Atin Kumar Mandal

Atin Kumar Mandal
Professor

Previous appointments:

2020-           Professor, Division of Molecular Medicine, Bose Institute, Kolkata

2015- 2020   Associate Professor, Division of Molecular Medicine, Bose Institute, Kolkata

2010-2015    Assistant Professor, Division of Molecular Medicine, Bose Institute, Kolkata

2008-2010    Research Associate, Department of Biology, The City College of New York, New York

2005-2007    Post Doctoral Fellow, Department of Pharmacology and System Therapeutics, Mount Sinai School of Medicine, New York                  

2003-2005    Research Associate, Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Massachusetts

2000-2003    Post Doctoral Fellow, Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Massachusetts

Research interests:

  • Understanding the mechanism of protein kinase quality control in development of pathological conditions such as cancer, cardiac hypertrophy
  • Crosstalk between molecular chaperones and ubiquitin ligases in quality control of misfolded aggregated prone proteins
  • Role of Praja1 ubiquitin ligase in maintaining cellular proteostasis

Contact:

Address: Biological Sciences
Unified Academic Campus
Bose Institute
EN-80, Sector V
Bidhan Nagar
Kolkata - 700 091, India
E-Mail: mandalak[at]jcbose.ac.in
Phone: +91-33-25693

Research:

Cellular protein quality control (PQC) maintains protein homeostasis at physiological or stress condition. Efficient clearance of misfolded proteins by refolding, degradation or sequestration is critical for cell survival. Molecular chaperones are integral part of PQC. Chaperones help in folding of several proteins linked with cell signaling and gene expression. Thus, chaperones become a potential target for various diseases including cancer, diabetes and even late-onset neurological diseases when efficiency of quality control decreases. However, quality control of such important chaperone clients such as protein kinases or misfolded proteins those are toxic for the cell is still elusive. Using both yeast and mammalian system I am trying to understand the mechanism of cellular protein quality control.



 Misfolded kinase accumulates into distinct cellular quality control inclusions upon stress



Hsp90 mediated regulation of CRAF kinase


Publications:

 ·       Ilyas H, van der Plas MJA, Agnoletti M, Kumar S, Mandal AK, Atreya HS, Bhunia A, Malmsten M. Effect of PEGylation on Host Defense Peptide Complexation with Bacterial Lipopolysaccharide. Bioconjug Chem. 2021 Aug 18;32(8):1729-1741. doi: 10.1021/acs.bioconjchem.1c00259.

·     Ghosh B, Karmakar S, Prasad M, Mandal AK. Praja1 ubiquitin ligase facilitates degradation of polyglutamine proteins and suppresses polyglutamine-mediated toxicity. Mol Biol Cell. 2021 Aug 15;32(17):1579-1593. doi: 10.1091/mbc.E20-11-0747.

·       Chakraborty I, Kar RK, Sarkar D, Kumar S, Maiti NC, Mandal AK, Bhunia A. Solvent Relaxation NMR: A Tool for Real-Time Monitoring Water Dynamics in Protein Aggregation Landscape. ACS Chem Neurosci. 2021 Aug 4;12(15):2903-2916. doi: 10.1021/acschemneuro.1c00262.

·     Bera S, Gayen N, Mohid SA, Bhattacharyya D, Krishnamoorthy J, Sarkar D, Choi J, Sahoo N, Mandal AK, Lee D, Bhunia A. Comparison of Synthetic Neuronal Model Membrane Mimics in Amyloid Aggregation at Atomic Resolution. ACS Chem Neurosci. 2020 Jul 1;11(13):1965-1977. doi: 10.1021/acschemneuro.0c00166.

·   Pariary R, Ghosh B, Bednarikova Z, Varnava KG, Ratha BN, Raha S, Bhattacharyya D, Gazova Z, Sarojini V, Mandal AK, Bhunia A. Targeted inhibition of amyloidogenesis using a non-toxic, serum stable strategically designed cyclic peptide with therapeutic implications. Biochim Biophys Acta Proteins Proteom. 2020 May; 1868(5):140378. doi: 10.1016/j.bbapap.2020.140378.

