Overview
We currently work on a number of topics centered around RNA isoform biology.
1. Developing a complete isoform view of biology
It is well established that the vast majority of mammalian genes can generate multiple isoforms. Yet, the majority of publications considers a "one-gene-one-protein" model, in which each gene's expression is represented by a single number. If we take the view that genes can talk - the "one-gene-one-number" approach is akin to judging each gene by how much it talks; not by what it is actually saying. To overcome these shortcomings, we engage in tech-development efforts.
Please see
https://www.nature.com/articles/nbt.4259
https://www.nature.com/articles/nbt.3242
https://www.pnas.org/content/111/27/9869.long
https://www.nature.com/articles/nbt.2705
2. Isoform usage patterns in the central nervous system
All cells in a mammalian brain have (approximately) the same genome - yet they have unique ways of interpreting this genome by producing characteristic expression patterns of genes - and unique sets of RNA and protein isoforms. We aim at finding these characteristic isoforms of a variety of cell types and establish if and how they are linked to the cell's function.
Please see
https://www.nature.com/articles/nbt.4259
https://www.nature.com/articles/nbt.3242
3. Isoform switches associated with development & aging
Complex organs such as the brain change dramatically first during development and then again during the aging process - despite only relatively small changes in DNA sequence. We aim at using our unique set of technological insights to understand how isoform usage is affected, both during development and aging - and at distinguishing causes from consequences.
https://www.biorxiv.org/content/10.1101/2020.08.27.268730v1
4. Isoform usage in developmental disorders and neurodegenerative disease
Both developmental and neurodegenerative diseases have devastating consequences for the affected individuals. Yet a true isoform view of these diseases is lacking in almost all cases and may advance our understanding of the molecular causes for disease
Highlights
- 1Nature neuroscience · 2024
- 2Nature biotechnology · 2023
- 3Nature biotechnology · 2022
Publications
Funding
Active
6 grants- PIR35GM152101-03Multiome measurements connecting transcription start sites at single-nucleotide resolution, DNA methylation and open chromatin status to splicing outcome across single cells in health and diseaseNational Institute of General Medical Sciences · 2024–2029
- PICAF 255586-01Comparison of cell-autonomous and cell-non-autonomous effects of Aß and tau aggregates and microglial CD33-isoforms between entorhinal cortex and hippocampusCure Alzheimer’s Fund · 2026–2028
- Co-IP50AR070594-06Center for Lupus ResearchNational Inst of Arthritis & Musculoskeletal & Skin Diseases · 2022–2027
- PICAF 252923-02A three-dimensional tissue model linking tau tangles, abeta and microglial CD33-isoform state to gene- and isoform-expression dysregulation.Cure Alzheimer’s Fund · 2025–2027
- MPIU01DA053625-03S1Integrative Single Cell isoform and chromatin accessibility Mapping of Chronic Opioid Exposure in Cognitive Brain Areas in HIVNational Institute on Drug Abuse · 2021–2027· 2 renewals
- Co-IR01HL136520-05A1Contribution of G Protein Coupled Estrogen Receptor to Changes in Hypothalamic Plasticity and Hypertension Susceptibility in Mice with Accelerated Ovarian FailureNational Heart, Lung, and Blood Institute · 2023–2026
Completed grants (4)
- Co-IR01CA249054-02Clinical and Molecular Heterogeneity in the Myelodysplastic SyndromesNational Cancer Institute · 2020–2025 · via New York University Medical Center
- PIR01GM135247-02Cross-species conservation of cell-type and single-cell specific isoform expressionNational Institute of General Medical Sciences · 2020–2024· 3 renewals
- PIRF1MH121267-01Single cell isoform expression across mouse brain regions and developmentNational Institute of Mental Health · 2019–2023
- PISRA 201550-01CERA Collaboration AgreementCENTRE FOR EYE RESEARCH AUSTRALIA LTD · 2019–2020Contract
News mentions
- New Atlas of mRNA Variants Captures Inner Workings of the BrainApril 9, 2024
Investigators at Weill Cornell Medicine have assembled the most comprehensive atlas to date of messenger RNA (mRNA) variants in the mouse and human brain, which will be important in understanding brain development, neuron specialization and other brain functions.
Mentoring
- NBNatan BelchikovPhysiology, Biophysics & Systems Biology (PhD) · Class of 2026
- CFCareen FoordNeuroscience (PhD) · Class of 2025
- AJAnoushka JoglekarTri-I Program in Computational Biology & Medicine · Class of 2022
External relationships
Advisory/Scientific Board Member
University of Lisbon
Speaker/Lecturer
Agency for Science, Technology and Research (A*STAR) · Broad Institute Inc · Centre de Regulacio Genomica (Centre for Genomic Regulation) · Fondazione Human Technopole d/b/a Human Technopole · Francis Crick Institute Limited · German Cancer Research Center · Karolinska Institutet · Leiden University Medical Center · Max Delbrueck Center for Molecular Medicine · Max Planck Institute of Molecular Cell Biology and Genetics · Northwestern University Feinberg School of Medicine · NOVA University Lisbon (Universidade Nova de Lisboa) · Pacific Biosciences · Paris Brain Institute (Institut du Cerveau et de la Moelle Epiniere) · Rutgers, The State University of New Jersey – New Brunswick · Stanford University · Universitat de València (University of Valencia) · University of Basel · University of California, Santa Cruz · University of Helsinki · University of Miami · University of Michigan · University of Oxford · Yale University
Other
eGenesis · ISOgenix Limited