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Daniel Southworth, PhD

Title(s)Associate Professor, Institute for Neurodegenerative Diseases
SchoolSchool of Medicine
Address675 Nelson Rising Lane
San Francisco CA 94158
Phone415-502-3775
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    Other Positions
    Title(s)UCSF Weill Institute for Neurosciences


    Collapse Biography 
    Collapse Awards and Honors
    American Heart Association2013  - 2016Top Scientist Development Award
    Alzheimer's Association2012  - 2014New Investigator Award
    University of Michigan2011Biological Sciences Scholar
    American Cancer Society2007  - 2010Postdoctoral Fellowship
    Johns Hopkins University2004Paul Ehrlich Research Award

    Collapse Research 
    Collapse Research Activities and Funding
    The molecular mechanisms of nutrient- and stress-dependent mTORC1 regulation mediated by human Sestrin2.
    NIH R01DK111465Sep 19, 2016 - Aug 31, 2021
    Role: Co-Investigator
    Defining the conformational cycle of nitric oxide synthases
    NIH/NIGMS R01GM110001Sep 1, 2015 - Aug 31, 2020
    Role: Principal Investigator
    Exploration of Molecular Chaperone Complexes During Active Protein Triage
    NIH/NIGMS R01GM109896Jun 1, 2014 - Feb 28, 2018
    Role: Co-Investigator
    Mechanisms of motor neuron toxicity in Kennedy disease
    NIH/NINDS R01NS055746Mar 5, 2007 - Jan 31, 2012
    Role: Co-Principal Investigator
    Mechanisms of Activation for Human Small Heat Shock Proteins: An Integrated Approach
    NIH R01EY017370Apr 1, 2006 - Jun 30, 2020
    Role: Co-Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020 Oct 15. Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D. PMID: 33060197.
      View in: PubMed   Mentions:    Fields:    
    2. Practical Considerations of Using the K3 Camera in CDS Mode for High-resolution and High-throughput Single Particle Cryo-EM. Microscopy and Microanalysis. 2020 Jul 30; 1-1. Ming Sun, Caleigh Azumaya, Eric Tse, Daniel Southworth, Kliment Verba, Adam Frost, Yifan Cheng, David Agard. .
      View in: Publisher Site   Mentions:
    3. Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis. Nat Struct Mol Biol. 2020 05; 27(5):406-416. Lopez KE, Rizo AN, Tse E, Lin J, Scull NW, Thwin AC, Lucius AL, Shorter J, Southworth DR. PMID: 32313240.
      View in: PubMed   Mentions: 5     Fields:    Translation:Cells
    4. Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation. J Biol Chem. 2019 12 13; 294(50):18952-18966. Chen JJ, Nathaniel DL, Raghavan P, Nelson M, Tian R, Tse E, Hong JY, See SK, Mok SA, Hein MY, Southworth DR, Grinberg LT, Gestwicki JE, Leonetti MD, Kampmann M. PMID: 31578281.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansCells
    5. Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity. Life Sci Alliance. 2019 10; 2(5). Lempart J, Tse E, Lauer JA, Ivanova MI, Sutter A, Yoo N, Huettemann P, Southworth D, Jakob U. PMID: 31533964.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    6. Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and a-Synuclein Proteotoxicity. Cell Rep. 2019 08 20; 28(8):2080-2095.e6. Tariq A, Lin J, Jackrel ME, Hesketh CD, Carman PJ, Mack KL, Weitzman R, Gambogi C, Hernandez Murillo OA, Sweeny EA, Gurpinar E, Yokom AL, Gates SN, Yee K, Sudesh S, Stillman J, Rizo AN, Southworth DR, Shorter J. PMID: 31433984.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    7. Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase. Cold Spring Harb Perspect Biol. 2019 08 01; 11(8). Shorter J, Southworth DR. PMID: 30745294.
      View in: PubMed   Mentions: 7     Fields:    Translation:AnimalsCells
    8. Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase. Nat Commun. 2019 06 03; 10(1):2393. Rizo AN, Lin J, Gates SN, Tse E, Bart SM, Castellano LM, DiMaio F, Shorter J, Southworth DR. PMID: 31160557.
