# Matthew Hirschey


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2023 -

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Founded [Heureka Labs](https://www.heurekalabs.co), building AI foundation models trained on multi-omic experimental data to help researchers find patterns in biological systems. Our desktop app, Heureka Bench, brings model querying, lab management, literature curation, and cloud compute into one place for organizing and analyzing scientific work.

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2021 -

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I am the inaugural Director of the Duke [Center for Computational Thinking](https://computationalthinking.duke.edu). The CCT is a University-wide initiative to make computational thinking part of every discipline. Programs, partnerships, and AI literacy work for students, faculty, and leadership across Duke.

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2011 -

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I joined the faculty of [Duke University](https://medicine.duke.edu) and started the [Hirschey Lab](https://www.hirscheylab.org), housed in the [Duke Molecular Physiology Institute](https://dmpi.duke.edu). The lab studies how cells integrate nutrient sensing and metabolism. I was promoted to tenured Associate Professor in 2019. I also hold a joint appointment at Duke-NUS in Singapore.

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2006 - 2011

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I did post-doctoral research with [Eric Verdin](https://en.wikipedia.org/wiki/Eric_Verdin) at the Gladstone Institutes at UCSF. I worked on mammalian sirtuins and the biology of aging.

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2001 - 2006

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My Ph.D. was in Chemistry & Biochemistry at UC Santa Barbara with [Alison Butler](https://labs.chem.ucsb.edu/butler/alison/). I combined inorganic semiconductor synthesis with microbiology, where I functionalized nanocrystals called quantum dots for new kinds of biological imaging.

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1997 - 2001

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B.S. in Biological Sciences at the University of Vermont, with research in mesoporous silica with [Chris Landry](https://www.uvm.edu/cas/chemistry/profile/christopher-c-landry) and glutathione metabolism with [Naomi Fukagawa](https://en.wikipedia.org/wiki/Naomi_Fukagawa).

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bio

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Matthew Hirschey is a tenured Associate Professor at Duke University in the Departments of Medicine (Endocrinology, Metabolism & Nutrition) and Pharmacology & Cancer Biology, and a faculty member of the Duke Molecular Physiology Institute. Since 2021 he has been the inaugural Director of the Duke Center for Computational Thinking. His lab studies how cells integrate nutrient sensing and metabolism, using data-driven approaches to surface new regulatory pathways relevant to diabetes, cardiovascular disease, cancer, and aging. His work has appeared in *Nature*, *Science*, *Cell Metabolism*, and *Molecular Cell*, and is supported by the NIH, DOD, and OpenAI. He lives with his wife and children in Durham, NC.

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    <div class="ctitle">featured talks</div>
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        <span class="cyear">2026</span>
        <span class="cvenue">BCG × QS: Workforce, AI, and the Future of Skills</span>
        <span class="cloc">Washington, D.C.</span>
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        <span class="cyear">2025</span>
        <span class="cvenue">OpenAI Discussion with Sarah Friar (moderator)</span>
        <span class="cloc">Duke University</span>
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        <span class="cyear">2025</span>
        <span class="cvenue">UseR! 2025 — Co-Organizer & Speaker</span>
        <span class="cloc">Duke University</span>
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        <span class="cyear">2025</span>
        <span class="cvenue">International Symposium for Organelle Medicine</span>
        <span class="cloc">Yonsei University, Korea</span>
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        <span class="cyear">2024</span>
        <span class="cvenue">Duke AI Summit</span>
        <span class="cloc">Duke University</span>
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        <span class="cyear">2023</span>
        <span class="cvenue">10th Helmholtz Diabetes Conference</span>
        <span class="cloc">Munich, Germany</span>
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        <span class="cyear">2022</span>
        <span class="cvenue">American Diabetes Association 82nd Annual Meeting</span>
        <span class="cloc">New Orleans, LA</span>
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        <span class="cyear">2019</span>
        <span class="cvenue">Keystone: Mitochondria in Aging & Age-Related Disease</span>
        <span class="cloc">Keystone, CO</span>
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teaching

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At Duke I teach across the medical school, graduate programs, and undergraduate curriculum, with a consistent throughline: using biological data to tell a story. As Director of the [Center for Computational Thinking](https://computationalthinking.duke.edu), I also build programs that put computational thinking into the hands of students across every discipline.

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- **CMB710 · TidyBiology** — An Introduction to Biological Data Science in R. A flagship course, taught yearly since 2019.
- **HSF · Human Structure & Function** — Medical student curriculum, metabolism/endocrinology modules.
- **MCB818 · Molecular Mechanisms of Oncogenesis** — Graduate cancer biology, 2022 – 2025.
- **MCB820 · Cancer Research from Concept to Translation** — 2026.
- **PCB710 · Grant Writing** — 2017 – 2022.
- **UNIV103 · Let’s talk about: Digital You** — An undergraduate seminar on identity and attention online.

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writing

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Most of my writing shows up in academic journals, but I also have an occasional blog — [**Heureka Labs**](https://www.heurekalabs.org) — with essays on creativity, computational thinking, and experiments in how we think.

