About

David Goldstein holds a joint position in the Department of Linguistics and the Program in Indo-European Studies at UCLA, with a courtesy appointment in the Department of Classics. His research focuses on the intersection of language change and linguistic theory, specifically examining syntactic, morphosyntactic, and semantic change among the Indo-European languages. He is a member of the 2021 cohort of Guggenheim Fellows. Goldstein's educational background includes a Ph.D. from the University of California, Berkeley, earned in 2010, an M.A. from Berkeley in 2004, an M.Phil. from the University of Oxford's Corpus Christi College in 2002, and a B.A. from Amherst College in 2000.

Research topics

• Computer Science
• Artificial Intelligence
• Natural Language Processing
• Sociology
• Mathematics
• Machine Learning
• Physics
• Linguistics
• Philosophy
• Algorithm
• Geology
• Biology
• Chemistry
• Demography
• Genealogy
• Econometrics
• Paleontology
• Statistics
• Astrobiology
• Mathematical optimization
• History

Selected publications

• Shaping the future of clinical trials through strategic foresight

  Clinical Trials · 2026-02-26

  articleOpen access

  BACKGROUND/AIMS: Global megatrends, including population growth, interconnectedness and artificial intelligence, are already shaping the clinical trials industry, and will do so for decades to come. Innovations from technology companies, greater collaboration with patients and caregivers, and increased diversity in clinical trials could transform clinical trials of the future. However, the industry has typically been slow to adopt new technologies, and certain barriers could stifle innovation and allow health inequalities to persist. Our aim was to explore the trends shaping clinical trials and identify initiatives that can be started now to move toward a future where patients are actively involved in clinical trial design and decision-making, and technologies like artificial intelligence are integrated responsibly and ethically into clinical trials. METHODS: We used strategic foresight methodology to explore the trends that will shape the future of clinical trials and how the trajectory of these trends could lead to different future scenarios We then identified initiatives that could help us move toward our desired scenario. RESULTS: We identified four possible scenarios for the future of clinical trials based on two key trends: data sharing and adaptation of regulatory frameworks. While the future will see collection of large amounts of data from different sources, such as databases and wearable devices, their usefulness could be limited if data remain in silos, limited by strict regulations and a lack of trust in data privacy. Alternatively, data may be integrated more efficiently into clinical trials if regulators adapt proactively to new technologies and patients are empowered to take control over their data, for example. We identified initiatives that can be started now to achieve our vision. Pharmaceutical companies, academic researchers, non-governmental organizations (including patient organizations), regulatory authorities, policymakers, technology companies and innovative service providers must join forces and work on initiatives to integrate technology into trials, enable data sharing, harmonize regulations across regions, co-design trials with patients and caregivers, strengthen decentralized trial capabilities and promote diversity in trials. CONCLUSION: Through a collaborative cross-industry effort that prioritizes proactive patient involvement and responsible use of technology, we can shape a clinical trial ecosystem that is inclusive, ethical and ready for the future. We urge all stakeholders to act now on these initiatives to positively influence the future of clinical trials.

  PublisherDOI

• Topography formation driven by sublimation of pure species on icy airless worlds

  Icarus · 2024-03-11 · 2 citations

  article
  PublisherDOI

• Data from Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses

  2023-03-30

  preprintOpen access

  <div>Abstract<p>The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out <i>TOP1</i> is lethal in metazoans. To reveal the functions of human Top1, we have generated stable Top1 small interfering RNA (siRNA) cell lines from colon and breast carcinomas (HCT116-siTop1 and MCF-7-siTop1, respectively). In those clones, Top1 is reduced ∼5-fold and Top2α compensates for Top1 deficiency. A prominent feature of the siTop1 cells is genomic instability, with chromosomal aberrations and histone γ-H2AX foci associated with replication defects. siTop1 cells also show rDNA and nucleolar alterations and increased nuclear volume. Genome-wide transcription profiling revealed 55 genes with consistent changes in siTop1 cells. Among them, asparagine synthetase (ASNS) expression was reduced in siTop1 cells and in cells with transient Top1 down-regulation. Conversely, Top1 complementation increased ASNS, indicating a causal link between Top1 and ASNS expression. Correspondingly, pharmacologic profiling showed l-asparaginase hypersensitivity in the siTop1 cells. Resistance to camptothecin, indenoisoquinoline, aphidicolin, hydroxyurea, and staurosporine and hypersensitivity to etoposide and actinomycin D show that Top1, in addition to being the target of camptothecins, also regulates DNA replication, rDNA stability, and apoptosis. Overall, our studies show the pleiotropic nature of human Top1 activities. In addition to its classic DNA nicking-closing functions, Top1 plays critical nonclassic roles in genomic stability, gene-specific transcription, and response to various anticancer agents. The reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function. [Cancer Res 2007;67(18):8752–61]</p></div>

  PublisherDOI

• Supplemental Table S3 from The NCI-60 Methylome and Its Integration into CellMiner