      View in: PubMed   Mentions: 11     Fields:    Translation:Cells
    9. Allosteric Regulation of Oligomerization by a B12 Trafficking G-Protein Is Corrupted in Methylmalonic Aciduria. Cell Chem Biol. 2019 07 18; 26(7):960-969.e4. Ruetz M, Campanello GC, McDevitt L, Yokom AL, Yadav PK, Watkins D, Rosenblatt DS, Ohi MD, Southworth DR, Banerjee R. PMID: 31056463.
      View in: PubMed   Mentions:    Fields:    Translation:HumansCells
    10. Chaperone activation and client binding of a 2-cysteine peroxiredoxin. Nat Commun. 2019 02 08; 10(1):659. Teixeira F, Tse E, Castro H, Makepeace KAT, Meinen BA, Borchers CH, Poole LB, Bardwell JC, Tomás AM, Southworth DR, Jakob U. PMID: 30737390.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    11. Cryo-EM Structural Analysis of Neuronal Nitric Oxide Synthase. Biophysical Journal. 2019 Feb 1; 116(3):187a-188a. Thomas H. Pospiech, Yoshihiro Morishima, Yoichi Osawa, Daniel R. Southworth. .
      View in: Publisher Site   Mentions:
    12. Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau. Nat Commun. 2018 11 01; 9(1):4563. Freilich R, Betegon M, Tse E, Mok SA, Julien O, Agard DA, Southworth DR, Takeuchi K, Gestwicki JE. PMID: 30385828.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansCells
    13. Polyphosphate Stabilizes Protein Unfolding Intermediates as Soluble Amyloid-like Oligomers. J Mol Biol. 2018 10 19; 430(21):4195-4208. Yoo NG, Dogra S, Meinen BA, Tse E, Haefliger J, Southworth DR, Gray MJ, Dahl JU, Jakob U. PMID: 30130556.
      View in: PubMed   Mentions: 9     Fields:    Translation:Cells
    14. Chaperone Activity and Dimerization Properties of Hsp90a and Hsp90ß in Glucocorticoid Receptor Activation by the Multiprotein Hsp90/Hsp70-Dependent Chaperone Machinery. Mol Pharmacol. 2018 09; 94(3):984-991. Morishima Y, Mehta RK, Yoshimura M, Lau M, Southworth DR, Lawrence TS, Pratt WB, Nyati MK, Osawa Y. PMID: 29941666.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    15. The full-length cytochrome P450 enzyme CYP102A1 dimerizes at its reductase domains and has flexible heme domains for efficient catalysis. J Biol Chem. 2018 05 18; 293(20):7727-7736. Zhang H, Yokom AL, Cheng S, Su M, Hollenberg PF, Southworth DR, Osawa Y. PMID: 29618513.
      View in: PubMed   Mentions: 3     Fields:    Translation:Cells
    16. X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition. J Biol Chem. 2018 02 16; 293(7):2370-2380. Cesa LC, Shao H, Srinivasan SR, Tse E, Jain C, Zuiderweg ERP, Southworth DR, Mapp AK, Gestwicki JE. PMID: 29255093.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansCells
    17. Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex. J Biol Chem. 2017 10 27; 292(43):17617-17625. Campanello GC, Lofgren M, Yokom AL, Southworth DR, Banerjee R. PMID: 28882898.
      View in: PubMed   Mentions: 2     Fields:    Translation:Cells
    18. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science. 2017 07 21; 357(6348):273-279. Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR. PMID: 28619716.
      View in: PubMed   Mentions: 51     Fields:    Translation:AnimalsCells
    19. Aggregation of Mod5 is affected by tRNA binding with implications for tRNA gene-mediated silencing. FEBS Lett. 2017 06; 591(11):1601-1610. Read DF, Waller TJ, Tse E, Southworth DR, Engelke DR, Smaldino PJ. PMID: 28303570.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    20. BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins. J Mol Biol. 2017 01 06; 429(1):128-141. Rauch JN, Tse E, Freilich R, Mok SA, Makley LN, Southworth DR, Gestwicki JE. PMID: 27884606.
