Express Regenerative Proteins in Spinal Cord Injured Axons
IssuedPMID 18193038

News mentions

14 View all WCM news ↗

Dr. Samie Jaffrey Receives NIH Director’s Transformative Research Award
October 6, 2026
Dr. Samie Jaffrey, the Greenberg-Starr Professor in the Department of Pharmacology at Weill Cornell Medicine, has received a five-year, $5.5 million NIH Director’s Transformative Research Award for the comprehensive study of how messenger RNAs are regulated in cells by small molecules called metabolites.
Researchers Unveil a Powerful New Gene-Switch Tool
November 3, 2025
Investigators at Weill Cornell Medicine have developed a versatile and non-toxic technology for controlling the activity of any gene in a cell.
How a Tiny RNA Modification Helps Control Cell Stress Responses
May 5, 2025
A tiny chemical modification commonly found on messenger RNAs plays a surprisingly large role in how cells respond to stress, according to a study led by Weill Cornell Medicine investigators.
NSF Awards Grant for Evolution-inspired Design of Therapeutic RNAs
March 19, 2024
A team led by Dr. Samie Jaffrey, the Greenberg-Starr Professor of Pharmacology at Weill Cornell Medicine, has been awarded a three-year, $1.65 million grant for RNA research under a biotechnology-development program run by the U.S. National Science Foundation.
Discovery Reveals Lipid-Signaling Microdomains in Cells
December 14, 2023
Important signaling molecules called phospholipids are active throughout cells in small compartments called condensates, rather than functioning primarily in cell membranes as previously thought, according to a study from researchers at Weill Cornell Medicine.

Show 9 more mentions

Scientists Shed Light on How Stressed Cells Sequester Protein-Forming mRNAs
September 28, 2023
Researchers at Weill Cornell Medicine have illuminated one of the important ways that cells respond to stress. The findings could also be relevant to Alzheimer’s, ALS and other diseases in which this mechanism may be abnormally active.
DNA Can Fold into Complex Shapes to Execute New Functions
June 21, 2023
DNA can mimic protein functions by folding into elaborate, three-dimensional structures, according to a study from researchers at Weill Cornell Medicine and the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
Scientists Resolve a Long-Standing Mystery About mRNAs
February 1, 2023
Messenger RNAs (mRNAs) contain chemical marks that are critical for antiviral defense in cells.
Dr. Sara Zaccara Honored with 2022 Tri-Institutional Breakout Award
June 6, 2022
Dr. Sara Zaccara, a postdoctoral associate in the Department of Pharmacology at Weill Cornell Medicine, has won a 2022 Tri-Institutional Breakout Award for Junior Investigators.
National Human Genome Research Institute Funds $12.2 Million Center at Weill Cornell Medicine to Study RNA Modifications
November 23, 2021
The National Human Genome Research Institute has funded a multi-institutional Center of Excellence in Genome Sciences (CEGS), based at Weill Cornell Medicine, to develop new tools to study the major product of the human genome, called ribonucleic acid (RNA), and determine how RNA functions to orchestrate the unique patterns of protein expression seen in human tissues and in disease.
Researchers Find that Chemical Marks in Cellular Messages Trigger Their Disposal
June 2, 2020
Three proteins bind to chemical marks on molecular messages in cells, targeting the messages for degradation, according to researchers at Weill Cornell Medicine. The results overturn some prevailing models of how cells use chemical tags to control their genes' expression and may offer new targets for treating leukemia, which can arise when the chemical tags go awry.
Dr. Samie Jaffrey Awarded Prestigious NIH MIRA Grant
October 11, 2019
Dr. Samie R. Jaffrey, the Greenberg-Starr Professor of Pharmacology at Weill Cornell Medicine, has been awarded a Maximizing Investigators’ Research Award (MIRA) from the National Institute of Neurological Disorders and Stroke (NINDS).
Mysterious m6A Marks On RNA Begin To Yield Their Secrets
July 31, 2019
Chemical modifications that appear on some RNA transcripts may have evolved in part to help cells repair themselves after damage, and may also be a key to understanding important human diseases, according to new research from scientists at Weill Cornell Medicine and Cornell’s Ithaca campus.
Circular RNA Could Enable New Therapies, Discoveries
May 22, 2019
A new technique developed by Weill Cornell Medicine investigators that creates an unusually stable form of RNA may illuminate many cellular processes and enable new kinds of gene therapies.

Mentoring

28 All publications with mentees →

9 PhD students · 19 Postdocs

External relationships

Ownership

858 Therapeutics · Chimerna Therapeutics · Lasso Biosciences INC · Lucerna, Inc. · Sensible Biotechnologies INC

Advisory/Scientific Board Member

Lasso Biosciences INC · Sensible Biotechnologies INC

Proprietary Interest

Lucerna, Inc. · Sensible Biotechnologies INC

Other Interest

858 Therapeutics