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Kunal Bhattacharya

Assistant professor

Visiting address : Scheelelaboratoriet, Nobelsväg 13 Solna, Sweden
Postal address : Institute of Environmental Medicine (IMM), C6, Molecular Toxicology, Box 210 171 77 Stockholm, Sweden
Delivery address : Scheelelaboratoriet, Nobelsväg 13 Solna, Sweden

About me

European Registered Toxicologist with 14+ years experience in the field of occupational and environmental exposure to particle and fiber toxicology. 

Education

2005 - 2008: Ph.D. (Dr. rer. Nat.) in Particle Toxicology from University of Duisburg-Essen, Essen, Germany. Grade: Magna cum laude

Thesis title: Comparative analysis of fine and nanoparticles for cellular uptake, oxidative stress and genomic damage in human lung cells.

1998 - 2000: M.Sc. in Life Sciences from University of Lucknow, Lucknow, India.

1995 - 1998: B.Sc. in Life Sciences from University of Lucknow, Lucknow, India.

Research description

Research Project 1: Cytotoxicity and immunotoxicity profiling of a panel of nineteen engineered nanomaterials from the FP7-NANOREG project enables ranking and grouping.

Engineered nanomaterials (ENMs) are being produced for an increasing number of applications and it is therefore important to perform safety assessment on ENMs. Here, we performed cytotoxicity and immunotoxicity screening of 19 ENMs in the frame of the EU-funded project, FP7-NANOREG using human macrophage-differentiated THP.1monocytes as a model. Based on IC-50 values we could rank the ENMs and show that the MWCNTs, ZnO, Ag and SiO2 nanomaterials were highly cytotoxic o the THP.1 cells. Inflammatory potential profiling of the ENMs was performed by measuring the cytokine, chemokine, and growth factor secretion from the THP.1 cells using a 27-mer multi-plex array (Bio-Plex Human 27-Plex Cytokine from Bio-Rad Laboratories) at sub-toxic dosage and hierarchical clustering analysis. We observed the iTiO2, SiO2, BaSO4, and CeO2 nanoparticles, as well as the nanocelluloses induced potent inflammatory responses in THP.1 cells at sub-cytotoxic doses.We could also segregate the ENMs into two distinct groups activating/ deactivating the PPAR/LXR nuclear receptor pathways relaetd to the release of inflammatory cyto-, chemokine and growth factors in the THP.1 cells. The present studies have shown that inflammatory responses of ENMs may be seen at non-cytotoxic doses, and that ENM can be grouped and ranked according to their cytotoxicity and inflammatory potential.

 

Research Project 2: Raman spectroscopy/microscopy for in situ monitoring of trafficking and degradation of polyethylene glycol modified single-walled carbon nanotubes.

Osteoarthritis (OA) is characterized by the breakdown of the extracellular (EC) articular cartilage driven by the transformation of chondrocytes from cartilage-producing (anabolic state) to cartilage-degrading (catabolic state) cells. Research in the field of disease modifying OA drugs (DMOAD) is hampered by low cartilage penetration and rapid clearance from synovial region. Nanomedicines such as polyethylene glycol modified single-walled carbon nanotube (PSNTs) that can be fabricated by loading therapeutic and/or imaging payloads and made to accumulate in diseased tissues/cells have shown promise as new DMOADs. Previous studies have demonstrated that PSNTs can deliver morpholino antisense oligomers in knee-joints of normal and OA mice. Furthermore, in a recent ex vivo study, PSNTs were shown to undergo enzymatic degradation by neutrophils. To explore the in vivo fate of PSNTs, we studied the residence, trafficking, and biodegradation of intra-articularly (IA) injected PSNTs in the knee-joint of healthy mice using Raman spectroscopy at different time-points post-exposure. To this end, a label-free detection method based on confocal mapping of the Raman intensity of the PSNTs asymmetric mode peak (D-band, ∼1350 cm−1) and that of tangential C–C stretching modes (G-band, ∼1598 cm−1), as well as the G-band intensity was employed to track the nanotubes in the different regions of the knee-joint of healthy mice and to assess their degradation in situ. We found that the IA-injected PSNTs persisted for more than 2 weeks in healthy mice knee-joints and penetrated deep into the both cartilage and meniscus EC matrices, while egressing from the joint cavity through the synovium. Raman D:G band ratio analysis showed that oxidative degradation of the PSNTs started within 24 h in the synovium and occurred in the superficial cartilage zone and meniscus between day 3 and day 21 after IA administration. To further study the biodegradation mechanism, we exposed murine chondrogenic ATDC-5 cell line activated with IL-1β to PSNTs and analyzed the oxidative damage by Raman spectroscopy. Using IL-1β stimulated cells, we found that chondrocytes induced oxidative damage to PSNTs and this was significantly reduced when the cells were co-incubated with pharmacological inhibitors of the NADPH oxidase or inducible nitric oxide synthase (iNOS). The study has demonstrated that PSNTs are cleared from the knee-joint through trafficking and degradation and the in vitro results suggest that PSNTs can be efficiently degraded by activated chondrocytes. Our study paves the way for the use of PSNTs as efficient systems in the treatment of OA. 

