https://www.fitzpatrick-lab.org/research-projects daily 0.75 2021-02-15 https://www.fitzpatrick-lab.org/news daily 0.75 2024-01-25 https://www.fitzpatrick-lab.org/news/congratulations-to-andrew-chang-for-winning-the-bridges-amp-sturtevant-prize-in-biological-sciences monthly 0.5 2024-01-25 https://www.fitzpatrick-lab.org/news/fitzpatrick-lab-amp-collaborators-publish-in-cell monthly 0.5 2024-01-25 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/b825c35d-b2ba-44cc-8e87-0076322ad239/lrp2.jpg News - Fitzpatrick, Shapiro, Barasch Labs publish in Cell - Structures of LRP2 reveal a molecular machine for endocytosis The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily. https://www.fitzpatrick-lab.org/news/m0tnkemzwbdknpma8pkiwpzkifafwd monthly 0.5 2024-01-25 https://www.fitzpatrick-lab.org/news/fitzpatrick-lab-team-publishes-in-cell monthly 0.5 2024-01-25 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/286d16cb-dd03-4009-950b-5e32bcf127ff/fx1_lrg.jpg News - Fitzpatrick Lab publishes in Cell - Discovery made by Fitzpatrick Lab team reveals that TMEM106B, a protein normally involved in clearing cells of molecular debris, can clump into fibrils, potentially hobbling cells. Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration. https://www.fitzpatrick-lab.org/news/christina-lee-and-xinyu-xiang-join-stanford-biophysics monthly 0.5 2021-09-04 https://www.fitzpatrick-lab.org/news/fitzpatrick-lab-awarded-czi-visual-proteomics-grant monthly 0.5 2021-09-04 https://www.fitzpatrick-lab.org/news/f2h8hs0nt6hd2tboonuvdq306n3jc3 monthly 0.5 2024-01-25 https://www.fitzpatrick-lab.org/news/drfitzpatrick-interviewed-by-scientific-american monthly 0.5 2021-09-04 https://www.fitzpatrick-lab.org/news/blog-post-four-tjsz2 monthly 0.5 2021-09-04 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613848502257-90QSFEMVNWRSIW91R2Y2/Tamta+Happy+News.jpg News - Fitzpatrick Lab undergrads publish in Cell - The Fitzpatrick Lab is immensely proud to share that our two undergraduate research fellows, Tamta Arakhamia and Christina E. Lee, have published as co-first authors in Cell! The study, published today in Cell, employed two complementary techniques to map the structure of tau and decipher the effects of additional molecules, called post-translational modifications (PTMs), on its surface. These new structural insights could accelerate the fight against neurodegenerative diseases, by helping researchers identify new biomarkers that detect these disorders before symptoms arise and design new drugs that target specific PTMs, preventing the onset of disease before it wreaks havoc on the brain. Tamta Arakhamia and Christina L https://www.fitzpatrick-lab.org/news/m5p1euckkal7bg30f8kodowgj68l5q monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614808832802-1CEYHFHAP4XCI24FHDYM/CLEM+News.jpeg News - Fitzpatrick Lab CLEM is installed - Leica installed and trained the lab on how to use our new CLEM, acquiring nice z-stacks of cultured neurons in vitreous ice. Leica installed and trained the lab on how to use our new CLEM, acquiring nice z-stacks of cultured neurons in vitreous ice. https://www.fitzpatrick-lab.org/news/86b20zwsoa6zrogmombmjzg1an1jvw monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809108364-R7G8MV5FYEODBYFQSCA9/Amino+Acids+News.jpg News - Fitzpatrick Lab visualizes amino acids in atomic detail using cryo-EM! https://www.fitzpatrick-lab.org/news/7y6mysu3c6e4td81pusqwxp73t89f9 monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809221265-3XRJ09IB6KI0UV0UAHJG/Christina+Oxford+Happy.jpg News - Christina Lee joins the University of Oxford! - Many congratulations to our research fellow and Laidlaw Scholar Christina Lee for securing a summer research position at the prestigious University of Oxford, England. Christina will be working in the Benesch Lab at Oxford, doing research in the field of mass spectrometry. We are excited for her accomplishment and new research findings she will bring to the Fitzpatrick Lab upon her return. https://www.fitzpatrick-lab.org/news/x6xd336asd1fxh48wsc79mjvblmu0p monthly 0.5 2021-09-04 https://www.fitzpatrick-lab.org/news/sphdha6ca8zzc7av7j6w6dcsporz0b monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809428986-OY0PH8YKRUUYW4NHWFVT/Aquilos+News.png News - Fitzpatrick Lab acquires Aquilos FIB SEM - The Aquilos Cryo-FIB is the first cryo-DualBeam (focused ion beam/scanning electron microscope) system dedicated to preparation of frozen, thin lamella samples from biological specimens for high-resolution tomographic imaging in a cryo-transmission electron microscope (cryo-TEM). Cryo-electron tomography’s ability to visualize structures in their native context allows researchers to observe functional relationships and interactions