Alireza Mashaghi
Alma materHarvard University, Delft University of Technology, ETH Zurich, University of Tehran
Known forSingle-molecule analysis of protein folding
Circuit topology
Statistical physics of medical diagnostics
Organ chips for viral diseases
AwardsDiscoverer of the Year 2018, Muscular Dystrophy Association Award 2019
Scientific career
FieldsPhysics, Medicine
InstitutionsLeiden University, Harvard University

Alireza Mashaghi is a physician-scientist and biophysicist at Leiden University.[1] He is known for his contributions to single-molecule analysis of chaperone assisted protein folding, molecular topology and medical systems biophysics and bioengineering. He is a leading advocate for interdisciplinary research and education in medicine and pharmaceutical sciences.

Mashaghi made the first observation of direct chaperone involvement during folding of a protein, using a single molecule force spectroscopy method. This work which has been published in Nature solved a long-standing puzzle in biology.[2] In 2017, he reported a new model for chaperone DnaK function and made a discovery that, according to Ans Hekkenberg, "overturns the decades-old textbook model of action for a protein that is central for many processes in living cells".[3] He and his co-workers found that chaperone DnaK can recognise natively folded protein parts and thereby promotes protein folding directly. Furthermore, the lab was the first to use optical tweezers to study folding of a single protein molecule in a cytosol, revealing the collective contribution of chaperones to folding.[4] Inspired by single-molecule analysis of biopolymers, Mashaghi and his team developed a topology framework, termed as circuit topology, which enabled studying folded molecular chains, beyond what knot theory can offer.[5] The approach allows for topological barcoding of proteins and cellular genomes for medical applications.[6] [7]

Mashaghi also contributed to others areas in biophysics and bioengineering including membrane biophysics, membrane based lab-on-a-chip biosensing,[8][9] and organ-on-a-chip technology. In particular, the Mashaghi team was one of the first to introduce Organ Chip technology to the field of virology.[10] His team engineered the first chip-based disease model for Ebola hemorrhagic shock syndrome, and later extended the applicability of the platform to various viral haemorrhagic syndromes.[11] Ebola and similar viruses pathologically alter the mechanics of human cells, which is recapitulated in organ chip models. Moreover, the Mashaghi team developed optical tweezers and acoustic force spectroscopy based assays to probe such mechanical alterations at the single cell level.[12]

Mashaghi is also active in interdisciplinary research in ophthalmology, immunopathology and medicine. His main contributions were in the areas of ocular inflammation and immunomodulation. In 2017, he and his co-workers at Harvard developed an immunotherapy strategy to improve survival of high-risk cornea grafts.[13] Together with his co-workers, he contributed to the use of stem cell technology and omics technology in ophthalmology and medicine. Mashaghi and his co-workers were among the first to use stem cells to reprogram innate immune cells, including neutrophil and macrophages.[14] Additionally, his lab was the first to measure human macrophage mechanics and metabolome using single-cell approaches. Finally, in their research, Mashaghi and his co-workers are linking statistical physics and medical diagnostics; this unprecedented link between physics and medicine may allow for early and efficient diagnosis of certain diseases.[15]

During his academic career, Mashaghi has been affiliated with various institutions including Harvard University, Leiden University, Massachusetts Institute of Technology, Delft University of Technology, ETH Zurich, Max Planck Institutes, and AMOLF. Mashaghi has published more than 100 papers in peer-reviewed scientific journals including several papers in Nature and Nature specialty journals. He worked and co-authored with Hans Clevers, Cees Dekker, Anthony A. Hyman, Colin Adams, Erica Flapan, Donald E. Ingber, Huib Bakker, Reza Dana, and Petra Schwille.[16][17][18] He serves on editorial board of several journals including Nano Research.

In 2018, Mashaghi has been named as "Discoverer of the Year" by Leiden University.[19] He is the recipient of several awards including an honorarium from American Chemical Society.

