Suman De

Neuroscience, School of Medicine and Population Health

Research Fellow

UKRI Future Leaders Fellow

s.de@sheffield.ac.uk
+44 114 21 59107

Sheffield Institute for Translational Neuroscience (SITraN)

Full contact details

Suman De
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ

Research interests

Identification and characterisation of protein complexes, aggregates and post-translational modifications in human is essential for understanding the underlying mechanism of a range of neurodegenerative disease including Alzheimer’s disease, Parkinson disease and Amyotrophic Lateral Sclerosis. In all these diseases, physiological form of proteins such as amyloid-β, α-synuclein, Tar DNA binding protein-43, under specific conditions, aggregate into a range of soluble complexes, and ultimately polymerising into insoluble fibrils to deposit in the specific parts of the central nervous system. These diseases associated proteins can potentially aggregate into many different forms, consisting of different numbers of peptides, with multiple possible post-translational modifications and co-aggregating species. Since the structural and compositional heterogeneities of these protein aggregate correlate with the disease type and severity, determination of specific molecular details of individual pathogenic aggregates is of vital importance.

In our group, we develop and apply novel imaging-based biophysical methodologies to identify and characterise these disease-associated protein aggregates at the single-molecule level with the goal of identifying the structural determinants of their pathogenicity, determining the primary molecular events that trigger their formation and finally, finding the right molecular approach to prevent their formation, block their neurotoxic effects or enhance their clearance. Single-molecule characterisation of these individual aggregates is crucial, especially in a scenario where toxicity may arise from a specific type of species, conformation, or pathways. By studying aggregation and propagation of disease-relevant proteins at the highest level of sensitivity, we aim to understand molecular mechanism underpinning various neurological disorders such as Alzheimer’s disease, Parkinson disease and Amyotrophic Lateral Sclerosis.

Current ProjectS

Interaction of Amyloid-β and Apolipoprotein in Alzhimer’s disease
Protein-aggregate membrane interaction in health and disease
Misfolded and aggregated conformational strains in Neurodegenerative Diseases
Identificaton and charecterisation of protein aggregates in human biofluids and post-mortem tissue