A few selected pieces:

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    <a href="https://www.heurekalabs.org/a-new-experiment/" class="wthumb"><img src="img/post-new-idea.jpg" alt="How do you come up with a new idea?" /></a>
    <a href="https://www.heurekalabs.org/a-new-experiment/" class="wtitle">How do you come up with a new idea?</a>
    <div class="wdesc">On the mechanics of ideation and why the interesting question isn’t
“what should I work on” but “how did you decide what to try.”</div>
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    <a href="https://www.heurekalabs.org/sell-the-sawdust/" class="wthumb"><img src="img/post-sawdust.jpg" alt="Sell the sawdust" /></a>
    <a href="https://www.heurekalabs.org/sell-the-sawdust/" class="wtitle">Sell the sawdust</a>
    <div class="wdesc">On the byproducts of research and the overlooked value hiding in the
scraps of what you’re already doing.</div>
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    <a href="https://www.heurekalabs.org/why-learn-to-program/" class="wthumb"><img src="img/post-program.jpg" alt="Why you need to learn to program" /></a>
    <a href="https://www.heurekalabs.org/why-learn-to-program/" class="wtitle">Why you need to learn to program</a>
    <div class="wdesc">The case for programming as a thinking tool, not a job skill — for
scientists, students, and pretty much everyone else.</div>
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    <div class="pico"><img src="img/ddh-logo.png" alt="Data-Driven Hypothesis" /></div>
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      <a href="https://www.datadrivenhypothesis.com"><b>Data-Driven Hypothesis</b></a> — A web tool that integrates DepMap, expression, and literature data to
suggest functions for understudied genes. Pairs with the pathway
co-essentiality work in the lab. Preprint on bioRxiv, 2026.
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selected publications

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A curated list. For the full record (nearly 100 papers, books, and chapters) see the [CV](Hirschey_CV.pdf).

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<span class="pub-title">Pathway Coessentiality Mapping Reveals Complex II is Required for de novo Purine Biosynthesis in Acute Myeloid Leukemia.</span> <span class="pub-authors">Stewart AE\*, Zachman DK\*, Castellano-Escuder P, et al.</span> <span class="pub-venue">Nature Metabolism (2025, in press)</span>

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<span class="pub-title">Interpretable multi-omics integration with UMAP embeddings and density-based clustering.</span> <span class="pub-authors">Castellano-Escuder P, Zachman DK, Han K, Hirschey MD.</span> <span class="pub-venue">Nature Communications (2025) 16:5771</span>

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<span class="pub-title">Cysteine S-acetylation is a post-translational modification involved in metabolic regulation.</span> <span class="pub-authors">Keenan EK, Bareja A, Lam Y, Grimsrud PA, Hirschey MD.</span> <span class="pub-venue">Nature Metabolic Health & Disease (2025) 3:43</span>

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<span class="pub-title">Statin therapy inhibits fatty acid synthase via dynamic protein modifications.</span> <span class="pub-authors">Trub AG, Wagner GR, Anderson KA, et al.</span> <span class="pub-venue">Nature Communications (2022) 13:2542</span>

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<span class="pub-title">The Growing Landscape of Protein Modifications.</span> <span class="pub-authors">Keenan EK, Zachman DK, Hirschey MD.</span> <span class="pub-venue">Molecular Cell (2021) 81(9):1868-1878</span>

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<span class="pub-title">Creating An Environment For A Distributed Scientific Workforce.</span> <span class="pub-authors">Hirschey MD.</span> <span class="pub-venue">Nature (2020) 582:184</span>

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<span class="pub-title">SIRT4 is a Lysine Deacylase That Controls Leucine Metabolism and Insulin Secretion.</span> <span class="pub-authors">Anderson KA, Huynh FK, Fisher-Wellman K, et al.</span> <span class="pub-venue">Cell Metabolism (2017) 25(4):838-855</span>

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<span class="pub-title">A Class of Reactive Acyl-CoA Species Reveals the Nonenzymatic Origins of Protein Acylation.</span> <span class="pub-authors">Wagner GR, Bhatt DP, O’Connell TM, et al.</span> <span class="pub-venue">Cell Metabolism (2017) 25(4):823-837</span>

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<span class="pub-title">Role of NAD⁺ and mitochondrial sirtuins in cardiac and renal diseases.</span> <span class="pub-authors">Hershberger KA, Martin AS, Hirschey MD.</span> <span class="pub-venue">Nature Reviews Nephrology (2017) 13(4):213-225</span>

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<span class="pub-title">Non-enzymatic protein acylation as a carbon stress regulated by sirtuin deacylases.</span> <span class="pub-authors">Wagner GR, Hirschey MD.</span> <span class="pub-venue">Molecular Cell (2014) 54(1):5-16</span>

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<span class="pub-title">Lysine Glutarylation Is a Protein Post-Translational Modification Regulated by SIRT5.</span> <span class="pub-authors">Tan M\*, Peng C\*, Anderson KA\*, et al.</span> <span class="pub-venue">Cell Metabolism (2014) 19(4):605-617</span>

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<span class="pub-title">Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor.</span> <span class="pub-authors">Shimazu T, Hirschey MD, Newman J, et al.</span> <span class="pub-venue">Science (2013) 339:211-214</span>

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<span class="pub-title">SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome.</span> <span class="pub-authors">Hirschey MD, Shimazu T, Jing E, et al.</span> <span class="pub-venue">Molecular Cell (2011) 44:177-190</span>

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<span class="pub-title">SIRT3 Deacetylates Mitochondrial HMG-CoA Synthase 2 and Regulates Ketone Body Production.</span> <span class="pub-authors">Shimazu T\*, Hirschey MD\*, Ha L, et al.</span> <span class="pub-venue">Cell Metabolism (2010) 12:654-661</span>

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<span class="pub-title">SIRT3 regulates mitochondrial fatty acid oxidation via reversible enzyme deacetylation.</span> <span class="pub-authors">Hirschey MD, Shimazu T, Goetzman E, et al.</span> <span class="pub-venue">Nature (2010) 464:121-125</span>

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misc

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- I make [art](https://foundation.app/matthewhirschey) when I want to create.
- Currently learning: how to teach computational thinking to people who have never written a line of code and don’t plan to.
- If you’re a prospective trainee: start with the [lab site](https://www.hirscheylab.org).
- Eagle Scout.

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