Ashim Paul, Ph.D

Senior Scientist
Structural Biology & Bioinformatics
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Research Focus

Welcome to our laboratory, where we delve into the intricacies of protein-misfolding diseases. Our primary focus is on unraveling the molecular mechanisms that underlie protein aggregation in neurodegenerative conditions such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis diseases. We employ a multifaceted approach, examining these diseases through the frameworks of Protein-Protein Interactions (PPIs), Protein-Lipid Interactions (PLIs), and Post-Translational Modifications (PTMs). In addition, our work extends to investigating the accumulation of metabolites associated with inborn errors of metabolism, specifically lysosomal storage disorders. We are particularly interested in understanding how these metabolic errors interact with neurodegenerative diseases, exploring avenues for potential cross-talk between these distinct yet interrelated conditions. Our multidisciplinary approach brings together expertise in various fields including peptide chemistry, experimental biophysics, molecular biology, neuroscience, and materials science. We adopt a diverse array of state-of-the-art techniques such as mass spectrometry, fluorescence spectroscopy, circular dichroism, Nuclear Magnetic Resonance, Fourier-Transform Infrared Spectroscopy, molecular docking studies, X-ray crystallography, and various forms of electron microscopy. We invite you to explore our research and join us in our endeavor to comprehend and combat protein-misfolding diseases.

Research Interest

  • Understanding molecular mechanisms, of protein aggregation in Neurodegenerative diseases (Alzheimer’s, Parkinson’s and ALS diseases) and of metabolite assemblies associated in inborn errors of metabolism, specifically lysosomal storage disorders (Gaucher’s and Krabbe disease). 
  • Diagnostic and therapeutic development towards Neurodegenerative and metabolic diseases.
  • Protein-protein and protein-lipid interactions. 
  • Structural investigation of protein and lipid assemblies using different analytical tools, including NMR, CD, FTIR, XRD and Electron microscopies. 
  • Protein & peptide chemistry(solution and solid phase peptide synthesis (SPPS))

Credentials

  • Senior Scientist, Structural Biology & Bioinformatics, CSIR-IICB, Kolkata (2023-present)
  • Postdoctoral Fellow: Seoul National University, South Korea (2021-2023)
  • Visiting researcher: King’s College London, UK (Feb-March, 2019)
  • Postdoctoral Fellow: Tel Aviv University, Israel (2016-2021)
  • Ph.D. Indian Institute of Technology Guwahati (2016) 
  • M.Sc. Indian Institute of Technology (Indian School of Mines), Dhanbad (2010)
  • B.Sc. University of Burdwan (2008)

Honours & Awards

  • Guest Editor of special issues, “Therapeutic Development towards Protein Misfolding Diseases” and “Self-Assembling Peptides/Proteins at the Interface of Chemistry and Biology” in International Journal of Molecular Sciences, MDPI journal.
  • Topic Editor in International Journal of Molecular Sciences, MDPI journal.
  • Invited reviewer in journals: Chem. Sci., ACS Chem. Neurosci., Nanoscale, ACS Med. Chem. Lett., J. Agric. Food Chem., Front. Mol. Neurosci. Front. Mol. Biosci., Int. J. Mol. Sci., and Plant Foods Hum. Nutr.
  • Received APPD Postdoctoral Fellowship-2020/2021 from The Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease (APPD)
  • Awarded UK travel fellowship for one month (£2650) in 2018/2019 from British Council 
  • Awarded winning prize (₹10,000) on innovative research ideas leading to the entrepreneurial venture in biotechnology & allied areas, Assam Biotechnology Conclave, 20-21st November 2015.
  • Received Senior Research Fellowship (2013) and Junior Research Fellowship (2011) from UGC, India.
  • Qualified National Eligibility Test (NET-JRF) June-2011, Dec-2010 and June-2010 in Chemical Sciences.
  • Qualified Graduate Aptitude Test in Engineering (GATE) 2010 in Chemistry (All India rank 793).

