Tim MacKenzie

All Publications

• The importance, challenges, and possible solutions for sharing proteomics data while safeguarding individuals' privacy. Molecular & cellular proteomics : MCP Shome, M., MacKenzie, T. M., Subbareddy, S. R., Snyder, M. P. 2024: 100731

  Abstract

  Proteomics data sharing has profound benefits at individual level as well as at community level. While data sharing has increased over the years, mostly due to journal and funding agency requirements, the reluctance of researchers with regards to data sharing is evident as many shares only the bare minimum dataset required to publish an article. In many cases, proper metadata is missing, essentially making the dataset useless. This behavior can be explained by lack of incentives, insufficient awareness, or a lack of clarity surrounding ethical issues. Through adequate training at research institutes, researchers can realize the benefits associated with data sharing and can accelerate the norm of data sharing for the field of proteomics, as has been the standard in genomics for decades. In this article, we have put together various repository options available for proteomics data. We have also added pros and cons of those repositories to facilitate researchers in selecting the repository most suitable for their data submission. It is also important to note that a few types of proteomics data have the potential to re-identify an individual in certain scenarios. In such cases, extra caution should be taken to remove any personal identifiers before sharing on public repositories. Datasets which will be useless without personal identifiers need to be shared in a controlled access repository so that only authorized researchers can access the data and personal identifiers are kept safe.

  View details for DOI 10.1016/j.mcpro.2024.100731

  View details for PubMedID 38331191

• Reverse-ChIP Techniques for Identifying Locus-Specific Proteomes: A Key Tool in Unlocking the Cancer Regulome. Cells MacKenzie, T. M., Cisneros, R., Maynard, R. D., Snyder, M. P. 2023; 12 (14)

  Abstract

  A phenotypic hallmark of cancer is aberrant transcriptional regulation. Transcriptional regulation is controlled by a complicated array of molecular factors, including the presence of transcription factors, the deposition of histone post-translational modifications, and long-range DNA interactions. Determining the molecular identity and function of these various factors is necessary to understand specific aspects of cancer biology and reveal potential therapeutic targets. Regulation of the genome by specific factors is typically studied using chromatin immunoprecipitation followed by sequencing (ChIP-Seq) that identifies genome-wide binding interactions through the use of factor-specific antibodies. A long-standing goal in many laboratories has been the development of a 'reverse-ChIP' approach to identify unknown binding partners at loci of interest. A variety of strategies have been employed to enable the selective biochemical purification of sequence-defined chromatin regions, including single-copy loci, and the subsequent analytical detection of associated proteins. This review covers mass spectrometry techniques that enable quantitative proteomics before providing a survey of approaches toward the development of strategies for the purification of sequence-specific chromatin as a 'reverse-ChIP' technique. A fully realized reverse-ChIP technique holds great potential for identifying cancer-specific targets and the development of personalized therapeutic regimens.

  View details for DOI 10.3390/cells12141860

  View details for PubMedID 37508524

• Students and Postdocs are Needed on the Provost Search Committee MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2023/05/07/from-the-community-students-and-postdocs-are-needed-on-the-provost-search-committee/. 2023
• A Note on Academic Freedom and Institutional Orthodoxy MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2023/06/15/from-the-community-a-note-on-academic-freedom-and-institutional-orthodoxy/. 2023
• Shared Governance MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2023/06/07/from-the-community-shared-governance/. 2023
• Student Activism, not Endowment Returns, Led to Recent Affordability Initiatives MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2022/02/02/from-the-community-student-activism-not-endowment-returns-led-to-recent-affordability-initiatives/. 2022
• A Primer on the Stanford Budget or: How I Learned to Stop Worrying and Love the Endowment MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2022/04/13/from-the-community-a-primer-on-the-stanford-budget/. 2022
• Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation. Cell chemical biology MacKenzie, T. M., Abderemane-Ali, F., Garrison, C. E., Minor, D. L., Bois, J. D. 2021

  Abstract

  Voltage-gated sodium channels (NaVs) are targets for a number of acute poisons. Many of these agents act as allosteric modulators of channel activity and serve as powerful chemical tools for understanding channel function. Herein, we detail studies with batrachotoxin (BTX), a potent steroidal amine, and three ester derivatives prepared through de novo synthesis against recombinant NaV subtypes (rNaV1.4 and hNaV1.5). Two of these compounds, BTX-B and BTX-cHx, are functionally equivalent to BTX, hyperpolarizing channel activation and blocking both fast and slow inactivation. BTX-yne-a C20-n-heptynoate ester-is a conspicuous outlier, eliminating fast but not slow inactivation. This property differentiates BTX-yne among other NaV modulators as a unique reagent that separates inactivation processes. These findings are supported by functional studies with bacterial NaVs (BacNaVs) that lack a fast inactivation gate. The availability of BTX-yne should advance future efforts aimed at understanding NaV gating mechanisms and designing allosteric regulators of NaV activity.

  View details for DOI 10.1016/j.chembiol.2021.12.003

  View details for PubMedID 34963066