About

Professor Jean Baum is the Principal Investigator and the Director of the Nuclear Magnetic Resonance Facilities at Rutgers University. Her research interests include collagen-protein interactions and protein aggregation. She leads a research group focused on understanding the molecular mechanisms underlying these biological processes, which are relevant to various health conditions and diseases. Her work involves investigating the structural and dynamic aspects of proteins, including collagen and proteins associated with COVID-19, such as the SARS-CoV-2 spike protein. Through her leadership, the group employs advanced techniques like high-field NMR to explore these complex biological interactions.

Research topics

• Biology
• Computational biology
• Chemistry
• Biochemistry
• Medicine
• Virology
• Genetics
• Biophysics
• Cell biology
• Computational chemistry
• Mathematics
• Immunology

Selected publications

• Differential effects of α-Synuclein monomers and seeds on the material properties of Tau condensates

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-16

  articleOpen access

  Tau and α-Synuclein (αSyn) frequently co-aggregate in various neurodegenerative disorders. Recently, Tau has been shown to form dynamic, liquid-like condensates that can recruit αSyn, and potentially serve as a precursor to pathological aggregation. However, the quantitative impact of αSyn on the material properties of these condensates remains elusive. Here, we measure the viscosity and interfacial tension of Tau condensates and determine how these properties are modulated by αSyn monomers and fibril seeds. We find that while both forms of αSyn partition efficiently into Tau condensates, they exert vastly different effects on the condensate's material state. The viscosity of Tau condensates remains unchanged in the presence of αSyn monomers at concentrations up to 200 μM, accompanied by a moderate reduction in the condensates' interfacial tension. In contrast, the addition of only 5 μM αSyn fibril seeds triggers rapid solidification of Tau condensates, manifested by a nearly 100-fold increase in condensate viscosity within one hour. These findings provide quantitative insights into condensate mechanics, highlighting the unique capacity of αSyn seeds to drive the liquid-to-solid transition of Tau condensates that may underlie the formation of pathological aggregates.

  PublisherDOI

• Biomolecular condensates provide a unique environment for redox-mediated protein crosslinking

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-16

  articleOpen access

  Biomolecular condensates, often formed through liquid-liquid phase separation, are dynamic cellular compartments. Here, we demonstrate that a wide range of fluorescently tagged proteins undergo inadvertent, condensate-mediated crosslinking, resulting in rapid solidification of condensates under common fluorescence imaging conditions. The process is driven by excitation-induced, short-lived reactive oxygen species (ROS), whose otherwise limited crosslinking potential becomes uniquely enabled in the dense phase. In live cells, excitation-induced ROS potently trigger stress granule formation, while the ROS-driven solidification of condensates is modulated by compartment-dependent antioxidant buffering. Our findings demonstrate that condensates create a distinct environment that enables ROS chemistry unlikely to occur in the bulk cytosol. Furthermore, the cellular redox level can be a general regulator of condensate rheology. Beyond biological insights, our findings underscore the need for scrutiny when examining fluorophore-labeled condensates.

  PublisherOA PDFDOI

• Is synuclein aggregation a derived or ancestral trait? Ancestral sequence reconstruction uncovers stepwise evolution of synuclein aggregation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-28

  preprintOpen accessSenior authorCorresponding

  Protein aggregation drives many neurodegenerative diseases, including Parkinson's disease, where misfolded α-synuclein (αSyn) forms fibrillar assemblies that accumulate as Lewy bodies. Although αSyn aggregation has been extensively characterized, its evolutionary origins and sequence determinants remain unresolved. Here, we use ancestral sequence reconstruction (ASR) to trace the emergence of fibril-forming ability in the synuclein family. We inferred synuclein phylogeny and experimentally resurrected common ancestors, including ROOT synuclein, the last common ancestor of all synucleins, and key intermediates along the αSyn lineage. Strikingly, ROOT synuclein is non-aggregating, demonstrating that fibril formation is an evolved, rather than ancestral property. Aggregation first emerges at the ancestral αβ node, is retained in αSyn, and suppressed in β-synuclein. Biophysical analyses including mass spectrometry and NMR reveal that aggregation aligns with greater complexity and heterogeneity in the monomer conformational ensemble, suggesting that evolutionary sequence changes progressively remodel monomer landscapes to favor fibril formation. Complementing these insights, comparative sequence analysis reveals that the transition from ROOT to α-WT is marked by the stepwise acquisition of residues critical for stabilizing the fibril core. Early mutations stabilized the β-arch core, enabling the onset of fibril formation, followed by substitutions that reinforce protofilament-protofilament interactions. Together, ASR defines an evolutionary framework for synuclein aggregation linking progressive sequence evolution and conformational complexity to the molecular origins of αSyn fibril formation.