Patents & Publications

Publications:

  1. Abu-Hussein M, Krishnakumar VG, Simhaev L, Paul A, Engel H, Gazit E, Segal D. The contribution of individual residues of an aggregative hexapeptide derived from the human γD-crystallin to its amyloidogenicity. Int. J. Biol. Macromol. 2022, 201, 182-192. DOI: 10.1016/j.ijbiomac.2021.12.192. (IF-8.028)
  2. Chakraborty P, Bera S, Mickel P, Paul A, Shimon LJW, Arnon ZA, Segal D, Král P, Gazit E. Inhibitor-Mediated Structural Transition in a Minimal Amyloid Model. Angew. Chem. Int. Ed. 2022, 61(3): e202113845. DOI: 10.1002/anie.202113845. (IF-16.823)
  3. Mohapatra S, Viswanathan GKK, Wettstein L, Arad E, Paul A, Kumar V, Jelinek R, Münch J, Segal D, Dual concentration-dependent effect of Ascorbic acid on PAP(248-286) amyloid formation and SEVI-mediated HIV infection. RSC Chem. Biol. 2021, 2, 1534-1545. DOI: 10.1039/D1CB00084E. (IF- 4.1)
  4. Paul A, Jacoby G, Beck R, Gazit E, Segal D. Glucosylceramide associated with Gaucher disease forms amyloid-like twisted ribbon fibrils that induce α-Synuclein aggregation. ACS Nano 2021, 15 (7), 11854−11868. DOI: 10.1021/acsnano.1c02957. (IF-18.027)
  5. Paul A, Krishnakumar VG, Huber A, Arad E, Engel H, Jelinek R, Gazit E, Segal D. Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone-Dopamine hybrid. FEBS J. 2021, 288 (14), 4267-4290. DOI: 10.1111/febs.15741. (IF-5.622)
  6. Paul A, Segal D, Zacco E. Glycans to improve efficacy and solubility of protein aggregation inhibitors. Neural Regen. Res. 2021, 16 (11), 2215-2216. DOI: 10.4103/1673-5374.310688. (IF-6.058)
  7. Kalita S, Kalita S, Paul A, Shah M, Kumar S, Mandal B. Site-Specific Single Point Mutation by Anthranilic Acid in hIAPP8-37 Enhances Anti-Amyloidogenic Activity. RSC Chem. Biol. 2021, 2, 266-273. DOI: 10.1039/D0CB00178C. (IF- 4.1)
  8. Paul A, Kumar S, Kalita S, Kalita S, Sarkar D, Bhunia A, Bandyopadhyay A, Mondal AC, Mandal B. An explicitly designed paratope of Amyloid-β prevents neuronal apoptosis in vitro and hippocampal damage in rat brain. Chem. Sci. 2021, 12, 2853-2862. DOI: 10.1039/D0SC04379F. (IF-9.969)
  9. Paul A, Huber A, Rand D, Gosselet F, Cooper I, Gazit E, Segal D. Naphthoquinone-Dopamine hybrids inhibit α-synuclein aggregation, disrupt preformed fibrils and attenuate aggregate-induced toxicity. Chem. Eur. J. 2020, 26(69), 16486-16496. DOI: 10.1002/chem.202003374. (IF-5.020)
  10. Paul A, Frenkel-Pinter M, Alvarez DE, Milordini G, Gazit E, Zacco E, Segal D. Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity. Commun. Biol. 2020, 3 (1), 484. DOI: 10.1038/s42003-020-01216-5. (IF-6.548)
  11. Abu-Hussein M, Krishnakumar VG, Haj E, Paul A, Gazit E, Segal D. An amyloidogenic hexapeptide from the cataract-associated γD-crystallin is a model for the full-length protein and is inhibited by naphthoquinone-tryptophan hybrids. Int. J. Biol. Macromol. 2020, 157, 424-433. DOI: 10.1016/j.ijbiomac.2020.04.079. (IF-8.025)
  12. Kalita S, Kalita S, Paul A, Sarkar A, Mandal B. Tail-to-Side Chain One Component Peptide Stapling Inhibits Alzheimer’s Amyloid-β Fibrillogenesis. Chem. Sci. 2020, 11, 4171-4179. DOI: 10.1039/C9SC06076F. (IF-9.969)
  13. Li G, Yang WY, Li WH, Luo YY, Lim YJ, Li Y, Paul A, Segal D, Hong L, Li YM. Rational design of a cocktail of inhibitors against Aβ aggregation. Chem. Eur. J. 2020, 26(16), 3499-3503. DOI: 10.1002/chem.201905621. (IF-5.020)
