Sarah Shahmoradian, Ph.D.

Assistant Professor

Schools: Medical School | Graduate School
Departments: Center for Alzheimer's and Neurodegenerative Diseases | Biophysics | Peter O'Donnell Jr. Brain Institute
Graduate Programs: Genetics, Development and Disease, Molecular Biophysics, Neuroscience

Biography

Sarah Shahmoradian, Ph.D., is an Assistant Professor of Biophysics in the Center for Alzheimer’s and Neurodegenerative Diseases at the Peter O’Donnell Jr. Brain Institute at UT Southwestern Medical Center. Her lab studies neurodegenerative disease at the scale where molecular damage becomes cellular pathology, examining how aggregation-prone proteins interact with lipid membranes, organelles, synapses, and the endoplasmic reticulum inside intact cells and tissues.

Raised in Richmond, Virginia, Dr. Shahmoradian earned her Ph.D. in Molecular Physiology and Biophysics from Baylor College of Medicine in 2013 with Wah Chiu, now at Stanford University. Her doctoral work used cryo-electron microscopy and cryo-electron tomography to define mechanisms that govern protein aggregation in Huntington’s and Parkinson’s disease, including TRiC/CCT-mediated suppression of Huntingtin aggregation and alpha-synuclein nucleation in model systems.

As a Roche Postdoctoral Fellow at the Biozentrum, University of Basel, with collaborators at Roche Innovation Center Basel, Dr. Shahmoradian helped shift the field’s view of Parkinson’s disease Lewy pathology. Her work showed that Lewy bodies and Lewy neurites are not simple amyloid deposits, but complex cellular lesions enriched in membranes, organelles, and lipidic material. These findings placed alpha-synuclein membrane interactions and aggregate-cellular interfaces at the center of disease mechanism, with implications for disease modeling, PET imaging probe development, and therapeutic design.

Since joining UT Southwestern in 2021, the Shahmoradian Lab has advanced cryo-EM, correlative cryo-electron tomography, CLEM, and quantitative microscopy to visualize disease-relevant structures in preserved neuronal systems. By retaining fragile membranes, molecular contacts, and cellular architecture that can be disrupted during purification or chemical processing, the lab connects molecular structure to neuronal context. Its long-term goal is to define mechanisms of protein aggregation and membrane remodeling that inform imaging and therapeutic strategies for neurodegenerative disease.

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
TorsinA is essential for neuronal nuclear pore complex localization and maturation.: Kim S, Phan S, Tran HT, Shaw TR, Shahmoradian SH, Ellisman MH, Veatch SL, Barmada SJ, Pappas SS, Dauer WT, Nat Cell Biol 2024 Aug
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