Publications

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All publications

Journal articles

Bell SM, Wareing H, Hamshaw A, De S, New E, Shaw P, De Marco M, Venneri A, Blackburn DJ, Ferraiuolo L & Mortiboys H (2023) Deficits in mitochondrial function and glucose metabolism seen in sporadic and familial Alzheimer’s disease derived Astrocytes are ameliorated by increasing hexokinase 1. Alzheimer's & Dementia, 19(S13).
Emin D, Zhang YP, Lobanova E, Miller A, Li X, Xia Z, Dakin H, Sideris DI, Lam JYL, Ranasinghe RT , Kouli A et al (2022) Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease. Nature Communications, 13(1).
Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova EI, Berezhnov AV, De S, Peddie CJ, Athauda D , Virdi GS et al (2022) Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity. Nature Neuroscience, 25(9), 1134-1148.
Meng JX, Zhang Y, Saman D, Haider AM, De S, Sang JC, Brown K, Jiang K, Humphrey J, Julian L , Hidari E et al (2022) Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.. Nature Communications, 13.
Sideris DI, Danial JSH, Emin D, Ruggeri FS, Xia Z, Zhang YP, Lobanova E, Dakin H, De S, Miller A , Sang JC et al (2021) Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer’s disease. Brain Communications, 3(3).
Vilalta A, Zhou Y, Sevalle J, Griffin JK, Satoh K, Allendorf DH, De S, Puigdellívol M, Bruzas A, Burguillos MA , Dodd RB et al (2021) Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation. Journal of Biological Chemistry, 296, 100631-100631.
Flagmeier P, De S, Michaels TCT, Yang X, Dear AJ, Emanuelsson C, Vendruscolo M, Linse S, Klenerman D, Knowles TPJ & Dobson CM (2020) Direct measurement of lipid membrane disruption connects kinetics and toxicity of Aβ42 aggregation. Nature Structural & Molecular Biology, 27(-), 886-891. View this article in WRRO
Whiten DR, Brownjohn PW, Moore S, De S, Strano A, Zuo Y, Haneklaus M, Klenerman D & Livesey FJ (2020) TNF induces increased production of extracellular amyloid-β- and α-synuclein-containing aggregates by human Alzheimer’s disease neurons. Brain Communications. View this article in WRRO
Angelova PR, Choi ML, Berezhnov AV, Horrocks MH, Hughes CD, De S, Rodrigues M, Yapom R, Little D, Dolt KS , Kunath T et al (2020) Correction: Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Cell Death & Differentiation, 27(9), 2747-2747.
Angelova PR, Choi ML, Berezhnov AV, Horrocks MH, Hughes CD, De S, Rodrigues M, Yapom R, Little D, Dolt KS , Kunath T et al (2020) Alpha synuclein aggregation drives ferroptosis : an interplay of iron, calcium and lipid peroxidation. Cell Death & Differentiation. View this article in WRRO
Sanderson JB, De S, Jiang H, Rovere M, Jin M, Zaccagnini L, Hays Watson A, De Boni L, Lagomarsino VN, Young-Pearse TL , Liu X et al (2020) Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies. Brain Communications, 2(1). View this article in WRRO
Choi ML, Horrocks MH, Rodrigues M, De S, Tosatto L, Zhang W, Virdi G, Klenerman D, Abramov AY & Gandhi S (2020) Tracking Oligomerization of Alpha-Synuclein Demonstrates Pivotal Role of Mitochondria in Seeding. Biophysical Journal, 118(3), 217a-217a.
De S & Klenerman D (2019) Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1867(10), 870-878. View this article in WRRO
De S, Whiten DR, Ruggeri FS, Hughes C, Rodrigues M, Sideris DI, Taylor CG, Aprile FA, Muyldermans S, Knowles TPJ , Vendruscolo M et al (2019) Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression. Acta Neuropathologica Communications, 7(1). View this article in WRRO
De S, Whiten DR, Hughes C & Klenerman D (2019) O3-01-03: MECHANISM OF TOXICITY INDUCED BY AMYLOID-BETA AGGREGATES CHANGES DURING THE PROGRESSION OF ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 15, P875-P876.
Weiffert T, Meisl G, Flagmeier P, De S, Dunning CJR, Frohm B, Zetterberg H, Blennow K, Portelius E, Klenerman D , Dobson CM et al (2019) Increased Secondary Nucleation Underlies Accelerated Aggregation of the Four-Residue N-Terminally Truncated Aβ42 Species Aβ5–42. ACS Chemical Neuroscience, 10(5), 2374-2384.
Sang JC, Lee J-E, Dear AJ, De S, Meisl G, Thackray AM, Bujdoso R, Knowles TPJ & Klenerman D (2019) Direct observation of prion protein oligomer formation reveals an aggregation mechanism with multiple conformationally distinct species. Chemical Science, 10(17), 4588-4597. View this article in WRRO
