Sarah Shahmoradian, Ph.D. - Faculty Profile

Biography

Sarah Shahmoradian, born and raised in Richmond, Virginia, received her Ph.D. in Molecular Physiology and Biophysics from Baylor College of Medicine in 2013, under mentorship of Wah Chiu, now at Stanford. She used cryo-electron microscopy (cryo-EM) and tomography (cryo-ET) to reveal structural mechanisms behind the aggregation and modulation of key proteins in neurodegeneration. Her research explained how the chaperonin TRiC/CCT inhibits Huntingtin protein aggregation, how specific protein domains influence these aggregates in Huntington's disease, and how pathological alpha-synuclein aggregates nucleate in a reductionist system of Parkinson's disease.

As a Roche Postdoctoral Fellow in Henning Stahlberg's lab at the Biozentrum University of Basel, co-mentored by Matthias Lauer and Markus Britschgi at Roche Innovation Center Basel, Shahmoradian and her colleagues discovered that membranes and lipidic material are central to Lewy bodies and Lewy neurites in Parkinson's disease. These findings, validated through various biophysical and biochemical techniques, led to a major reevaluation of these pathological structures that emphasizes alpha-synuclein-lipid interactions. This research has informed the development of more accurate cellular models and strategies for small molecule design in imaging and therapy.

Currently, the Shahmoradian lab uses advanced imaging techniques, including cryo-ET and correlative light and electron microscopy (CLEM), to investigate how proteins prone to aggregation and their interactions with lipids affect processes at the synapse and endoplasmic reticulum (ER) in health and disease. Her lab aims to understand the macromolecular basis of protein aggregation and membrane remodeling in neuronal diseases within functional neuronal systems. They also innovate by developing new interfaces and technologies to advance EM-based techniques.

Research Interest

Cryo-electron tomography
Micro and Nanoengineering
Neurodegeneration
Protein aggregation

Publications

Featured Publications

Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes.: Shahmoradian SH, Lewis AJ, Genoud C, Hench J, Moors TE, Navarro PP, Castaño-Díez D, Schweighauser G, Graff-Meyer A, Goldie KN, Sütterlin R, Huisman E, Ingrassia A, Gier Y, Rozemuller AJM, Wang J, Paepe A, Erny J, Staempfli A, Hoernschemeyer J, Großerüschkamp F, Niedieker D, El-Mashtoly SF, Quadri M, Van IJcken WFJ, Bonifati V, Gerwert K, Bohrmann B, Frank S, Britschgi M, Stahlberg H, Van de Berg WDJ, Lauer ME, Nat Neurosci 2019 07 22 7 1099-1109
Three-Dimensional Imaging of Biological Tissue by Cryo X-Ray Ptychography.: Shahmoradian SH, Tsai EHR, Diaz A, Guizar-Sicairos M, Raabe J, Spycher L, Britschgi M, Ruf A, Stahlberg H, Holler M, Sci Rep 2017 07 7 1 6291
TRiC's tricks inhibit huntingtin aggregation.: Shahmoradian SH, Galaz-Montoya JG, Schmid MF, Cong Y, Ma B, Spiess C, Frydman J, Ludtke SJ, Chiu W, Elife 2013 Jul 2 e00710
Supramolecular non-amyloid intermediates in the early stages of a-synuclein aggregation.: Fauerbach JA, Yushchenko DA, Shahmoradian SH, Chiu W, Jovin TM, Jares-Erijman EA, Biophys J 2012 Mar 102 5 1127-36
Docking for Molecules That Bind in a Symmetric Stack with SymDOCK.: Smith MS, Knight IS, Kormos RC, Pepe JG, Kunach P, Diamond MI, Shahmoradian SH, Irwin JJ, DeGrado WF, Shoichet BK, J Chem Inf Model 2024 Jan 64 2 425-434
Docking for molecules that bind in a symmetric stack with SymDOCK.: Smith MS, Knight IS, Kormos RC, Pepe JG, Kunach P, Diamond MI, Shahmoradian SH, Irwin JJ, DeGrado WF, Shoichet BK, bioRxiv 2023 Oct
Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.: Kunach P, Vaquer-Alicea J, Smith MS, Hopewell R, Monistrol J, Moquin L, Therriault J, Tissot C, Rahmouni N, Massarweh G, Soucy JP, Guiot MC, Shoichet BK, Rosa-Neto P, Diamond MI, Shahmoradian SH, bioRxiv 2023 Sep
Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates.: Galaz-Montoya JG, Shahmoradian SH, Shen K, Frydman J, Chiu W, Commun Biol 2021 07 4 1 849
A Compartmentalized Neuronal Cell-Culture Platform Compatible With Cryo-Fixation by High-Pressure Freezing for Ultrastructural Imaging.: Tran HT, Lucas MS, Ishikawa T, Shahmoradian SH, Padeste C, Front Neurosci 2021 15 726763
A lathe system for micrometre-sized cylindrical sample preparation at room and cryogenic temperatures.: Holler M, Ihli J, Tsai EHR, Nudelman F, Verezhak M, van de Berg WDJ, Shahmoradian SH, J Synchrotron Radiat 2020 Mar 27 Pt 2 472-476