with other components in the cellular environment. This technique will prove crucial in better understanding neuroscience on a molecular level. https://www.fitzpatrick-lab.org/news/bwtu4d3vj6h938b0k6qn84j6n6lwa0 monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809521136-APYG90VL1UGAAGPBRGMA/KRIOS+News.jpg News - Zuckerman Krios beam is on - Members of the Fitzpatrick Lab will now have access to the new Titan Krios microscope at the Zuckerman Instiute. The KRIOS boasts a Gatan BioQuantum energy filter and K3 Summit direct electron detector. The next-generation K3 direct detection camera is optimized for the most demanding low-dose applications in both life science and materials science research, proving to be a significant asset to the Zuckerman KRIOS system. We are excited to begin imaging on this state-of-the-art microscope! https://www.fitzpatrick-lab.org/news/d9yaeug3b2cdxcxhnk3q66nhlcyjg5 monthly 0.5 2021-05-31 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809648062-R34XEF0M96H7WDFHM0LQ/curealzlogo.png News - Fitzpatrick Lab supported by Cure Alzheimer's Fund https://www.fitzpatrick-lab.org/news/nqrfqi8wsz1p3n1n0uwjg4k8cm1wkm monthly 0.5 2021-05-31 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809788023-YG2NUM6Q7K9SKLAAQ6VB/AFTDLogo.jpg News - Fitzpatrick Lab awarded FTD Biomarkers Initiative Award https://www.fitzpatrick-lab.org/news/txgb4fp7pwac6uiriqw9u6y7finutv monthly 0.5 2021-03-03 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809838281-M0S1Q3CIXEASZWQVLNLD/Christina+Happy+News.jpeg News - Christina Lee presents her research on tau imaging in Alzheimer’s disease brain - Christina Lee, Laidlaw Scholar and Research Assistant, presents her exciting advances in imaging tau inclusions in Alzheimer’s disease postmortem brain tissue at the Laidlaw Scholar’s symposium in Lerner Hall. https://www.fitzpatrick-lab.org/news/qycv0skt7y7fanx242345ho0bpcr5x monthly 0.5 2021-09-04 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614809912381-F4XG8G2WQM6EIDNYF265/Fitzpatrick-Hero-News+Photo.jpg News - Dr. Anthony Fitzpatrick and Collaborators Awarded $7.8M to Identify New Targets Against Brain Disease Using cryo-electron microscopy (cryo-EM), Dr. Fitzpatrick’s team will focus their efforts primarily on tau tangles, clumps of misfolded tau protein that have been implicated in a host of diseases, most notably Alzheimer’s disease and chronic traumatic encephalopathy, or CTE. By reconstructing the structure of tau tangles in these diseases — atom by atom — the researchers hope to gain new insight into how tangles form, how they grow and how they drive disease progression. These findings will enable researchers to design drug molecules that prevent tangle buildup. They will also aid development of new biomarkers that detect the disease early, before symptoms arise. Dr. Fitzpatrick will serve as lead principal investigator of this five-year project, which will be administered by the National Institute of Neurological Disorders and Stroke (NINDS). He will be joined by Leonard Petrucelli, PhD, Chair and Professor of Neuroscience at Mayo Clinic’s Florida campus, and Judith Steen, PhD, Associate Professor of Neurobiology at Harvard University and Boston Children’s Hospital. https://www.fitzpatrick-lab.org/news/blog-post-three-ll66r monthly 0.5 2021-09-04 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614810060852-4RWBU18XA5H8PCGNKUJP/Popular+Mechanics.png News - Dr. Anthony Fitzpatrick featured in Popular Mechanics - The Heroes of Science Who are Unlocking The Brain Popular Mechanics features stories of indefatigable researchers, heroic engineers, and champions of neuroscience who are finally turning the corner in the effort to understand, heal, and improve the human brain. https://www.fitzpatrick-lab.org/news/blog-post-two-slf99 monthly 0.5 2021-05-31 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614810336731-ACYYODO3LS2BJPFAX914/dana3.png News - Fitzpatrick Lab awarded Dana Foundation David Mahoney Neuroimaging grant - The Fitzpatrick lab is using cryo-EM of postmortem tissue from people with neurodegenerative diseases to differentiate each disease’s molecular signature leading to improved diagnoses of patients through Positron Emission Tomography (PET) imaging by developing PET tracers that bind to the molecules involved in each disease. PET could then be used to differentiate, diagnose, and monitor progression of each neurodegenerative disease. https://www.fitzpatrick-lab.org/news/blog-post-one-s7jdp monthly 0.5 2021-05-31 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613849526589-70O4YGDX9QR5CI4AU833/Thermo_Fisher_young_investigator_shield_500x500_0.jpg News - Dr. Anthony Fitzpatrick receives the Young Investigator Life Sciences Award - Thermo Fisher Scientific's Young Investigator Award is presented in recognition of a researcher who has recently published work in a scientific journal and whose research meets the criteria of having significant biological relevance, a high impact on the research community, transparency in materials and methodology for peers, and exemplifies innovation in utilizing a pre-established or new process or methodology in the field of life science research. https://www.fitzpatrick-lab.org/home daily 1.0 2026-02-01 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/d2862b1a-1691-4b41-8373-7b2e719944f2/Screen+Shot+2022-06-28+at+4.03.17+PM.png Home Homotypic fibrillization of TMEM106B Cryo-EM and mass spectrometry-based proteomics of insoluble amyloid fibrils derived from postmortem human brains afflicted with diverse neurodegenerative diseases reveals widespread fibrillization of an endolysosomal membrane protein, TMEM106B, pointing toward a potentially pathogenic commonality between distinct proteinopathies. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614807670804-3KIL71Q3XO8C1P3K66RO/nature+cover-1.jpg Home - Structures of Human Brain-Derived Amyloid Fibrils Many debilitating human disorders, including Alzheimer’s and Parkinson’s diseases, are associated with the conversion of normally soluble functional proteins into highly ordered aggregates known as amyloid fibrils. Determining the atomic structures of these filamentous aggregates is crucial to understanding their formation, clearance and spreading in the human body. The Fitzpatrick Lab uses cryo-EM to solve the structures of filaments isolated from postmortem brain tissue of patients – Patient-Based Structural Biology – with a range of neurological disorders to elucidate the molecular and structural basis of neurodegeneration, enabling structure-based drug design and the development of biomarkers for early detection. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1628541574415-6IGZAFD7SRY7PAVGEB0K/czi2.png Home - Fitzpatrick Lab awarded CZI Visual Proteomics Grant The Chan Zuckerberg Initiative (CZI) announced nearly $28 million in grants to support technology developments that will allow researchers to see the inner workings of cells at near-atomic resolution through next-generation electron microscopy. The Frontiers of Imaging initiative, part of CZI’s broader Imaging program, supports the development of disruptive imaging technologies that connect biological scales across organs, cells, and proteins, allowing researchers to directly visualize biological processes at the necessary resolution and context to obtain a mechanistic understanding of health and disease. The Fitzpatrick lab will develop a pulsed ponderomotive phase plate that allows in-focus phase contrast of cryo-EM specimens. By focusing a pulsed laser to intersect the post-specimen electron beam, the ponderomotive potential of the focused laser crossover produces a scattering-angle-dependent phase shift in the electrons, resulting in a highly tunable contrast transfer function, with significantly enhanced contrast of the cells under inspection. This powerful approach to boosting contrast in cellular cryo-electron tomograms has the potential to revolutionize our understanding of biology by mapping cell atlases in unprecedented detail. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613432586867-9CCAKRT2BJEILMU82XDG/Tamta+Happy+News.jpg Home - Fitzpatrick Lab undergraduates publish in Cell The Fitzpatrick Lab is immensely proud to share that our two undergraduate research fellows, Tamta Arakhamia and Christina E. Lee, have published as co-first authors in Cell! The study, published today in Cell, employed two complementary techniques to map the structure of tau and decipher the effects of additional molecules, called post-translational modifications (PTMs), on its surface. These new structural insights could accelerate the fight against neurodegenerative diseases, by helping researchers identify new biomarkers that detect these disorders before symptoms arise and design new drugs that target specific PTMs, preventing the onset of disease before it wreaks havoc on the brain. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613432898256-VDRNWSV5C5O58OTMSJP1/Fitzpatrick-Hero-News+Photo.jpg Home - Dr. Anthony Fitzpatrick and Collaborators Awarded $8.8M to Identify New Targets Against Brain Disease Using cryo-electron microscopy (cryo-EM), Dr. Fitzpatrick’s team will focus their efforts primarily on tau tangles, clumps of misfolded tau protein that have been implicated in a host of diseases, most notably Alzheimer’s disease and chronic traumatic encephalopathy, or CTE. By reconstructing the structure of tau tangles in these diseases — atom by atom — the researchers hope to gain new insight into how tangles form, how they grow and how they drive disease progression. These findings will enable researchers to design drug molecules that prevent tangle buildup. They will also aid development of new biomarkers that detect the disease early, before symptoms arise. Dr. Fitzpatrick will serve as lead principal investigator of this five-year project, which will be administered by the National Institute of Neurological Disorders and Stroke (NINDS). He will be joined by Leonard Petrucelli, PhD, Chair and Professor of Neuroscience at Mayo Clinic’s Florida campus, and Judith Steen, PhD, Associate Professor of Neurobiology at Harvard University and Boston Children’s Hospital. https://www.fitzpatrick-lab.org/tomography daily 0.75 2026-02-01 https://www.fitzpatrick-lab.org/people daily 0.75 2024-01-24 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/c995fa91-6055-4bd5-a9b7-d51879cbe2af/Tamta.jpeg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1623896907421-Y6HC52I3RSZ7XV26MX2M/IMG_7459.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1623896584188-16PXT3CMZYB6OP1SY4TZ/alinew.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/7a170685-c4b7-4247-bd2d-691ab1adb1db/TOM06383.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/aa55dde1-4e37-443d-a364-80fece5a6dcb/SilviaToderos.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/7a91782d-bdb2-404f-be58-8b1742f04ce5/WillMallen.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/6e7a8d7b-3671-4f40-a27a-a827b404b884/PriyankaMatthews.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/092d1dc3-b899-4c94-a1d9-137ab88f1013/DanielDu.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/31cb4905-2228-4a15-a67a-6968867cc63e/MSimjanoska_Headshot.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/a68e141d-3ed3-431e-9630-ae31b233ce19/YukiOgawa.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/fcaf01d4-959b-455c-8b61-dbe3be9fe801/IMG_1729.jpg Lab Members https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613507953831-KHPPVI5IKF5O8BZQ4YJE/linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+linas+urnavicius+Rockefeller+University+Tarun+Kapoor+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick+linas+urnavicius+Columbia+University+Anthony+Fitzpatrick Lab Members - Anthony W.P. Fitzpatrick Principal Investigator Anthony Fitzpatrick is an Assistant Professor of Biochemistry and Molecular Biophysics at the Zuckerman Institute, Columbia University, New York, USA. Previously, he was a Marie Curie International Outgoing Fellow at the California Institute of Technology (2012-2015) and the Laboratory of Molecular Biology, University of Cambridge (2015-2017). He has a biophysics background (Ph.D. with Professor Sir Christopher M. Dobson, University of Cambridge) and undertook postdoctoral training with Professors Ahmed H. Zewail (Nobel Laureate), Sjors Scheres, and Michel Goedert. https://www.fitzpatrick-lab.org/pulsed-laser-phase-plate daily 0.75 2021-05-29 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1622325790947-OB52YY2RYR31B2KJ9INJ/UEM.png Pulsed Laser Phase Plate Schematic of an ultrafast electron microscope for improved cryo-electron tomography contrast by phase-shifting a pulsed probe electron beam through 90º via the ponderomotive potential of the focused laser crossover of an intersecting pulsed laser beam. https://www.fitzpatrick-lab.org/publications daily 0.75 2024-01-25 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/cd44f873-e5c6-40a2-ac17-d590a86ac868/Screenshot+from+2024-01-23+13-41-07.png Publications - Beenken, A., Cerutti, G., Brasch, J., Guo, Y., Sheng, Z., Erdjument-Bromage, H., Aziz, Z., Robbins-Juarez, S. Y., Chavez, E. Y., Ahlsen, G., Katsamba, P. S., Neubert, T. A., Fitzpatrick, A. W. P., Barasch, J., & Shapiro, L.. Structures of LRP2 reveal a molecular machine for endocytosis. Cell, 186(4), 821–836.e13. February 2023 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/0d4e3e1b-31b0-446d-8b84-2c0d7b568cc8/DuPaper.jpg Publications - Du, D. X., Fitzpatrick, A. W. P. Design of an ultrafast pulsed ponderomotive phase plate for cryo-electron tomography. Cell reports methods, 3(1), 100387. January 2023 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1c1949a9-94f5-43cd-b0af-8e595024237f/Screen+Shot+2022-06-28+at+4.03.17+PM.png Publications - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614734968867-46NBOWGU1CM7P8ED27UW/Fitzpatrick_TauPTMcover_FinalHighRes.png Publications T. Arakhamia*, C.E. Lee*, Y. Carlomagno*, D.M. Duong, S.R. Kundinger, K. Wang, D. Williams, M. DeTure, D.W. Dickson, C.N. Cook, N.T. Seyfried, L. Petrucelli, A.W.P. Fitzpatrick. *These authors contributed equally to this work. Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell. 180 (4), 633-644. e12. February 2020 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614734232765-67E4RG6LQFJDIQ9XM587/nature+cover-1.jpg Publications A.W.P. Fitzpatrick, B. Falcon, S. He, G.N. Murshudov, A.G. Murzin, H.J. Garringer, R.A. Crowther, B. Ghetti, M. Goedert, S.H.W. Scheres. Cryo-EM structures of tau filaments from Alzheimer's disease. Nature. 547(7662):185-190. July 2017 https://www.fitzpatrick-lab.org/videos daily 0.75 2024-01-23 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/e1752010-be0d-454b-b43a-22e5da278ff2/lrp2.gif https://www.fitzpatrick-lab.org/new-page daily 0.75 2021-06-16 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1622418107262-D1OY1SKBK0ZANX8FG50N/Figure+7+publication.png Images - Make it stand out Proposed Structure-Based Model of How Interplay between PTMs Influences Tau Filament Structure. Based on our cryo-EM maps and MS PTM mapping onto atomic models, we conclude that ubiquitination of tau can mediate inter-protofilament interfaces in the doublet CBD fibril and straight filament from AD. If sites on tau favoring the formation of doublet fibrils in CBD (K353) or straight filaments in AD (K311 and K317/321) are acetylated, or ubiquitinated with low occupancy, this inter-protofilament interface is less likely to form. The singlet fibril in CBD does not bind to a second protofilament, and paired helical filaments in AD have structures that do not require mediation by non-tau components at their inter-protofilament interface. The outcome of this model is that the incorporation of ubiquitin into tau filaments in CBD and AD mediates inter-protofilament packing resulting in distinct ultrastructural polymorphs, tuning the ratio of fibril subtypes in tau inclusions. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1622418208775-5GG1X0S4S873254M8K1R/4D_electron_crystallography_USE.png Images - Make it stand out Structural dynamics by 4D Electron Crystallography / Micro-Electron Diffraction. 4D Images and diffraction patterns of a single crystal are recorded at various tilt-angles using a time-delay tn. Amplitudes from the diffraction patterns are combined with phases from the images and after merging data together from a wide variety of tilt angles, a three-dimensional structure at time-delay tn is generated. This procedure is then repeated for the next time delay, tn+1, by changing the optical path length of the pump beam and recording a tilt series and solving the 3D structure at this later time. The 3D structures solved at multiple time delays can be put together sequentially to form frames of a movie showing the conformational changes of the protein of interest. Image adapted with permission from: Membrane protein structure determination by electron crystallography. I. Ubarretxena-Belandia & D.L. Stokes. Current Opinion in Structural Biology 08/2012; 22(4):520-528. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613851216370-D4OYAO3GYBBVKYT19YFN/Tau_Carousel.png Images Cross-β structure and tau deposits in Alzheimer’s disease brain. From left to right, the illustration shows the Alzheimer's disease brain used for cryo-EM, an electron micrograph of negatively stained filaments with a blue arrow indicating a paired helical filament (PHF) and a green arrow indicating a straight filament (SF), cryo-EM reconstructions of PHFs (blue) and SFs (green) with detailed cross sections, and de novo atomic models of filaments showing C-shaped subunits stacked to form each protofilament, with protofilaments paired into twisted polymorphic fibrils. https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613850222320-I5D2LURP44GLRZQSLMX0/Fibrils1.jpg Images https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613851440021-2BBSH1FYO458R21BJD3Z/Popular+Mechanics.png Images https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613850307271-4Q2AE1NEZXNEKEA8AXLS/nature+cover-1.jpg Images https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1616352058305-PSZEHYCDYLCK7SU3S3WQ/SEM.JPG Images https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613850360695-QV6SAIZTIBYF6J5MM9AU/Fibrils2.jpg Images https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1613851492349-HA6F75D8ZPA54VA8QA6V/Immunohistochemistry.jpg Images https://www.fitzpatrick-lab.org/new-page-1 daily 0.75 2024-01-23 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1614977115148-KOP09WN1WIV94JYVYVJH/boss.jpg Anthony Fitzpatrick https://www.fitzpatrick-lab.org/equipment daily 0.75 2021-05-30 https://images.squarespace-cdn.com/content/v1/602adf0df6b7c4321ae3eb1f/1622417178078-9EAZ0FD2T6619IPBTFST/pipeline.png Equipment - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.fitzpatrick-lab.org/alumni daily 0.75 2024-01-24