  PublisherOA PDFDOI

• Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson’s disease

  Cell Reports · 2025-05-01 · 4 citations

  articleOpen access

  Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson's disease (PD). Through a high-throughput screen, we recently identified 38 genes whose knockdown modulates αSyn propagation. Here, we show that, among those, TAX1BP1 regulates how αSyn interacts with lipids, and ADAMTS19 modulates how αSyn phase separates into inclusions, adding to the growing body of evidence implicating those processes in PD. Through RNA sequencing, we identify several genes that are differentially expressed after knockdown of TAX1BP1 or ADAMTS19 and carry an increased frequency of rare risk variants in patients with PD versus healthy controls. Those differentially expressed genes cluster within modules in regions of the brain that develop high degrees of αSyn pathology. We propose a model for the genetic architecture of sporadic PD: increased burden of risk variants across genetic networks dysregulates pathways underlying αSyn homeostasis and leads to pathology and neurodegeneration.

  PublisherDOI

• Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein

  Science Advances · 2025-04-18 · 9 citations

  articleOpen access

  Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a substantial challenge. Here, we develop micropipette aspiration and whole-cell patch-clamp (MAPAC), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify multiple molecular factors that distinctly regulate the viscosity, interfacial tension, and maturation of synapsin condensates, confirming the cellular roles of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo.

  PublisherDOI

• Nanoscale Structural and Functional Impacts of Disease-Associated Collagen Mutations

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-04 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Collagen is the most abundant structural protein in the human body, and its supramolecular organization is central to tissue mechanics and cell-matrix interactions. Integrins, key mediators of these interactions, are essential for key biological processes including adhesion, migration, differentiation, and platelet aggregation. While mutations in collagen are known to cause connective tissue disorders such as Osteogenesis Imperfecta (OI) with phenotypes ranging from mild to perinatal lethal, how these mutations alter fibril level architecture, dynamics and integrin-mediated interactions remains poorly understood. Here, we generated collagen-rich extra-cellular matrix (ECM) from primary dermal fibroblasts of a healthy donor (WT) and from two OI patients carrying distinct glycine mutations: G610C, associated with moderate disease, and G907D, linked to perinatal lethality. Comparative biophysical studies reveal that both mutants retain the canonical D-banding of collagen I fibrils but differ markedly at the nanoscale. G907D fibrils exhibit greater local structural perturbations and increased molecular mobility relative to the non-lethal G610C. Importantly, integrin binding also diverges between mutants: G610C displays reduced affinity, whereas G907D exhibits enhanced affinity compared to WT. Together, these findings establish a mechanistic link between single-residue mutations, nanoscale fibril architecture and collagen-receptor interactions, and highlight how genetic or acquired collagen defects can drive ECM dysregulation.

  PublisherOA PDFDOI

• The material properties and crosstalk between tau and alpha-synuclein condensates

  Biophysical Journal · 2024-02-01

  article
  PublisherDOI

• Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson’s disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-01