  14. Paul A, Li WH, Krishnakumar VG, Arad E, Mahapatra S, Li G, Jelinek R, Gazit E, Li YM, Segal D. Tryptophan-Glucosamine Conjugates Modulate Tau-Derived PHF6 aggregation at Low concentrations. Chem. Commun. 2019, 55 (97), 14621-14624. DOI: 10.1039/C9CC06868F. (IF-6.065)
  15. Krishnakumar VG, Paul A, Gazit E, Segal D. Naphthoquinone Tryptophan Hybrids: A Promising Small Molecule Scaffold for Mitigating Aggregation of Amyloidogenic Proteins and Peptides. Front. Cell Dev. Biol. 2019, 7, 242. DOI: 10.3389/fcell.2019.00242. (IF-6.081)
  16. Paul A, Krishnakumar VG, Mahapatra S, Balboni G, Pacifico S, Gazit E, Segal D. Antagonistic activity of Naphthoquinone based hybrid molecules towards Alzheimer’s and Type-2 diabetes diseases. ACS Chem. Neurosci. 2019, 10 (8), 3510. DOI: 10.1021/acschemneuro.9b00123. (IF-5.780)
  17. Paul A, Zhang BD, Mohapatra S, Li G, Li YM, Gazit E, Segal D. Novel Mannitol-Based Small Molecules for Inhibiting Aggregation of α-Synuclein Amyloids in Parkinson’s Disease. Front. Mol. Biosci. 2019, 6, 16. DOI: 10.3389/fmolb.2019.00016. (IF-6.113)
  18. Losev Y,# Paul A,# Frenkel-Pinter M, Abu-Hussein M, Khalaila I, Gazit E, and Segal D. Novel model of secreted human tau protein reveals the impact of the abnormal N-glycosylation of tau on its aggregation propensity. Sci. Rep. 2019, 9, 2254. (#equal contributors). DOI: 10.1038/s41598-019-39218-x. (IF-4.996)
  19. KrishnaKumar VG, Mahapatra S, Paul A, Gazit E, Segal D. Inhibitory effect of NQTrp hybrid towards PAP f39 semen amyloid aggregation. Molecules 2019, 23(12), 3279. DOI: 10.3390/molecules23123279. (IF-4.927)
  20. KrishnaKumar VG,# Paul A,# Gazit E, Segal D. Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids. Sci Rep. 2018, 8(1), 71. (#equal contributors) DOI: 10.1038/s41598-017-18443-2. (IF-4.996)
  21. Paul A, Kumar S, Kalita S, Ghosh AK, Mondal AC, Mandal B. A Peptide Based Pro-Drug Disrupts Alzheimer’s Amyloid into Non-Toxic Species and Reduces Aβ Induced Toxicity in vitro. Int. J. Pept. Res. Ther. 2018, 24(1) 201–211. DOI: 10.1007/s10989-017-9602-8. (IF-2.191)
  22. Giri RS, Manne SR, Dolai G, Paul A, Kalita T, Mandal B. FeCl3‑Mediated Side Chain Modification of Aspartic Acid- and Glutamic Acid-Containing Peptides on a Solid Support. ACS Omega 2(10), 6586−6597. DOI: 10.1021/acsomega.7b01143. (IF-4.132)
  23. Kumar S, Paul A, Kumar A, Hazra S, Ghosh AK, Mondal B, Mondal AC. A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells. Curr. Alzheimer Res. 2017, 14 (12), 1293-1304. DOI: 10.2174/1567205014666170713153414. (IF-3.040)
  24. Prasad S, Mandal I, Singh S, Paul A, Mandal B, Venkatramani R, Swaminathan R. Near UV-Visible Electronic Absorption Originating from Charged Amino Acids in a Monomeric Protein. Chem. Sci. 2017, 8, 5416-5433. DOI: 10.1039/C7SC00880E. (IF-9.969)
  25. Brahmachari S, Paul A, Segal D, Gazit E. Inhibition of amyloid oligomerization into different supramolecular architectures by small molecules: mechanistic insights and design rules. Future Med. Chem. 2017, 9(8), 797-810. DOI: 10.4155/fmc-2017-0026. (IF-4.767)
  26. Paul A, Kalita S, Kalita S, Sukumar P, Mondal B. Disaggregation of Amylin Aggregate by Novel Conformationally Restricted Aminobenzoic Acid containing α/β and α/γ Hybrid Peptidomimetics. Sci. Rep. 2017, 7, 40095. DOI: 10.1038/srep40095. (IF-4.996)
  27. Kumar S, Paul A, Kalita S, Ghosh AK, Mandal B, Mondal AC. Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro. Chem Biol Drug Des. 2017, 89 (6), 888–900. DOI: 10.1111/cbdd.12912. (IF-2.873)
