# Alireza Mashaghi

Alireza Mashaghi is a physician-scientist and biophysicist at Leiden University. 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. 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". 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. 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. The approach allows for topological barcoding of proteins and cellular genomes for medical applications. In recent years, the team got interested in disease-related biomolecular 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 and developed the first of its kind scanning probe microscopic assay for condensate analysis.
Mashaghi also contributed to others areas in biophysics and bioengineering including membrane biophysics, membrane based lab-on-a-chip biosensing, 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. 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. 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.
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. 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. 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.
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. 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. He is the recipient of several awards including an honorarium from American Chemical Society.