Teaching portfolio

Teaching experience

- Supervision of practical class for Masters course in Toxicology at Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (2013, 2015, 2016).

- Lecture in Masters course in Toxicology at Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (2013, 2015).

- Doctoral Research Project Co-supervisor = 2 (Completed; Dublin Institute of Technology, Dublin, Ireland, 2012 and Karolinska Institutet, Stockholm, Sweden, 2015).

- Masters Research Project Co-supervisor = 2 (Completed; Dublin Institute of Technology, Dublin, Ireland, 2012 and Karolinska Institutet, Stockholm, Sweden, 2014).

- Undergraduate Research Project Supervisor = 2 students (Dublin Institute of Technology, Dublin, Ireland, 2009).

 

Pedagogical courses done 

2013: ‘Basic course in doctoral supervision’, course conducted by Karolinska Institute, Stockholm, Sweden.

2014: ‘Advanced pedagogue course in doctoral supervision’, course conducted by Karolinska Institute, Stockholm, Sweden.

Academic honors, awards and prizes

Awards and research grants:

2015: Karolinska Institutet Foundation grant for research.

2014: Karolinska Institutet Foundation grant for research.

2013: Karolinska Institutet Foundation grant for research.

2013: Best Poster Award, 2nd QNano conference, Prague, Czech Republic.

2011: Travel Grant from Health Research Board (Ireland) and National Cancer Institute (NCI, United States) to attend 'Molecular mechanism of cancer' course held at NCI, United States.

2009: Research Grant from UREKA, Science Foundation of Ireland, Ireland.

2009: Young Scientist Award from University Duisburg-Essen, Essen, Germany.

2008: Travel Grant from Deutsche Forschungsgemeinschaft for attending 47th Annual Society of Toxicology meeting, Seattle, United States.

2007: Best Poster Award, EnTox, Dortmund, Germany.

 

Invited lectures:

2016: Session chair for ‘Hazard Assessment – In vitro approach’ in 2nd Nanosafety forum for young scientists, Visby, Gotland, Sweden 15th -16th of September, 2016.

2015: Materials day, Rostock University, Rostock, Germany.

2013: Nanometer Structure Consortium Lund University, Lund, Sweden.

2010: Department of Inorganic Chemistry, University of Duisburg-Essen, Essen, Germany.

2009: Department of Research and development, Integral University, Lucknow, India.

2005: Institute of Hygiene and Occupational Medicine, University Hospital, Essen, Germany.

Documents

Publications

Biological interactions of carbon-based nanomaterials: From coronation to degradation
Bhattacharya K, Mukherjee Sp, Gallud A, Burkert Sc, Bistarelli S, Bellucci S, et al
Nanomedicine : nanotechnology, biology, and medicine 2016;12(2):333-51

Nanodrugs to target articular cartilage: An emerging platform for osteoarthritis therapy
Bottini M, Bhattacharya K, Fadeel B, Magrini A, Bottini N, Rosato N
Nanomedicine : nanotechnology, biology, and medicine 2016;12(2):255-68

Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4
El-sayed R, Bhattacharya K, Gu Z, Yang Z, Weber Jk, Li H, et al
Scientific reports 2016;6():21316-

Dual effects of beta-cyclodextrin-stabilised silver nanoparticles: enhanced biofilm inhibition and reduced cytotoxicity
Jaiswal S, Bhattacharya K, Mchale P, Duffy B
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE 2015;26(1):5367-

Keeping it real: The importance of material characterization in nanotoxicology
Fadeel B, Fornara A, Toprak Ms, Bhattacharya K
Biochemical and biophysical research communications 2015;468(3):498-503

Lactoperoxidase-mediated degradation of single-walled carbon nanotubes in the presence of pulmonary surfactant
Bhattacharya K, El-sayed R, Andon Ft, Mukherjee Sp, Gregory J, Li H, et al
CARBON 2015;:506-517

Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
Bhattacharya K, Sacchetti C, El-sayed R, Fornara A, Kotchey Gp, Gaugler Ja, et al
Nanoscale 2014;6(24):14686-90

Extracellular entrapment and degradation of single-walled carbon nanotubes
Farrera C, Bhattacharya K, Lazzaretto B, Andón Ft, Hultenby K, Kotchey Gp, et al
Nanoscale 2014;6(12):6974-83

Shifting identities of metal oxide nanoparticles: Focus on inflammation
Bhattacharya K, Farcal L, Fadeel B
MRS BULLETIN 2014;39(11):970-975

Geoengineering: Perilous Particles
Fadeel B, Karlsson Hl, Bhattacharya K
SCIENCE 2013;340(6132):548-9

Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation
Bhattacharya K, Andón Ft, El-sayed R, Fadeel B
Advanced drug delivery reviews 2013;65(15):2087-97

Non-cytotoxic antibacterial silver-coumarin complex doped sol-gel coatings
Jaiswal S, Bhattacharya K, Sullivan M, Walsh M, Creaven Bs, Laffir F, et al
COLLOIDS AND SURFACES B-BIOINTERFACES 2013;:412-9

