About

David S. Eisenberg is a Professor of Chemistry and Biochemistry and Biological Chemistry at UCLA, serving as a HHMI Investigator and Director of the UCLA-DOE Institute for Genomics and Proteomics. His educational background includes an A.B. in Biochemical Sciences from Harvard College and a D.Phil. in Theoretical Chemistry from Oxford University, earned on a Rhodes Scholarship. He completed postdoctoral studies at Princeton University, focusing on water and hydrogen bonding, and at Caltech on protein crystallography before joining UCLA's faculty. Eisenberg's research centers on protein interactions, with a particular emphasis on amyloid-forming proteins. His work involves studying the structural basis for the conversion of normal proteins to the amyloid state and the transformation of prions into infectious forms, utilizing techniques such as X-ray crystallography, bioinformatics, and biochemistry. He has contributed significantly to understanding diseases related to protein aggregation, including systemic amyloidosis and neurodegenerative disorders like Alzheimer's, Parkinson's, and ALS. His research has led to the determination of the atomic structure of amyloid fibers and toxic oligomers, providing insights into their stability, formation, and toxicity. Eisenberg has published over 300 papers and reviews, holds multiple patents, and has received numerous awards, including membership in the National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine.

Research topics

• Chemistry
• Medicine
• Biology
• Computational biology
• Environmental science
• Pathology
• Environmental chemistry

Selected publications

• Profile of David Baker, Demis Hassabis, and John Jumper: 2024 Nobel laureates in Chemistry

  Proceedings of the National Academy of Sciences · 2026-02-27

  articleOpen accessSenior author

  The 2024 Nobel Prize in Chemistry recognized revolutionary computational success in predicting protein structures from amino acid sequences and for designing amino acid sequences that fold into desired protein structures. The ultimate accomplishment emerged principally from two labs, applying distinct approaches, culminating four decades of effort by the community of protein scientists. The lab of David Baker at the University of Washington made protein design a reality by adapting methods of classical physical chemistry. Demis Hassabis and John Jumper in the Deep Mind division of Google applied co-evolution and AI methods to enable prediction of protein models remarkably close to experimentally determined structures and prediction of vast numbers of structures of proteins not yet experimentally studied.

  PublisherDOI

• In Vitro and In Vivo Evaluation of Small-Molecule Disassemblers of Pathological Tau Fibrils

  ACS Chemical Neuroscience · 2026-01-05 · 2 citations

  articleSenior authorCorresponding

  Aggregation of the microtubule-binding protein tau is the histopathological hallmark of Alzheimer's disease (AD) and other neurodegenerative diseases, which are collectively known as tauopathies. Tau aggregation in AD patients is correlated with neuron loss, brain atrophy, and cognitive decline, and pro-aggregation tau mutations are sufficient to cause neurodegeneration and dementia in humans and tauopathy model mice. Thus, reversing tau aggregation is a potential therapeutic avenue for AD. In a previous study, we discovered CNS-11, a small molecule that disaggregates AD patient brain-extracted tau fibrils in vitro. In this study, we identify two chemical analogs of CNS-11, named CNS-11D and CNS-11G, that disaggregate AD patient brain-extracted tau fibrils and prevent seeding in a tau aggregation cell culture model. We also demonstrate that 8 weeks of treatment with either CNS-11D or CNS-11G reduces levels of insoluble tau in a mouse model of tauopathy. Our work defines the properties of two small molecules that diminish aggregation of tau in vivo and provides further support for structure-based methods to target tau for treatment of AD.

  PublisherDOI

• CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis

  Cell · 2026-01-28 · 8 citations

  articleOpen access

  controls tau levels in human neurons, ubiquitinates tau, and is correlated with resilience to tauopathies in human disease. Disruption of mitochondrial function promotes proteasomal misprocessing of tau, generating disease-relevant tau proteolytic fragments and changing tau aggregation in vitro. These results systematically reveal principles of tau proteostasis in human neurons and suggest potential therapeutic targets for tauopathies.

  PublisherDOI

• Leveraging structure-informed machine learning for fast steric zipper propensity prediction across whole proteomes

  PLoS Computational Biology · 2025-08-25

  articleOpen accessCorresponding

  Predicting the amyloid fold and the propensity of peptide segments to adopt amyloid-like structures remain a challenge. However, recent progress has facilitated structure-based prediction of steric zipper propensity and the use of machine learning to accelerate the calculation of predictive models across many scientific areas. Leveraging these advances, we have developed a new approach for rapid proteome-wide assessment of zipper profiles that is informed by four million steric zipper predictions collected over ten years. This collection is used to build a machine learning model capable of rapidly predicting steric zipper propensity, and allowing for the assessment of zippers at both the protein and proteome level. Our predictions show enrichment for zipper forming segments in proteins involved in cell wall reorganization in yeast, highlighting a potential category of interest for experimental characterization. Overall, our predictive model allows for the exploration of amyloid formation across the tree of life and provides a tool for assessment of both novel and designed sequences for zipper density.