References

  1. ^ The Mashaghi group, LACDR, Leiden University
  2. ^ "A Rubik's cube at the nanoscale: proteins puzzle with amino acid chains". Archived from the original on 2019-01-06. Retrieved 2017-12-13.
  3. ^ Universal clamping protein stabilizes folded proteins: New insight into how the chaperone protein Hsp70 works
  4. ^ University, Leiden. "Biological origami at molecular level: Cytosolic interactome protects against protein unfolding". phys.org.
  5. ^ Mashaghi, Alireza; Van Wijk, Roeland J.; Tans, Sander J. (2014). "Circuit Topology of Proteins and Nucleic Acids". Structure. 22 (9): 1227–1237. doi:10.1016/j.str.2014.06.015. PMID 25126961.
  6. ^ Yasuyuki Tezuka, Tetsuo Deguchi, Topological Polymer Chemistry: Concepts and Practices (2022) ISBN 978-981-16-6807-4
  7. ^ Leiden scientists develop topological barcodes for folded molecules
  8. ^ "Conformation Activity Relationships - Why Do Molecules Change Shape?". 14 February 2010.
  9. ^ Mashaghi, S.; Jadidi, T.; Koenderink, G.; Mashaghi, A. (2013). "Lipid Nanotechnology". International Journal of Molecular Sciences. 14 (2): 4242–4282. doi:10.3390/ijms14024242. PMC 3588097. PMID 23429269.}
  10. ^ Tang, Huaqi; Abouleila, Yasmine; Si, Longlong; Ortega-Prieto, Ana Maria; Mummery, Christine L.; Ingber, Donald E.; Mashaghi, Alireza (2020). "Human Organs-on-Chips for Virology". Trends in Microbiology. 28 (11): 934–946. doi:10.1016/j.tim.2020.06.005. PMC 7357975. PMID 32674988.
  11. ^ Junaid, Abidemi; Tang, Huaqi; Van Reeuwijk, Anne; Abouleila, Yasmine; Wuelfroth, Petra; Van Duinen, Vincent; Stam, Wendy; Van Zonneveld, Anton Jan; Hankemeier, Thomas; Mashaghi, Alireza (2020). "Ebola Hemorrhagic Shock Syndrome-on-a-Chip". iScience. 23 (1): 100765. Bibcode:2020iSci...23j0765J. doi:10.1016/j.isci.2019.100765. PMC 6941864. PMID 31887664.
  12. ^ Evers, Tom M.J.; Sheikhhassani, Vahid; Haks, Mariëlle C.; Storm, Cornelis; Ottenhoff, Tom H.M.; Mashaghi, Alireza (2022). "Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics". iScience. 25 (1): 103555. Bibcode:2022iSci...25j3555E. doi:10.1016/j.isci.2021.103555. PMC 8693412. PMID 34988399.
  13. ^ "Preventing graft rejection in high-risk corneal transplant patients".
  14. ^ Mashaghi-Tabari, Alireza; Dana, Reza; Chauhan, Sunil (June 2015). "Mesenchymal stem cells suppress innate immune response to corneal injury". Investigative Ophthalmology & Visual Science. 56 (7): 4356.
  15. ^ Diagnosing patients with the help of statistical physics (2018) [1]
  16. ^ Mashaghi A et al. Biophysical Journal 95 (11), p5476–5486 (2008)
  17. ^ Inomata, Takenori; Mashaghi, Alireza; Di Zazzo, Antonio; Lee, Sang-Mok; Chiang, Homer; Dana, Reza (2017). "Kinetics of Angiogenic Responses in Corneal Transplantation". Cornea. 36 (4): 491–496. doi:10.1097/ICO.0000000000001127. PMC 5334361. PMID 28060028.
  18. ^ Vlijm, R.; Mashaghi, A.; Bernard, S.; Modesti, M.; Dekker, C. (2015). "Experimental phase diagram of negatively supercoiled DNA measured by magnetic tweezers and fluorescence". Nanoscale. 7 (7): 3205–3216. Bibcode:2015Nanos...7.3205V. doi:10.1039/c4nr04332d. PMID 25615283.
  19. ^ Our Talents & Discoveries 2017 - Universiteit Leiden
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