Comparison of Micro- and Nanoscale Fe+3-Containing (Hematite) Particles for Their Toxicological Properties in Human Lung Cells In Vitro
Bhattacharya K, Hoffmann E, Schins Rfp, Boertz J, Prantl Em, Alink Gm, et al
TOXICOLOGICAL SCIENCES 2012;126(1):173-82

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles
Bhattacharya K, Naha Pc, Naydenova I, Mintova S, Byrne Hj
TOXICOLOGY LETTERS 2012;215(3):151-60

Imaging live cells grown on a three dimensional collagen matrix using Raman microspectroscopy
Bonnier F, Knief P, Lim B, Meade Ad, Dorney J, Bhattacharya K, et al
ANALYST 2010;135(12):3169-77

Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480)
Naha Pc, Bhattacharya K, Tenuta T, Dawson Ka, Lynch I, Gracia A, et al
TOXICOLOGY LETTERS 2010;198(2):134-43

Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips
Gramowski A, Flossdorf J, Bhattacharya K, Jonas L, Lantow M, Rahman Q, et al
Environmental health perspectives 2010;118(10):1363-9

Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells
Bhattacharya K, Davoren M, Boertz J, Schins Rp, Hoffmann E, Dopp E
Particle and fibre toxicology 2009;6():17-

Vanadium pentoxide-coated ultrafine titanium dioxide particles induce cellular damage and micronucleus formation in V79 cells
Bhattacharya K, Cramer H, Albrecht C, Schins R, Rahman Q, Zimmermann U, et al
Journal of toxicology and environmental health. Part A 2008;71(13-14):976-80

Cellular uptake and toxicity of inhalable arsenopyrite particles and of its natural analogue hematite.
Bhattacharya K, Hoffmann E, Hartmann Lm, Albrecht C, Rettenmeier Aw, Dopp E
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2007;:78-79

Biomarkers in risk assessment of asbestos exposure
Bhattacharya K, Dopp E, Kakkar P, Jaffery Fn, Schiffmann D, Jaurand Mc, et al
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 2005;579(1-2):6-21

ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro
Dopp E, Yadav S, Ansari Fa, Bhattacharya K, Von Recklinghausen U, Rauen U, et al
Particle and fibre toxicology 2005;2():9-

Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood lymphocytes by garlic extract
Bhattacharya K, Yadava S, Papp T, Schiffmann D, Rahman Q
TOXICOLOGY LETTERS 2004;153(3):327-32

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Presentations

- Bhattacharya K, Mukherjee S, El-Sayed R, et al.  Lactoperoxidase mediated biodegradation of single-walled carbon nanotubes: implications for respiratory exposure to carbon nanotubes. 11th International Particle Toxicology Conference, Singapore, 2016 (Oral Presentation).
- Bhattacharya K, Kilic G, Fadeel B, Cyto- and immunotoxicity analysis of a panel of nineteen representative nanomaterials in a human monocyte-macrophage cell model: results from EU FP7-NANOREG. 2nd Nanosafety forum for young scientists, Visby, Gotland, Sweden, 2016 (Oral Presentation).
- Mukherjee SP, Lazzaretto B, Bhattacharya K, et al. Graphene Oxide Interactions with Innate Immune Cells: Extracellular Trap Formation and Inflammasome Activation. 8th International Nanotoxicology Congress, Boston, United States, 2016 (Poster Presentation).
- Bhattacharya K, Sacchetti C, El-Sayed R, et al., Enzymatic -stripping’ and degradation of PEGylated single-walled carbon nanotubes by neutrophils elastase and myeloperoxidase, SENN conference, Helsinki, Finland, 2015 (Oral Presentation).
- Bhattacharya K, Farrera C, Andón FT, et al. Extracellular entrapment and degradation of single-walled carbon nanotubes, 7th International nanotoxicology conference, Antalya, Turkey, 2014 (Poster Presentation).
Bhattacharya K, Andón FT, Fornara A,  et al. Lactoperoxidase mediated biodegradation of carboxylated single-walled carbon nanotubes, 2nd QNano conference, Prague, Czech Republic, 2013 (Oral Presentation).
Carey K, Bhattacharya K, Byrne HJ, et al. Preliminary Eco-nanotoxicity results of C60 and Carbon Black assessed by established tests over a range of trophic levels in the Aquatic environment, NanoImpactNet Conference, Lausanne, Switzerland, 2011 (Poster Presentation).
Bhattacharya K, Naydenova I, Mintova S, Byrne HJ. Biocompatibility of Zeolite-MFI nanoparticles in human lung cells, NanoImpactNet Conference, Lausanne, Switzerland 2011 (Poster Presentation).
Carey K, Bhattacharya K, Byrne HJ, et al. Eco-Nanotoxicity results of C60 and Carbon Black assessed by established Ecotoxicity tests over a range of Trophic levels in the Aquatic environment, Proceedings of the microscopy society of Ireland Annual Symposium, Dublin, 2011 (Poster Presentation).