De S, Wirthensohn DC, Flagmeier P, Hughes C, Aprile FA, Ruggeri FS, Whiten DR, Emin D, Xia Z, Varela JA , Sormanni P et al (2019) Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms. Nature Communications, 10(1), ---. View this article in WRRO
Lee J-E, Sang JC, Rodrigues M, Carr AR, Horrocks MH, De S, Bongiovanni MN, Flagmeier P, Dobson CM, Wales DJ , Lee SF et al (2018) Mapping surface hydrophobicity of α-synuclein oligomers at the nanoscale. Nano Letters, 18(12), 7494-7501. View this article in WRRO
Iljina M, Dear AJ, Garcia GA, De S, Tosatto L, Flagmeier P, Whiten DR, Michaels TCT, Frenkel D, Dobson CM , Knowles TPJ et al (2018) Quantifying co-oligomer formation by α-synuclein. ACS Nano, 12(11), 10855-10866. View this article in WRRO
Whiten DR, Zuo Y, Calo L, Choi M-L, De S, Flagmeier P, Wirthensohn DC, Kundel F, Ranasinghe RT, Sanchez SE , Athauda D et al (2018) Nanoscopic characterisation of individual endogenous protein aggregates in human neuronal cells. ChemBioChem, 19(19), 2033-2038. View this article in WRRO
Whiten DR, Zuo Y, Calo L, Choi M-L, De S, Flagmeier P, Wirthensohn DC, Kundel F, Ranasinghe RT, Sanchez SE , Athauda D et al (2018) Cover Feature: Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells (ChemBioChem 19/2018). ChemBioChem, 19(19), 2001-2001.
Whiten DR, Cox D, Horrocks MH, Taylor CG, De S, Flagmeier P, Tosatto L, Kumita JR, Ecroyd H, Dobson CM , Klenerman D et al (2018) Single-molecule characterization of the interactions between extracellular chaperones and toxic α-synuclein oligomers. Cell Reports, 23(12), 3492-3500. View this article in WRRO
Varela JA, Rodrigues M, De S, Flagmeier P, Gandhi S, Dobson CM, Klenerman D & Lee SF (2018) Optical structural analysis of individual α-synuclein oligomers. Angewandte Chemie International Edition, 57(18), 4886-4890. View this article in WRRO
Varela JA, Rodrigues M, De S, Flagmeier P, Gandhi S, Dobson CM, Klenerman D & Lee SF (2018) Optical Structural Analysis of Individual α-Synuclein Oligomers. Angewandte Chemie, 130(18), 4980-4984.
Kundel F, De S, Flagmeier P, Horrocks MH, Kjaergaard M, Shammas SL, Jackson SE, Dobson CM & Klenerman D (2018) Hsp70 inhibits the nucleation and elongation of tau and sequesters tau aggregates with high affinity. ACS Chemical Biology, 13(3), 636-646. View this article in WRRO
De S & Klenerman D (2018) O1‐01‐01: CHARACTERIZING PROTEIN AGGREGATES FROM THE HUMAN BRAIN. Alzheimer's & Dementia, 14(7S_Part_3).
Whiten DR, Brownjohn PW, Moore S, De S, Zuo Y, Livesey R & Klenerman D (2018) P2‐176: PROTEIN AGGREGATION AND NEUROINFLAMMATION ARE INTERRELATED IN ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 14(7S_Part_13).
Drews A, De S, Flagmeier P, Wirthensohn DC, Chen W-H, Whiten DR, Rodrigues M, Vincke C, Muyldermans S, Paterson RW , Slattery CF et al (2017) Inhibiting the Ca 2+ influx induced by human CSF. Cell Reports, 21(11), 3310-3316. View this article in WRRO
Schellhaus AK, Moreno-Andrés D, Chugh M, Yokoyama H, Moschopoulou A, De S, Bono F, Hipp K, Schäffer E & Antonin W (2017) Developmentally regulated GTP binding protein 1 (DRG1) controls microtubule dynamics. Scientific Reports, 7(1). View this article in WRRO
De S (2017) [P3-074]: AN ULTRA-SENSITIVE ASSAY TO MEASURE AGGREGATE INDUCED CA2+ INFLUX IN HUMAN CEREBROSPINAL FLUID. Alzheimer's & Dementia, 13(7S_Part_20), P960-P960.
Flagmeier P, De S, Wirthensohn DC, Lee SF, Vincke C, Muyldermans S, Knowles TPJ, Gandhi S, Dobson CM & Klenerman D (2017) Ultrasensitive Measurement of Ca2+ Influx into Lipid Vesicles Induced by Protein Aggregates. Angewandte Chemie, 129(27), 7858-7862.
Flagmeier P, De S, Wirthensohn DC, Lee SF, Vincke C, Muyldermans S, Knowles TPJ, Gandhi S, Dobson CM & Klenerman D (2017) Ultrasensitive measurement of Ca2+ influx into lipid vesicles induced by protein aggregates. Angewandte Chemie International Edition, 56(27), 7750-7754. View this article in WRRO
Irfanullah M, Sharma DK, Chulliyil R, Layek A, De S & Chowdhury A (2017) Heterogeneity in optical properties of near white-light emissive europium complex species revealed by spectroscopy of single nanoaggregates. Chemical Physics Letters, 667, 247-253.