  PublisherOA PDFDOI

• Efficacy of a synuclein and tau fibril targeting drug in vivo

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: Pre-Fibrillar oligomeric and insoluble fibrillar aggregates of alpha-synuclein (aSyn) accumulate and contribute to the neurodegenerative decline in Parkinson Disease (PD) and other synucleinopathies and frequently occur as co-morbidities in the major tauopathy, Alzheimer Disease (AD). Familial autosomal dominant PD aSyn A53T mutations which promote aggregation cause age-related aSyn and tau pre-fibrillar oligomers and insoluble aSyn fibrillar deposits, neurodegeneration and motor deficits in hemizygous A53T aSyn transgenic mice. METHOD: To test a candidate fibril structure-based therapeutic candidate we treated aSyn deposit-bearing 24 month old heterozygous A53T M83 mice for 6 weeks with a formulation of CNS11g, a small molecule designed to specifically fit an aSyn fibril site required for aggregation and previously demonstrated to disaggregate both pre-existing aSyn and tau fibrils in cell free systems. RESULT: Oral gavage produced brain levels above the in vitro ED50 for disaggregation and ameliorated motor deficits with no evidence of toxicity compared with the vehicle group. CNS11g reduced levels of putatively neurotoxic, SDS-stable, high molecular weight soluble aSyn aggregates detected above 256kD by Western blot analysis in spinal cord and brainstem as well as tau oligomers in spinal cord. Quantitative ICC for p129S aSyn deposits and reactive glia, supported a significant treatment effect, but there was no effect on detergent insoluble p129S aSyn. Our late intervention results provide evidence for effective oral CNS11g delivery, safety and efficacy in reducing motor deficits and soluble p129S aSyn and tau oligomers and aSyn deposits by ICC without biochemical evidence for reducing pre-existing insoluble fibrillar aSyn deposits with this treatment paradigm. CONCLUSION: While higher or longer dosing might disaggregate and clear insoluble fibrils, this initial study suggests oral dosing produces pleiotropic CNS activity against both aSyn and tau pre-fibrillar oligomers implicated in the neurotoxicity, seeding and spreading of two major proteinopathies.

  PublisherOA PDFDOI

• How Sup35 monomer conformation and amyloid fibril polymorphism determine yeast strain phenotypes

  Research Square · 2025-11-03

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Mock fibril structure of CNS-11g

  2025-06-09

  datasetSenior author
  PublisherDOI

• Formation of rippled β-sheets from mixed chirality linear and cyclic peptides—new structural motifs based on the pauling-corey rippled β-sheet

  Chemical Science · 2025-01-01 · 7 citations

  articleOpen access

  The rippled β-sheet is a structural motif formed by certain racemic peptides that is distinct from the commonly known pleated β-sheet. Although the structure was predicted in 1953, unambiguous crystallographic observation of a rippled β-sheet was not reported until 2022. The structural foundation of the rippled β-sheet field continues to expand, stimulating new research questions, both fundamental and applied. Recent studies found that racemic peptides of varied length and amino acid composition assemble into rippled β-sheets. Intriguingly, certain rippled sheets were found to encapsulate small molecules in ways that could become useful in drug delivery, or to trap harmful substances. These and many other potential applications hinge on the development of a comprehensive structural foundation based on both experiment and theory. In this paper we introduce the concept of the single-component rippled-sheet, composed of joined segments of L and D chirality. The scope of rippled sheet-forming motifs is expanded to include two unexplored classes of rippled sheets: single-component cyclic and linear peptide chimeras. We report on the design, synthesis, and crystal structural characterization of eight self-assembling peptide systems. All five linear systems, in which amino acid sequence, charge and chirality were varied, formed rippled β-sheets with distinct two- and three-dimensional lattices. Of the three cyclic peptides, however, only one system formed a rippled β-sheet, while the other two formed pleated β-sheets. Molecular modeling is used to better understand chiral selection in cyclic systems.

  PublisherOA PDFDOI

• CNS-11g reduces α-synuclein pathology and restores motor function in a Parkinson’s model

  Research Square · 2025-11-13

  preprintOpen access
  PublisherOA PDFDOI

• Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein

  npj Parkinson s Disease · 2025-04-23 · 1 citations

  articleOpen accessSenior author

  Aggregation of the protein α-synuclein (α-syn) is the histopathological hallmark of neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Currently, patients with synucleinopathies are diagnosed by physical examination and medical history, often at advanced stages of disease. Because synucleinopathies are associated with α-syn aggregates, and α-syn aggregation often precedes onset of symptoms, detecting α-syn aggregates would be a valuable early diagnostic for patients with synucleinopathies. Here, we design a liganded magnetic nanoparticle (LMNP) functionalized with an α-syn-targeting peptide to be used as a magnetic resonance imaging (MRI)-based biomarker for α-syn. Our LMNPs bind to aggregates of α-syn in vitro, cross the blood-brain barrier in mice with mannitol adjuvant, and can be used as an MRI contrast agent to distinguish mice with α-synucleinopathy from age-matched, wild-type control mice in vivo. These results provide evidence for the potential of magnetic nanoparticles that target α-syn for diagnosis of synucleinopathies.

  PublisherOA PDFDOI

Recent grants

• Reversible Amyloid-Like Fibrils in Membraneless Organelles

  NSF · $829k · 2016–2022

• NIH Grant R01AG029430

  NIH · $3.9M · 2018

• Development of inhibitors for systemic amyloid diseases

  NIH · $1.9M · 2014–2019

• Towards Treatment of Alzheimer’s Disease by Targeting Pathogenic Tau and Beta-Amyloid Structures

  NIH · $1.1M · 2021–2022

• NIH Grant P01NS049134

  NIH · $21.8M · 2016

Frequent coauthors

• M.R. Sawaya

  Howard Hughes Medical Institute

  324 shared

• Duilio Cascio

  University of California, Los Angeles

  158 shared

• David R. Boyer

  University of California, Los Angeles

  81 shared

• José A. Rodríguez

  Universidad de Alcalá

  55 shared

• Tamir Gonen

  University of California, Los Angeles

  49 shared

• Michael P. Hughes

  St. Jude Children's Research Hospital

  47 shared

• Lin Jiang

  Xinjiang Medical University

  44 shared

• Lukasz Goldschmidt

  University of Washington

  43 shared

Awards & honors

• Passano Laureate
• Thomson Reuters Most Highly Cited Author
• Bert and Natalie Vallee Award in Biomedical Science
• UCLA Switzer Prize
• Harvey Prize in Human Health