      View in: PubMed   Mentions: 31     Fields:    Translation:HumansCells
    21. Polyphosphate: A Conserved Modifier of Amyloidogenic Processes. Mol Cell. 2016 09 01; 63(5):768-80. Cremers CM, Knoefler D, Gates S, Martin N, Dahl JU, Lempart J, Xie L, Chapman MR, Galvan V, Southworth DR, Jakob U. PMID: 27570072.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimalsCells
    22. Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation. Nat Struct Mol Biol. 2016 09; 23(9):830-7. Yokom AL, Gates SN, Jackrel ME, Mack KL, Su M, Shorter J, Southworth DR. PMID: 27478928.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    23. Architecture and Nucleotide-Dependent Conformational Changes of the Rvb1-Rvb2 AAA+ Complex Revealed by Cryoelectron Microscopy. Structure. 2016 05 03; 24(5):657-666. Ewens CA, Su M, Zhao L, Nano N, Houry WA, Southworth DR. PMID: 27112599.
      View in: PubMed   Mentions: 8     Fields:    Translation:Cells
    24. Single-particle cryo-electron microscopy of macromolecular complexes. Microscopy (Oxf). 2016 Feb; 65(1):9-22. Skiniotis G, Southworth DR. PMID: 26611544.
      View in: PubMed   Mentions: 5     Fields:    Translation:Cells
    25. Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation. Biochemistry. 2015 Dec 08; 54(48):7120-31. Assimon VA, Southworth DR, Gestwicki JE. PMID: 26565746.
      View in: PubMed   Mentions: 26     Fields:    Translation:HumansCells
    26. A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis. Elife. 2015 May 11; 4. Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Southworth DR, Klevit RE. PMID: 25962097.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansCells
    27. Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1. Biochim Biophys Acta. 2015 Jun; 1850(6):1310-8. Byers CE, Barylko B, Ross JA, Southworth DR, James NG, Taylor CA, Wang L, Collins KA, Estrada A, Waung M, Tassin TC, Huber KM, Jameson DM, Albanesi JP. PMID: 25783003.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    28. Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum. Proc Natl Acad Sci U S A. 2015 Feb 17; 112(7):E616-24. Teixeira F, Castro H, Cruz T, Tse E, Koldewey P, Southworth DR, Tomás AM, Jakob U. PMID: 25646478.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    29. The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Mol Cell. 2014 Oct 02; 56(1):116-27. Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, Southworth DR, Schwappach B, Jakob U. PMID: 25242142.
      View in: PubMed   Mentions: 19     Fields:    Translation:AnimalsCells
    30. Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell. 2014 Jun 19; 157(7):1685-97. Kirschke E, Goswami D, Southworth D, Griffin PR, Agard DA. PMID: 24949977.
      View in: PubMed   Mentions: 110     Fields:    Translation:HumansCells
    31. Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain. J Biol Chem. 2014 Jun 13; 289(24):16855-65. Yokom AL, Morishima Y, Lau M, Su M, Glukhova A, Osawa Y, Southworth DR. PMID: 24737326.
      View in: PubMed   Mentions: 20     Fields:    Translation:AnimalsCells
    32. KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated ß-TrCP1 degradation. Neoplasia. 2014 Feb; 16(2):115-28. Shukla S, Allam US, Ahsan A, Chen G, Krishnamurthy PM, Marsh K, Rumschlag M, Shankar S, Whitehead C, Schipper M, Basrur V, Southworth DR, Chinnaiyan AM, Rehemtulla A, Beer DG, Lawrence TS, Nyati MK, Ray D. PMID: 24709419.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    33. The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain. J Biol Chem. 2014 Jan 31; 289(5):2908-17. Connarn JN, Assimon VA, Reed RA, Tse E, Southworth DR, Zuiderweg ER, Gestwicki JE, Sun D. PMID: 24327656.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansCells
    34. The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex. Biochemistry. 2013 Aug 13; 52(32):5354-64. Smith MC, Scaglione KM, Assimon VA, Patury S, Thompson AD, Dickey CA, Southworth DR, Paulson HL, Gestwicki JE, Zuiderweg ER. PMID: 23865999.
