The Shemesh group is creating new technologies to understand and treat brain disease, a field we call “disease neuroengineering”. There are over 400 diseases of the nervous system, and we keep falling short of understanding their causes. What delays us, is the lack of adequate research technologies. At this point in scientific history, we simply do not have the tools to accurately and objectively understand the origins of brain disorders. In recent years, we have seen an explosion in tools that aim at understanding computation in the brain. These tools include optogenetic molecules, calcium or voltage sensors, single cell sequencing tools, novel microscopies, etc. However, as powerful as these tools are, in their current form they are not enough to unveil the seeding cellular and molecular events that culminate in brain pathogenesis.
Our group is therefore taking the technological approach to understanding diseases of the nervous system: we are creating tools that enable tracking the etiology of brain disease. Among these tools are sensors for the viability states of cells (is a cell healthy, necrotic or apoptotic?), actuators that switch brain cells and brain regions from healthy to a diseased state and back, novel animal models for basic research and drug screening, and devices for interfacing with the nervous system and repairing it. To build the tools, we combine experience in protein and genetic engineering, nanotechnology, cell biology, neuroscience, computational biology and electrical engineering. We encourage independent, radical, dogma-shattering thinking, and collaborations among peers and other groups. Group members can choose whether they want to focus on building technology, or on solving a scientific question using this technology. The technologies our group create can be applied to other research fields such as cancer, immunology and infectious diseases. No prior expertise in tool building or biology is needed, just passion and an open mind.
Representative Publications
Precision calcium imaging of dense neural populations via a cell body-targeted calcium indicator.
Shemesh OA.*, Linghu C*, Piatkevich KD*, Goodwin D, Freifeld L, Gritton HJ, Romano MF, BenSussen S, Tseng HA, Siciliano CA, Gupta I, Pak N, Young YG, Park W, Keating A, Tye K, Tolias A, Han X, Ahrens M, Boyden ES.
Neuron (Accepted) bioRxiv
Population imaging of neural activity in awake behaving mice in multiple brain regions.
Piatkevich KD, Bensussen S, Tseng H, Shroff SN, Lopez-Huerta VG, Park D, Jung EE, Shemesh OA, Straub C, Gritton HJ, Romano MF, Costa E, Sabatini BL, Fu Z, Boyden ES, Han X.
Nature (Accepted) BioRxiv
Membrane-targeted delivery of nitrogen vacancy nanodiamonds.
Shemesh OA.*, Gupta I*, Gaathon O, Wassie A, Foy C, Chang JB, Walcott A, Kodandaramaiah S, Wickersham I, Englund D, Boyden ES.
Under revision
A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters.
Piatkevich KD, Jung EE, Straub C, Linghu C, Park D, Suk HJ, Hochbaum DR, Goodwin D, Pnevmatikakis E, Pak N, Kawashima T, Yang CT, Rhoades JL, Shemesh OA, Asano S, Yoon YG, Freifeld L, Saulnier JL, Riegler C, Engert F, Hughes T, Drobizhev M, Szabo B, Ahrens MB, Flavell SW, Sabatini BL, Boyden ES.
Nature Chemical Biology (2018)
Temporally precise single-cell-resolution optogenetics.
Shemesh OA.*, Tanese D*, Zampini V*, Linghu C, Piatkevich KD, Ronzitti E, Papagiakoumou E, Emiliani V, Boyden ES.
Nature Neuroscience (2017)
Rescue of neurons from undergoing hallmark tau-induced Alzheimer's disease cell pathologies by the antimitotic drug paclitaxel.
Shemesh OA & Spira ME
Neurobiology of Disease (2011)
Hallmark cellular pathology of Alzheimer’s disease induced by mutant human-tau expression in cultured Aplysia neurons.
Shemesh OA & Spira ME
Acta Neuropathologica (2010)
Paclitaxel induces microtubule polar reorientation and impaired organelle transport in neurons – implications to taxane-induced neuropathy.
Shemesh OA & Spira ME
Acta Neuropathologica (2010)
Tau-induced microtubules reorientation and displacement leads to axonal traffic jams and neurodegeneration.
Shemesh OA., Erez H., Gizburg I., Spira ME.
Traffic (2008)
* denotes equal contribution