Uwe Beffert
Research Assistant Professor
Boston University College of Arts and Sciences

PhD, McGill University
BSc, Concordia University

Research Statement:

The Ho-Beffert Lab, led by Dr. Angela Ho and in close collaboration with Dr. Beffert, is dedicated to advancing the understanding of neurological diseases through active genetics and genomics research. Our work has significantly contributed to identifying the role of alternative splicing in Alzheimer's disease (AD) and exploring its functional implications on neuronal receptors.

Key Research Highlights:

1. Alternative Splicing in Alzheimer's Disease: Our recent study involved transcriptomic profiling of aged human postmortem brain samples, uncovering aberrant mRNA splicing events associated with AD. We focused on the apolipoprotein E receptor 2 (APOER2), a receptor interacting with the neuroprotective ligand Reelin and the AD-associated risk factor APOE. Utilizing single-molecule, long-read sequencing, we profiled the entire APOER2 transcript from the parietal cortex and hippocampus of Braak stage IV AD brain tissues along with age-matched controls. Our analysis revealed diverse patterns of cassette exon skipping in APOER2 isoforms, some region-specific or unique to AD-affected brains. Notably, exon 15 of APOER2, encoding the glycosylation domain, showed reduced inclusion in AD brains compared to controls, particularly in the parietal cortex of females with the APOE ?3/?3 genotype. These splicing variations were linked to changes in cell surface expression, APOE-mediated receptor processing, and synaptic number, suggesting a critical role in inducing synaptic alterations and contributing to neuronal dysfunction in AD.

2. Conservation and Divergence of Alternative Splicing Across Species: In another study, we investigated the alternative splicing of Apoer2 across vertebrate species, identifying conserved and divergent splicing events that contribute to functional diversity in the brain. Using single-molecule, long-read RNA sequencing, we profiled full-length Apoer2 isoforms and identified 68 unique isoforms in mice and 48 in humans. We discovered species-specific splicing decisions, such as the tandem skipping of exons encoding protein functional domains in mice, providing new insights into the regulatory mechanisms driving Apoer2 isoform complexity and its functional implications.

Role of apoE-apoER2 interactions in CNS neurons
07/01/2018 - 06/30/2023 (Multi-PI)
NIH/National Institute on Aging

Role of FOXR1 in Mammalian Brain Development
07/01/2015 - 06/30/2018 (Multi-PI)
NIH/National Institute of General Medical Sciences


Yr Title Project-Sub Proj Pubs

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

iCite Analysis       Copy PMIDs To Clipboard

  1. Lagani GD, Lin W, Natarajan S, Lampl N, Harper ER, Emili A, Beffert U, Ho A. Beyond Glycolysis: Aldolase A is a Novel Effector in Reelin Mediated Dendritic Development. bioRxiv. 2024 Jan 12.View Related Profiles. PMID: 38260505; PMCID: PMC10802565; DOI: 10.1101/2024.01.12.575269;
  2. Henry SM, Kistler SA, Lagani GD, Bartling CRO, Özcelik D, Sereikaite V, Strømgaard K, Beffert U, Ho A. Tight control of the APP-Mint1 interaction in regulating amyloid production. Brain Res. 2023 Oct 15; 1817:148496.View Related Profiles. PMID: 37499733; PMCID: PMC10529462; DOI: 10.1016/j.brainres.2023.148496;
  3. Omuro KC, Gallo CM, Scrandis L, Ho A, Beffert U. Human APOER2 Isoforms Have Differential Cleavage Events and Synaptic Properties. J Neurosci. 2022 May 18; 42(20):4054-4068.View Related Profiles. PMID: 35414534; PMCID: PMC9121830; DOI: 10.1523/JNEUROSCI.1800-21.2022;
  4. Gallo CM, Labadorf AT, Ho A, Beffert U. Single molecule, long-read Apoer2 sequencing identifies conserved and species-specific splicing patterns. Genomics. 2022 Mar; 114(2):110318.View Related Profiles. PMID: 35192893; PMCID: PMC8978334; DOI: 10.1016/j.ygeno.2022.110318;
  5. Mota A, Waxman HK, Hong R, Lagani GD, Niu SY, Bertherat FL, Wolfe L, Malicdan CM, Markello TC, Adams DR, Gahl WA, Cheng CS, Beffert U, Ho A. FOXR1 regulates stress response pathways and is necessary for proper brain development. PLoS Genet. 2021 11; 17(11):e1009854.View Related Profiles. PMID: 34723967; PMCID: PMC8559929; DOI: 10.1371/journal.pgen.1009854;
  6. Gallo CM, Ho A, Beffert U. ApoER2: Functional Tuning Through Splicing. Front Mol Neurosci. 2020; 13:144.View Related Profiles. PMID: 32848602; PMCID: PMC7410921; DOI: 10.3389/fnmol.2020.00144;
  7. Lin AY, Henry S, Reissner C, Neupert C, Kenny C, Missler M, Beffert U, Ho A. A rare autism-associated MINT2/APBA2 mutation disrupts neurexin trafficking and synaptic function. Sci Rep. 2019 04 15; 9(1):6024.View Related Profiles. PMID: 30988517; PMCID: PMC6465354; DOI: 10.1038/s41598-019-42635-7;
  8. Dillon GM, Tyler WA, Omuro KC, Kambouris J, Tyminski C, Henry S, Haydar TF, Beffert U, Ho A. CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development. Neuron. 2017 Mar 22; 93(6):1344-1358.e5.View Related Profiles. PMID: 28285824; PMCID: PMC5405870; DOI: 10.1016/j.neuron.2017.02.039;
  9. Wasser CR, Masiulis I, Durakoglugil MS, Lane-Donovan C, Xian X, Beffert U, Agarwala A, Hammer RE, Herz J. Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning. Sci Signal. 2014 Nov 25; 7(353):ra113. PMID: 25429077; PMCID: PMC4355955; DOI: 10.1126/scisignal.2005438;
  10. Beffert U, Dillon GM, Sullivan JM, Stuart CE, Gilbert JP, Kambouris JA, Ho A. Microtubule plus-end tracking protein CLASP2 regulates neuronal polarity and synaptic function. J Neurosci. 2012 Oct 03; 32(40):13906-16.View Related Profiles. PMID: 23035100; PMCID: PMC3489028; DOI: 10.1523/JNEUROSCI.2108-12.2012;
Showing 10 of 41 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 41 publications over 22 distinct years, with a maximum of 5 publications in 1999


Contact for Mentoring:

24 Cummington Mall, Rm. 506
Boston MA 02215
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617-353-6340 (fax)

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