Bhattacharya S, Sharma DK, De S, Mahato J & Chowdhury A (2016) Heterogeneity during Plasticization of Poly(vinylpyrrolidone): Insights from Reorientational Mobility of Single Fluorescent Probes. The Journal of Physical Chemistry B, 120(48), 12404-12415.
Bhattacharya S, Dey A & Chowdhury A (2014) Probing Differential Hydration of Poly(vinylpyrrolidone) Thin Films Using Tracer Mobility: An Insight from Fluorescence Correlation Spectroscopy. The Journal of Physical Chemistry B, 118(19), 5240-5249.
Bhattacharya S, Sharma DK, Saurabh S, De S, Sain A, Nandi A & Chowdhury A (2013) Plasticization of Poly(vinylpyrrolidone) Thin Films under Ambient Humidity: Insight from Single-Molecule Tracer Diffusion Dynamics. The Journal of Physical Chemistry B, 117(25), 7771-7782.
De S, Layek A, Bhattacharya S, Kumar Das D, Kadir A, Bhattacharya A, Dhar S & Chowdhury A (2012) Quantum-confined stark effect in localized luminescent centers within InGaN/GaN quantum-well based light emitting diodes. Applied Physics Letters, 101(12), 121919-121919.
De S, Kumar Das D, Layek A, Raja A, Kumar Singh M, Bhattacharya A, Dhar S & Chowdhury A (2011) Optoelectronic behaviors and carrier dynamics of individual localized luminescent centers in InGaN quantum-well light emitting diodes. Applied Physics Letters, 99(25), 251911-251911.
De S, Layek A, Raja A, Kadir A, Gokhale MR, Bhattacharya A, Dhar S & Chowdhury A (2011) Two Distinct Origins of Highly Localized Luminescent Centers within InGaN/GaN Quantum-Well Light-Emitting Diodes. Advanced Functional Materials, 21(20), 3828-3835.
De S, Layek A, Raja A, Kadir A, Gokhale MR, Bhattacharya A, Dhar S & Chowdhury A (2011) Light-Emitting Diodes: Two Distinct Origins of Highly Localized Luminescent Centers within InGaN/GaN Quantum-Well Light-Emitting Diodes (Adv. Funct. Mater. 20/2011). Advanced Functional Materials, 21(20), 3827-3827.
Ghosh A, Bhasker HP, Mukherjee A, Kundu T, Singh BP, Dhar S, De S & Chowdhury A (2011) Polarity selective etching: A self-assisted route for fabricating high density of c-axis oriented tapered GaN nanopillars. Journal of Applied Physics, 110(3), 033528-033528.
Layek A, De S, Thorat R & Chowdhury A (2011) Spectrally Resolved Photoluminescence Imaging of ZnO Nanocrystals at Single-Particle Levels. The Journal of Physical Chemistry Letters, 2(11), 1241-1247.
Bell SM, Wareing H, Capriglia F, Hughes R, Barnes K, Hamshaw A, Adair L, Shaw A, Olejnik A, De S , New E et al () Increasing hexokinase 1 expression improves mitochondrial and glycolytic functional deficits seen in sporadic Alzheimer’s disease astrocytes. Molecular Psychiatry.
De S () Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease. Nature Communications.
Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova EI, Berezhnov AV, De S, Peddie CJ, Athauda D , Virdi GS et al () Author Correction: Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity. Nature Neuroscience.
Rodrigues M, Bhattacharjee P, Brinkmalm A, Do DT, Pearson CM, De S, Ponjavic A, Varela JA, Kulenkampff K, Baudrexel I , Emin D et al () Structure-specific amyloid precipitation in biofluids. Nature Chemistry.
Vilalta A, Zhou Y, Sevalle J, Griffin JK, Satoh K, Allendorf DH, De S, Puigdellívol M, Bruzas A, Burguillos MA , Dodd RB et al () Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, while the Alzheimer’s R47H mutant does the opposite.
Angelova PR, Choi ML, Berezhnov AV, Horrocks MH, Hughes CD, De S, Rodrigues M, Yapom R, Little D, Dolt KS , Kunath T et al () Correction: Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Cell Death & Differentiation.
Sharma DK, Irfanullah M, Basu SK, Madhu S, De S, Jadhav S, Ravikanth M & Chowdhury A () An approach to estimate spatial distribution of analyte within cells using spectrally-resolved fluorescence microscopy. Methods and Applications in Fluorescence, 5(1), 014003-014003.
Hazarika A, Layek A, De S, Nag A, Debnath S, Mahadevan P, Chowdhury A & Sarma DD () Ultranarrow and Widely TunableMn2+-Induced Photoluminescence from Single Mn-Doped Nanocrystals of ZnS-CdS Alloys. Physical Review Letters, 110(26).
De S, Jannasch A, Szilagyi SA, Burmeister M, Davis T, Hermsdorf GL & Schäffer E () Fast 3D imaging of giant unilamellar vesicles using re ected light-sheet microscopy with single molecule sensitivity. Journal of Microscopy.