  28. Sharma B, Kalita S, Paul A, Mandal B, Paul S. The role of caffeine as an inhibitor in the aggregation of amyloid forming peptides: a unified molecular dynamics simulation and experimental study. RSC Adv. 2016, 6, 78548–78558. DOI: 10.1039/C6RA17602J. (IF-4.036)
  29. Prasad S, Mandal I, Paul A, Mandal B, Venkatramani R, Swaminathan R. Investigation of Novel Spectroscopic Features in the Near Ultraviolet Region Arising from Non-Aromatic Amino Acids in Peptides and Proteins. Biophys. J. 2016, 110, 489a. DOI: 10.1016/j.bpj.2015.11.2614. (IF-3.699)
  30. Paul A, Sharma B, Mondal T, Thalluri K, Paul S, Mandal B. Amyloid-β Derived Switch-Peptides as a Tool for Investigation of Early Events of Aggregation: A Combined Experimental and Theoretical Approach. MedChemComm 2016, 7, 311-316. DOI: 10.1039/C5MD00466G. (IF-5.121)
  31. Manne SR, Thalluri K, Giri RS, Paul A, Mandal B. Racemization free longer N-terminal peptide hydroxamate synthesis on solid support using ethyl 2-(tert-butoxycarbonyloxyimino)-2-cyanoacetate. Tetrahedron Lett. 2015, 56, 6108–6111. DOI: 10.1016/j.tetlet.2015.09.084. (IF-2.032)
  32. Paul A, Nadimpally KC, Mondal T, Thalluri K, Mandal B. Inhibition of Alzheimer’s Amyloid-β Peptide Aggregation and its Disruption by a Conformationally Restricted α/β Hybrid Peptide. Chem. Commun. 2015, 51, 2245‒2248. DOI: 10.1039/C4CC09063B. (IF-6.065)
  33. Thalluri K, Paul A, Manne SR, Dev D, Mandal B. Microwave Assisted Chemoselective Organocatalytic Peptide Alcohol Synthesis from C-terminal Amide. RSC Adv. 2014, 4, 47841‒47847. DOI: 10.1039/C4RA09091H. (IF-4.036)
  34. Nadimpally KC, Paul A, Mandal B. Reversal of aggregation using β breaker dipeptide containing peptides: Application to Aβ1-40 self-assembly and its inhibition. ACS Chem. Neurosci. 2014, 5, 400–408. DOI: 10.1021/cn500064z. (IF-5.780)
  35. Saha A, Nadimpally KC, Paul A, Kalita S, Mandal B. Phenolic ester mediated oligopeptide synthesis promoted by HOBt. Protein Pept. Lett. 2014, 21, 188–193. DOI: 10.2174/09298665113206660097. (IF-1.927)
  36. Nadimpally KC, Paul A, Saha A, Mandal B. Modulation of Aggregation Propensity of Aβ38 by Site Specific Multiple Proline Substitution. Int. J. Pept. Res. Ther. 2013, 19, 365–371. DOI: 10.1007/s10989-013-9360-1. (IF-2.191)
  37. Thalluri K, Nadimpally KC, Chakravarty MP, Paul A, Mandal B. Ethyl 2-(tert-Butoxycarbonyloxyimino)-2-Cyanoacetate (Boc-Oxyma) as Coupling Reagent for Racemization free Esterification, Thioesterification, Amidation and Peptide Synthesis. Adv. Synth. Catal. 2013, 355, 448–462. DOI: 10.1002/adsc.201200645. (IF- 5.981)
  38. Thalluri K, Nadimpally KC, Paul A, Mandal B. Waste reduction in amide synthesis by a continuous method based on recycling of the reaction mixture. RSC Adv. 2012, 2, 6838–6845. DOI: 10.1039/C2RA20643A. (IF-4.036) 

 

Google Scholar: https://scholar.google.co.in/citations?user=pJAtHWoAAAAJ&hl=en

Patents:

  1. Mandal, B., and Paul, A. “Beta Sheet Breaker Peptides for Anti-Alzheimer's Drug Design” an Indian patent application, IPA No. E-2/1727/2015/KOL (complete application filed on the 17th September, 2015); provisional IPA No - 997/KOL/2014 (filed on the 26th September, 2014).
  2. Mandal, B., and Paul, A. “β-Sheet breaker peptides for drug design against Diabetes type-2” an Indian patent application, IPA No. 201631018104 (complete application filed on 26 May, 2016). Patent granted on 24 March 2021 (Patent no. 362950).

 

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