·   Sarkar D, Chakraborty I, Condorelli M, Ghosh B, Mass T, Weingarth M, Mandal AK, La Rosa C, Subramanian V, Bhunia A. Self-Assembly and Neurotoxicity of β-Amyloid (21-40) Peptide Fragment: The Regulatory Role of GxxxG Motifs. Chem Med Chem. 2020 Feb 5;15(3):293-301. doi: 10.1002/cmdc.201900620

·    Bhattacharyya D, Mohite GM, Krishnamoorthy J, Gayen N, Mehra S, Navalkar A, Kotler SA, Ratha BN, Ghosh A, Kumar R, Garai K, Mandal AK, Maji SK, Bhunia A. Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function. ACS Chem Neurosci. 2019 Mar 20. doi: 10.1021/acschemneuro.8b00733

·     Mitra S, Ghosh B, Gayen N, Roy J & Mandal AK. Bipartite role of Hsp90 keeps CRAF poised for activation. Journal of Biological Chemistry, 291, 23545-23556 (2016)

·   Ratha BN, Ghosh A, Brender JR, Gayen N, Ilyas H, Neeraja C, Das KP, Mandal AK & Bhunia A. Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide: Mechanistic Details Studied by Spectroscopy in Combination with Microscopy. Journal of Biological Chemistry, 291, 24579-24593 (2016)

·     Roy J, Mitra S, Sengupta K & Mandal AK. Hsp70 clears misfolded kinases that partitioned into distinct quality control compartments. Molecular Biology of Cell, 26, 1583-1600 (2015)

·    Ghosh A, Ratha BN, Gayen N, Mroue KH, Kar RK, Mandal AK*, Bhunia A.* Biophysical Characterization of Essential Phosphorylation at the Flexible C-Terminal Region of C-Raf with 14-3-3ζ Protein. PLoS One Aug 21;10(8) (2015) * Co-corresponding author

·      Roy J & Mandal AK. Cellular strategies to combat protein misfolding: Intricate role of Hsp70 in stress management. Current Chemical Biology, 8, 149-164 (2014)

·     Nillegoda NB, Theodoraki MA, Mandal AK, Mayo KJ, Ren HY, Sultana R, Wu K, Johnson J, Cyr DM, Caplan AJ.  Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins. Molecular Biology of Cell, 21, 2102-2116 (2010).

·   Mandal AK*, Gibney PA*, Nillegoda NB, Theodoraki MA, Morano KA & Caplan AJ. Hsp110 chaperones control client fate determination in the Hsp70-Hsp90 chaperone system. Molecular Biology of Cell 21, 1439-1448, 2010 *joint first authors

·    Mandal AK, Nillegoda N, Chen J & Caplan AJ. Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation. Molecular and Cellular Biology, 28 (13), 4434-4444 (2008)

·    Mandal AK, Lee P, Chen J, Nillegoda N, Heller H, DiStasio S, Oen H, Victor J, Nair NM, Brodsky JL & Caplan AJ. Cdc37 has distinct roles in protein kinase quality control that protects nascent chains from degradation and promotes post-translational maturation. Journal of Cell Biology, 176, 319-328 (2007)

·     Caplan AJ, Mandal AK & Theodoraki MA.  Molecular chaperones and protein kinase quality control. Trends in Cell Biology, 17(2), 87-92, (2007)

·     Robzyk K, Oen H, Buchanan G, Butler LM, Tilley W, Mandal AK, Rosen N, & Caplan AJ. Uncoupling of Hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Mol. Cell. Endocrinol., 268 (1-2):67-74, (2007)

·    Ying Y, Mandal AK, Bredeston LM, Gonzalez-Flecha FL & Argüello JM. Activation of Archaeoglobus fulgidus Cu+-ATPase CopA by cysteine. Biochim. Biophys. Acta. 1768, 495-501 (2007)

·  Sazinsky MH, Mandal AK, Argüello JM, & Rosenzweig AC. Structure of the ATP binding domain from the Archaeoglobus fulgidus Cu+-ATPase. Journal of Biological Chemmistry, 281, 11161-11166 (2006)

·    Mandal AK, Yang Y, Kertesz TM & Argüello JM. Identification of the transmembrane metal binding site in Cu+ transporting P1B-type ATPases. Journal of Biological Chemistry. 279, 54802-54807 (2004)

·    Mana-Capelli S, Mandal AK, & Argüello JM. Archaeoglobus fulgidus CopB is a thermophilic Cu2+-ATPase. Functional role of its His-rich N-terminal metal binding domain. Journal of Biological Chemistry 278, 40534-40541 (2003)