  preprintOpen access

  ABSTRACT Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson’s disease and forms intraneuronal inclusions called Lewy Bodies. While the mechanism underlying the dysregulation of αSyn in Parkinson’s disease is unclear, it is thought that prionoid cell-to-cell propagation of αSyn has an important role. Through a high throughput screen, we recently identified 38 genes whose knock down modulates αSyn propagation. Follow up experiments were undertaken for two of those genes, TAX1BP1 and ADAMTS19 , to study the mechanism with which they regulate αSyn homeostasis. We used a recently developed M17D neuroblastoma cell line expressing triple mutant (E35K+E46K+E61K) “3K” αSyn under doxycycline induction. 3K αSyn spontaneously forms inclusions that show ultrastructural similarities to Lewy Bodies. Experiments using that cell line showed that TAX1BP1 and ADAMTS19 regulate how αSyn interacts with lipids and phase separates into inclusions, respectively, adding to the growing body of evidence implicating those processes in Parkinson’s disease. Through RNA sequencing, we identified several genes that are differentially expressed after knock-down of TAX1BP1 or ADAMTS19 . Burden analysis revealed that those differentially expressed genes (DEGs) carry an increased frequency of rare risk variants in Parkinson’s disease patients versus healthy controls, an effect that was independently replicated across two separate cohorts (GP2 and AMP-PD). Weighted gene co-expression network analysis (WGCNA) showed that the DEGs cluster within modules in regions of the brain that develop high degrees of αSyn pathology (basal ganglia, cortex). We propose a novel model for the genetic architecture of sporadic Parkinson’s disease: increased burden of risk variants across genetic networks dysregulates pathways underlying αSyn homeostasis, thereby leading to pathology and neurodegeneration.

  PublisherOA PDFDOI

• Real-time single-molecule observation of incipient collagen fibrillogenesis and remodeling

  Proceedings of the National Academy of Sciences · 2024-08-05 · 9 citations

  articleOpen accessSenior authorCorresponding

  The hierarchic assembly of fibrillar collagen into an extensive and ordered supramolecular protein fibril is critical for extracellular matrix function and tissue mechanics. Despite decades of study, we still know very little about the complex process of fibrillogenesis, particularly at the earliest stages where observation of rapidly forming, nanoscale intermediates challenges the spatial and temporal resolution of most existing microscopy methods. Using video rate scanning atomic force microscopy (VRS-AFM), we can observe details of the first few minutes of collagen fibril formation and growth on a mica surface in solution. A defining feature of fibrillar collagens is a 67-nm periodic banding along the fibril driven by the organized assembly of individual monomers over multiple length scales. VRS-AFM videos show the concurrent growth and maturation of small fibrils from an initial uniform height to structures that display the canonical banding within seconds. Fibrils grow in a primarily unidirectional manner, with frayed ends of the growing tip latching onto adjacent fibrils. We find that, even at extremely early time points, remodeling of growing fibrils proceeds through bird-caging intermediates and propose that these dynamics may provide a pathway to mature hierarchic assembly. VRS-AFM provides a unique glimpse into the early emergence of banding and pathways for remodeling of the supramolecular assembly of collagen during the inception of fibrillogenesis.

  PublisherOA PDFDOI

• Live-Cell Quantification Reveals Viscoelastic Regulation of Synapsin Condensates by α-Synuclein

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-29 · 3 citations

  preprintOpen access

  Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a significant challenge. To address this, we develop MAPAC (micropipette aspiration and whole-cell patch clamp), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify 4 molecular factors that distinctly regulate the viscosity and interfacial tension of synapsin condensates, verifying the cellular effects of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo. .

  PublisherOA PDFDOI

Recent grants

• Integrative NMR and biophysical studies of fibrillar protein assemblies in health and disease

  NIH · $3.3M · 2020–2026

• NIH Grant R29GM045302

  NIH · $628k · 1996

• NIH Grant R01GM087012

  NIH · $607k · 2012

• NMR and biophysical studies of collagen-protein interactions and implications in biological function and disease

  NIH · $5.2M · 1991–2021

• An 800 MHz NMR Cryoprobe for the New Jersey Statewide NMR Facility

  NSF · $191k · 2004–2009

Frequent coauthors

• Helen Berman

  Rutgers, The State University of New Jersey

  50 shared

• Charles L. Brooks

  University of Michigan–Ann Arbor

  49 shared

• Joni Friedman

  University of California, Los Angeles

  49 shared

• Marcella Jackson

  Royal Pavilion

  49 shared

• Janet Kearney

  University of Oxford

  49 shared

• Barry Honig

  Columbia University

  49 shared

• Daniel P. Raleigh

  University College London

  49 shared

• Ex Officio

  John Wiley & Sons (United States)

  49 shared

Labs

• The Baum GroupPI