Alireza Mashaghi | |
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| Alma mater | Harvard University,Delft University of Technology,ETH Zurich,University of Tehran |
| Known for | Single-molecule analysis of protein folding Circuit topology Statistical physics of medical diagnostics Organ chips for viral diseases Immunomechanics |
| Awards | Discoverer of the Year 2018, Muscular Dystrophy Association Award (2019), KIA Laureate (2025) |
| Scientific career | |
| Fields | Physics,Medicine |
| Institutions | Leiden University,Harvard University |
Alireza Mashaghi is aphysician-scientist and biophysicist atLeiden University.[1] He is known for his contributions tosingle-molecule analysis ofchaperone assistedprotein folding,molecular topology and medical systems biophysics and bioengineering. He is a leading advocate forinterdisciplinary research and education inmedicine andpharmaceutical sciences.
Mashaghi made the first observation of directchaperone involvement during folding of a protein, using asingle moleculeforce 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 chaperoneDnaK 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 useoptical tweezers to study folding of a single protein molecule in acytosol, 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 ascircuit topology, which enabled studying folded molecular chains, beyond whatknot theory can offer.[5] The approach allows for topological barcoding of proteins and cellular genomes for medical applications.[6][7] In recent years, the team got interested in disease-relatedbiomolecular condensates and thus extended the force spectroscopy and circuit topology approaches to study these complex systems. In particular, the group introduced multi-chain circuit topology framework applicable to biomolecular condensate[8] and developed the first of its kind scanning probe microscopic assay for condensate analysis.[9]
Mashaghi also contributed to others areas in biophysics and bioengineering includingmembrane biophysics, membrane basedlab-on-a-chip biosensing,[10][11] andorgan-on-a-chip technology. In particular, the Mashaghi team was one of the first to introduce Organ Chip technology to the field ofvirology.[12] His team engineered the first chip-based disease model forEbolahemorrhagic shock syndrome, and later extended the applicability of the platform to various viral haemorrhagic syndromes.[13] Ebola and similar viruses pathologically alter the mechanics of human cells, which is recapitulated in organ chip models. Moreover, the Mashaghi team developedoptical tweezers and acousticforce spectroscopy based assays to probe such mechanical alterations at the single cell level.[14]
Mashaghi is also active in interdisciplinary research inophthalmology,immunopathology andmedicine. His main contributions were in the areas of ocularinflammation andimmunomodulation. In 2017, he and his co-workers at Harvard developed an immunotherapy strategy to improve survival of high-riskcornea grafts.[15] Together with his co-workers, he contributed to the use ofstem cell technology andomics 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.[16] Additionally, his lab was the first to measure human macrophagemechanics andmetabolome using single-cell approaches. Finally, in their research, Mashaghi and his co-workers are linkingstatistical physics andmedical diagnostics; this unprecedented link between physics and medicine may allow for early and efficient diagnosis of certain diseases.[17]
During his academic career, Mashaghi has been affiliated with various institutions includingHarvard University,Leiden University,Massachusetts Institute of Technology,Delft University of Technology,ETH Zurich,Max Planck Institutes, andAMOLF. Mashaghi has published more than 100 papers in peer-reviewed scientific journals including several papers inNature and Nature specialty journals. He worked and co-authored withHans Clevers,Cees Dekker,Anthony A. Hyman,Colin Adams,Erica Flapan,Donald E. Ingber,Huib Bakker,Reza Dana, andPetra Schwille.[18][19][20] He serves on editorial board of several journals includingNano Research.
In 2018, Mashaghi has been named as "Discoverer of the Year" by Leiden University.[21] He is the recipient of several awards including an honorarium fromAmerican Chemical Society.