      View in: PubMed   Mentions: 25     Fields:    Translation:HumansCells
    35. The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes the closed conformation required for ATP hydrolysis. Protein Sci. 2012 Aug; 21(8):1162-71. Cunningham CN, Southworth DR, Krukenberg KA, Agard DA. PMID: 22653663.
      View in: PubMed   Mentions: 18     Fields:    Translation:HumansAnimalsCells
    36. Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex. Mol Cell. 2011 Jun 24; 42(6):771-81. Southworth DR, Agard DA. PMID: 21700222.
      View in: PubMed   Mentions: 54     Fields:    Translation:HumansCells
    37. High-Q nanomechanics via destructive interference of elastic waves. Phys Rev Lett. 2011 Jan 28; 106(4):047205. Wilson-Rae I, Barton RA, Verbridge SS, Southworth DR, Ilic B, Craighead HG, Parpia JM. PMID: 21405358.
      View in: PubMed   Mentions: 4     Fields:    
    38. Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide. Protein Sci. 2009 Sep; 18(9):1815-27. Krukenberg KA, Böttcher UM, Southworth DR, Agard DA. PMID: 19554567.
      View in: PubMed   Mentions: 26     Fields:    Translation:HumansAnimalsCells
    39. pH-dependent conformational changes in bacterial Hsp90 reveal a Grp94-like conformation at pH 6 that is highly active in suppression of citrate synthase aggregation. J Mol Biol. 2009 Jul 10; 390(2):278-91. Krukenberg KA, Southworth DR, Street TO, Agard DA. PMID: 19427321.
      View in: PubMed   Mentions: 26     Fields:    Translation:Cells
    40. Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle. Mol Cell. 2008 Dec 05; 32(5):631-40. Southworth DR, Agard DA. PMID: 19061638.
      View in: PubMed   Mentions: 92     Fields:    Translation:HumansAnimalsCells
    41. Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome. J Mol Biol. 2007 Dec 07; 374(4):1065-76. Sharma D, Cukras AR, Rogers EJ, Southworth DR, Green R. PMID: 17967466.
      View in: PubMed   Mentions: 41     Fields:    Translation:Cells
    42. Structural Analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements. Cell. 2006 Oct 20; 127(2):329-40. Shiau AK, Harris SF, Southworth DR, Agard DA. PMID: 17055434.
      View in: PubMed   Mentions: 158     Fields:    Translation:Cells
    43. EF-G-independent reactivity of a pre-translocation-state ribosome complex with the aminoacyl tRNA substrate puromycin supports an intermediate (hybrid) state of tRNA binding. RNA. 2004 Jan; 10(1):102-13. Sharma D, Southworth DR, Green R. PMID: 14681589.
      View in: PubMed   Mentions: 43     Fields:    Translation:Cells
    44. Demonstration of the role of the DnaK chaperone system in assembly of 30S ribosomal subunits using a purified in vitro system. RNA. 2003 Dec; 9(12):1418-21. Maki JA, Southworth DR, Culver GM. PMID: 14623997.
      View in: PubMed   Mentions: 10     Fields:    Translation:Cells
    45. Ribosomal translocation: sparsomycin pushes the button. Curr Biol. 2003 Aug 19; 13(16):R652-4. Southworth DR, Green R. PMID: 12932345.
      View in: PubMed   Mentions: 4     Fields:    Translation:Cells
    46. Ribosomal proteins S12 and S13 function as control elements for translocation of the mRNA:tRNA complex. Mol Cell. 2003 Aug; 12(2):321-8. Cukras AR, Southworth DR, Brunelle JL, Culver GM, Green R. PMID: 14536072.
      View in: PubMed   Mentions: 55     Fields:    Translation:Cells
    47. EFG-independent translocation of the mRNA:tRNA complex is promoted by modification of the ribosome with thiol-specific reagents. J Mol Biol. 2002 Dec 06; 324(4):611-23. Southworth DR, Brunelle JL, Green R. PMID: 12460565.
      View in: PubMed   Mentions: 23     Fields:    Translation:Cells
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