Zachary Pincus, Ph.D.
My fundamental goal is to understand inter-individual variability in living systems: what are the origins of biological individuality? How is variance controlled, limited, and adaptively exploited?
In particular, my lab uses variability in Caenorhabditis elegans health and lifespan as a metazoan model of noise control, homeostatic robustness, and biological individuality. These processes have attracted considerable attention in bacteria, yeast, and single mammalian cells; however, there has been less investigation of the origins and implications of variability in multicellular organisms – a topic important for understanding how and why complex phenomena, such as age-related disease, manifest differently and at different times in individual humans.
Though famously invariant in its development, even genetically identical populations of C. elegans show a great degree of variability in later-life health, stress resistance, and longevity, as do higher animals. (Indeed, variation in human lifespan is under a surprisingly low degree of genetic control.) It is often presumed that lifespan variability, especially in controlled environments, is due to stochastic differences in damage accumulation over time; however, it is also possible that individual, epigenetic states of robustness exist, may be developmentally determined, and/or may be adaptive in the face of changing environments. My lab’s research draws on expertise in both bioinformatics and bench biology to rigorously investigate the origins of variability in individual health across entire populations.
Overall, these quantitative studies of inter-individual variability are a powerful technique for dissecting the operation of unperturbed biological systems, instead of relying on mutations and other interventions that may place a system in a non-physiological state. In this respect, this work is complementary to the common thread of systems biology, which seeks to understand the whole in terms of interactions and emergent properties of its parts. In contrast, these techniques are designed to understand the interactions of the parts by careful study of the whole.
- Zhang WB, Sinha DB, Pittman WE, Hvatum E, Stroustrup N & Pincus Z. Extended Twilight among Isogenic C. elegans Causes a Disproportionate Scaling between Lifespan and Health Cell Systems 3 (2016).
- Kinser HE, Pincus Z. High-throughput screening in the C. elegans nervous system. Mol Cell Neurosci. 2016 Jun 3.
- Pincus Z, Mazer TC, Slack FJ. Autofluorescence as a measure of senescence in C. elegans: look to red, not blue or green. Aging (Albany NY). 2016 May;8(5):889-98.
- Pincus Z. Ageing: A stretch in time. Nature. 2016 Feb 4;530(7588):37-8.
- Zhang WB, Pincus Z. Predicting all-cause mortality from basic physiology in the Framingham Heart Study. Aging Cell. 2016 Feb;15(1):39-48.
- Martínez LE, Hardcastle JM, Wang J, Pincus Z, Tsang J, Hoover TR, Bansil R, Salama NR. Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments. Mol Microbiol. 2016 Jan;99(1):88-110.
- Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, Svoronos A, Braddock DT, Glazer PM, Engelman DM, Saltzman WM, Slack FJ. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature. 2015 Feb 5;518(7537):107-10.
- Sycuro LK, Rule CS, Petersen TW, Wyckoff TJ, Sessler T, Nagarkar DB, Khalid F, Pincus Z, Biboy J, Vollmer W, Salama NR. Flow cytometry-based enrichment for cell shape mutants identifies multiple genes that influence Helicobacter pylori morphology.Mol Microbiol. 2013 Nov;90(4):869-83.
- Coburn C, Allman E, Mahanti P, Benedetto A, Cabreiro F, Pincus Z, Araiz C, Fischer G, Matthijssens F, Davidson A, Edwards S, Mandel A, Taylor A, Slack F, Braeckman B, Schroeder F, Nehrke K, Gems D. Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave that Promotes Organismal Death in C. elegans. PLoS Biol 11(7), e1001613. PMC3720247.
- Tevy MF, Giebultowicz J, Pincus Z, Mazzoccoli G & Vinciguerra M. 2013. Aging signaling pathways and circadian clock-dependent metabolic derangements. Trends Endocrin Metab 24(5) p. 229–237. PMID 23299029.
- Sycuro LK, Wyckoff TJ, Biboy J, Born P, Pincus Z, Vollmer W & Salama NR. 2012. Multiple Peptidoglycan Modification Networks Modulate Helicobacter pylori’s Cell Shape, Motility, and Colonization Potential. PLoS Pathog 8, e1002603. PMC3310797.
- Pincus Z, Smith-Vikos T, Slack FJ. 2011. MicroRNA Predictors of Longevity in Caenorhabditis elegans. PLoS Genet 7(9) e1002306. PMC3183074.
- Zhou KI, Pincus Z, Slack FJ. 2011. Longevity and stress in Caenorhabditis elegans. Aging 3(8) p. 733–753. PMC3184976.
- Dye NA, Pincus Z, Fisher IC, Shapiro L, Theriot JA. 2011. Mutations to the nucleotide binding pocket of MreB can alter cell curvature and polar morphology in Caulobacter. Mol Micro 81(2) p. 386–394. PMC3137890.
- de Lencastre A, Pincus Z, Zhou K, Kato M, Lee SS, Slack FJ. 2010. MicroRNAs Both Promote and Antagonize Longevity in C. elegans. Curr Biol 20(24) p. 2159–68. PMC3023310.
- Sycuro LK, Pincus Z, Gutierrez KD, Biboy J, Stern CA, Vollmer W, Salama NR. 2010. Peptidoglycan crosslinking relaxation promotes Helicobacter pylori’s helical shape and stomach colonization. Cell 141(5) p. 822–33. PMC2920535.
- Pincus Z, Slack FJ. 2010. Developmental biomarkers of aging in Caenorhabditis elegans. Dev Dyn 239(5) p. 1306–1314. PMC3073312.
- Kato M, de Lencastre A, Pincus Z, Slack FJ. 2009. Dynamic expression of small non-coding RNAs, including novel microRNAs and piRNAs/21U-RNAs, during Caenorhabditis elegans development. Genome Biol 10(5) p. R54. PMC2718520.
- Keren K*, Pincus Z*, Allen GM, Barnhart EL, Marriott G, Mogilner A, Theriot JA. 2008. Mechanism of shape determination in motile cells. Nature 453(7194) p. 475–80. PMC2877812.
For a complete list of Dr. Pincus's publications, click here
- Stanford University; B.S. 06/02 Biology
- Stanford University; Ph.D. 06/07 Biomedical Informatics
- Yale University; Postdoctoral 2007–2013 Molecular, Cellular, and Developmental Biology
Honors and Awards
- 2000 Barry M. Goldwater Scholarship (Barry M. Goldwater Scholarship and Excellence in Education Foundation)
- 2002 Firestone Medal for Excellence in Undergraduate Research (Stanford University)
- 2004 National Defense Science and Engineering Graduate Fellowship (American Society for Engineering Education / Department of Defense)
- 2004 NSF Graduate Research Fellowship (National Science Foundation; gratefully declined)
- 2006 Biosciences Graduate Education Award for Excellence in Teaching (Stanford University School of Medicine)
- 2006 President’s Award for Excellence (International Society for Analytic Cytology)
- 2007 Harold M. Weintraub Graduate Student Award (Fred Hutchinson Cancer Research Center)
- 2008 Jane Coffin Childs Postdoctoral Fellowship (Jane Coffin Childs Memorial Fund for Medical Research)
- 2012 Ellison/AFAR Postdoctoral Research in Aging Fellowship (Ellison Medical Foundation / American Federation for Aging Research; gratefully declined)
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