·     Mandal AK & Argüello JM. Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu+-ATPase CopA. Biochemistry, 42, 11040-11047 (2003)

·  Mandal AK, Cheung W & Argüello, JM. Characterization of a thermophilic P-type Ag+/Cu+ -ATPase from the extremophile Archaeoglobus fulgidus. Journal of Biological Chemistry, 277, 7201-7208, (2002)

·    Mikhaylova L, Mandal AK & Argüello JM. The catalytic phosphorylation of the Na,K-ATPase drives the outward movement of the cation-binding H5-H6 hairpin. Biochemistry, 41(25), 8195-8202, (2002)

·   Mandal AK, Roy K, Sil PC, Yadav SP & Sen PC. Purification, characterization and partial amino acid sequencing of a 70 kD inhibitor protein of Na+, K+-ATPase from goat testis cytosol. Mol. Cell. Biochem. 223, 7-14 (2001)

·    Roy K, Mandal AK & Sen PC.  A 75 kDa Na+,K+-ATPase competitive inhibitor protein isolated from rat brain cytosol binds to a site different from the ouabain-binding site. Eur. J. Biochem. 261, 84-88, 1999

·    Roy K, Mandal AK, Sikdar R, Majumder S, Ono Y & Sen PC.  Unsaturated fatty acid activated protein kinase (PKx) from goat testis cytosol. Biochim. Biophys. Acta. 1434, 161-169 (1999)

·       Sikdar R, Roy K, Mandal AK & Sen PC. Phosphorylation and dephosphorylation of Mg2+-independent Ca2+-ATPase from goat spermatozoa. J. Bioscience. 24, 317-321 (1999)


Book Chapters

·       Mandal AK, Nair DM & Caplan AJ. Role of Cdc37 in protein kinase folding.  In:“Protein Reviews” Vol. 7: Cell Stress Proteins (Edited by Stuart K. Calderwood) Springer. 326-337, 2007

·     Mandal AK, Mikhaylova L & Argüello JM. S5-H5 helix in the Na,K-ATPase: A structural link between phosphorylation and cation-binding sites. In: "The Na,K-ATPase and Related Cation Pumps" (Jorgensen, P.L., Maunsbach, A.B., and S.J.D., Karlish, Eds.) Annals. New York Acad. Sc. 224-225 (2003)

·    Argüello JM, Mandal AK & Mana-Capelli S. Heavy metal transport CPx-ATPases from the thermophile Archaeoglobus fulgidus. In: "The Na,K-ATPase and Related Cation Pumps" (Jorgensen, P.L., Maunsbach, A.B., and S.J.D., Karlish, Eds.) Annals. New York Acad. Sc. 212-218 (2003)

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Recognition:

    Teaching:

    Integrated Ph.D. course

    Enzyme kinetics,

    Cell stress response and Protein folding (MCB core)

    PhD coursework

    B.1. Enzymology

    Students:

    Image Name Designation Department Campus Contact number Email
    profile image Alapan Maity Junior Research Fellow Division of Molecular Medicine Unified maityalapan98@gmail.com
    profile image Gourav Shome Junior Research Fellow Division of Molecular Medicine Centenary gshome007@gmail.com
    profile image Madhuparna Chakraborty Junior Research Fellow Division of Molecular Medicine Centenary mauchak26@gmail.com
    profile image Somesh Roy Senior Research Fellow Division of Molecular Medicine Centenary someshroy.SR@gmail.com

    Former:


    Sahana Mitra, PhD, sahana.mitra84@gmail.com; Currently Post Doctoral Fellow at New York School of Medicine, New York, USA

    Joydeep Roy, PhD. jroy4u@gmail.com; Currently Wenner-Gren Foundations Post Doctoral Fellow at Stockholm University, Stockholm

    Debanjana Mitra, Project Assistant, shis.mitra@gmail.com; Currently at Biocon Biopharmaceutical Company, Bangalore




    Group News:

    • Congratulation Baijayanti for awarding PhD degree
    • Congratulation Baijayanti for winning FEBS LETTER poster prize at EMBO workshop
    • Baijayanti Ghosh received EMBO travel award to attend EMBO Workshop on ‘Protein quality control: From mechanisms to disease’; 28 April -03 May 2019, Costa de la Calma (Mallorca), Spain
    • Sept 08, 2018- Nilanjan Gayen gave a talk in one day symposium at Amity University organised by  SBC(I),  Kolkata Chapter