  2023-03-31

  preprintOpen access

  <p>Linear regression analysis of 15,798 genes with with transcript expression, DNA methylation, and DNA copy number data available.</p>

  PublisherDOI

• Supplemental Table S1 from The NCI-60 Methylome and Its Integration into CellMiner

  2023-03-31

  preprintOpen access

  <p>128,394 probes used for the determination of gene methylation levels.</p>

  PublisherDOI

• The Plumes and Atmosphere of Io

  Astrophysics and space science library · 2023-01-01 · 8 citations

  book-chapter
  PublisherDOI

• Data from Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses

  2023-03-30

  preprintOpen access

  <div>Abstract<p>The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out <i>TOP1</i> is lethal in metazoans. To reveal the functions of human Top1, we have generated stable Top1 small interfering RNA (siRNA) cell lines from colon and breast carcinomas (HCT116-siTop1 and MCF-7-siTop1, respectively). In those clones, Top1 is reduced ∼5-fold and Top2α compensates for Top1 deficiency. A prominent feature of the siTop1 cells is genomic instability, with chromosomal aberrations and histone γ-H2AX foci associated with replication defects. siTop1 cells also show rDNA and nucleolar alterations and increased nuclear volume. Genome-wide transcription profiling revealed 55 genes with consistent changes in siTop1 cells. Among them, asparagine synthetase (ASNS) expression was reduced in siTop1 cells and in cells with transient Top1 down-regulation. Conversely, Top1 complementation increased ASNS, indicating a causal link between Top1 and ASNS expression. Correspondingly, pharmacologic profiling showed l-asparaginase hypersensitivity in the siTop1 cells. Resistance to camptothecin, indenoisoquinoline, aphidicolin, hydroxyurea, and staurosporine and hypersensitivity to etoposide and actinomycin D show that Top1, in addition to being the target of camptothecins, also regulates DNA replication, rDNA stability, and apoptosis. Overall, our studies show the pleiotropic nature of human Top1 activities. In addition to its classic DNA nicking-closing functions, Top1 plays critical nonclassic roles in genomic stability, gene-specific transcription, and response to various anticancer agents. The reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function. [Cancer Res 2007;67(18):8752–61]</p></div>

  PublisherDOI

• Supplemental Figure S2 from The NCI-60 Methylome and Its Integration into CellMiner

  2023-03-31

  preprintOpen access

  <p>Relationship between methylation and lack of SLFN11 and MGMT expression in the NCI-60.</p>

  PublisherDOI

• Supplementary Table 1 from Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses

  2023-03-30

  supplementary-materialsOpen access

  Supplementary Table 1 from Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses

  PublisherOA PDFDOI

• Data from The NCI-60 Methylome and Its Integration into CellMiner

  2023-03-31

  preprintOpen access

  <div>Abstract<p>A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (∼21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and miRNA transcripts, DNA copy number, and protein levels. Here, we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2.0 (<a href="https://discover.nci.nih.gov/cellminer" target="_blank">https://discover.nci.nih.gov/cellminer</a>). Among new insights, transcript versus DNA methylation correlations revealed the epithelial/mesenchymal gene functional category as being influenced most heavily by methylation. DNA methylation and copy number integration with transcript levels yielded an assessment of their relative influence for 15,798 genes, including tumor suppressor, mitochondrial, and mismatch repair genes. Four forms of molecular data were combined, providing rationale for microsatellite instability for 8 of the 9 cell lines in which it occurred. Individual cell line analyses showed global methylome patterns with overall methylation levels ranging from 17% to 84%. A six-gene model, including <i>PARP1, EP300, KDM5C, SMARCB1</i>, and <i>UHRF1</i> matched this pattern. In addition, promoter methylation of two translationally relevant genes, Schlafen 11 (<i>SLFN11</i>) and methylguanine methyltransferase (<i>MGMT</i>), served as indicators of therapeutic resistance or susceptibility, respectively. Overall, our database provides a resource of pharmacologic data that can reinforce known therapeutic strategies and identify novel drugs and drug targets across multiple cancer types. <i>Cancer Res; 77(3); 601–12. ©2016 AACR</i>.</p></div>

  PublisherDOI

Recent grants

• CCR Sequencing Facility

  NIH · $68.2M

• NIH Grant R29CA063044

  NIH · $432k · 1999

• Roles and regulation of aqua/glyceroporins in a freeze tolerant amphibian

  NSF · $562k · 2011–2016

Frequent coauthors

• J-F. Arguin

  86 shared

• E. J. Jeon

  Institute for Basic Science

  83 shared

• A. Warburton

  McGill University

  80 shared

• G. Latino

  Istituto Nazionale di Fisica Nucleare, Sezione di Firenze

  79 shared

• A. Cerri

  77 shared

• D. MacQueen

  University of Alberta

  73 shared

• K. K. Joo

  69 shared

• D. J. Kong

  Kumamoto University

  64 shared

Education

• Ph.D., Physics and Astronomy

  University of California Los Angeles

  2004

Awards & honors

• 2021 cohort of Guggenheim Fellows