Chapters

Jannasch A, Abdosamadi MK, Ramaiya A, De S, Ferro V, Sonnberger A & Schäffer E (2017) Custom-Made Microspheres for Optical Tweezers, Optical Tweezers (pp. 137-155). Springer New York

Preprints

Urbanek A, Garland EF, Prescott EE, King MC, Olerinyova A, Wareing HE, Georgieva N, Bradshaw EL, Tzokov SB, Knight A , Tartakovskii AI et al (2024) Molecular determinants of protein pathogenicity at the single-aggregate level, Cold Spring Harbor Laboratory.
Bell SM, Wareing H, Hamshaw A, De S, New E, Shaw PJ, De Marco M, Venneri A, Blackburn DJ, Ferraiuolo L & Mortiboys H (2023) Deficits in mitochondrial function and glucose metabolism seen in sporadic and familial Alzheimer’s disease derived Astrocytes are ameliorated by increasing hexokinase 1 expression, Cold Spring Harbor Laboratory.
Xia Z, Prescott E, Wareing H, Matuszyk M, Dakin H, Dimou E, Hidari E, Zhang Y, Lam J, Danial J , Leah T et al (2022) Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease, Research Square Platform LLC.
Hazarika A, Layek A, De S, Nag A, Debnath S, Mahadevan P, Chowdhury A & Sarma DD (2013) Ultra-narrow and widely tunable Mn^(2+) Emission from Single Nanocrystals of ZnS-CdS alloy, arXiv.
Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova E, Berezhnov A, De S, Peddie C, Athauda D , Virdi GS et al () Structural conversion of α-synuclein at the mitochondria induces neuronal toxicity, Cold Spring Harbor Laboratory.
Xia Z, Prescott E, Leah T, Dakin H, Dimou E, Zuo E, Zhang YP, Lam JYL, Danial JSH, Jiang H , Mortiboys H et al () Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease, Cold Spring Harbor Laboratory.
Klenerman D, Meng J, Zhang Y, Saman D, De S, Sang J, Jiang K, Humphrey J, Julian L, Hidari E , Floto RA et al () Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent inflammatory responses, Research Square Platform LLC.
Rodrigues M, Bhattacharjee P, Brinkmalm A, Do D, Pearson C, De S, Ponjavic A, Varela J, Ruggeri F, Baudrexel I , Lee J et al () Amyloid precipitation in biofluids using a structure-specific chemical antibody, Research Square Platform LLC.
Szilagyi SA, Burmeister M, Davis QT, Hermsdorf GL, De S, Schäffer E & Jannasch A () Fast 3D imaging of giant unilamellar vesicles using reflected light-sheet microscopy with single molecule sensitivity, Cold Spring Harbor Laboratory.
De S, Whiten DR, Ruggeri FS, Hughes C, Rodrigues M, Sideris DI, Taylor CG, Aprile FA, Muyldermans S, Knowles TPJ , Vendruscolo M et al () ADSoluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression, Cold Spring Harbor Laboratory.

Grants

2022-2026: UKRI Future Leaders Fellowship

2021-2023: AMS Springboard Award

2019: Pilot Grant funded by Dementia Research Institute UK

2019: Pilot Grant funded Alzheimer’s Research UK

2016: Marie Curie Individual Fellowship funded by European Union

School of Medicine and Population Health