# Michael C. Reed

- Professor of Mathematics

**External address:**237 Physics Bldg., Duke University, Box 90320, Durham, NC 27708

**Internal office address:**Box 90320, Duke University 90320, Durham, NC 27708-0320

**Phone:**(919) 660-2808

Professor Reed is engaged in a large number of research projects that involve the application of mathematics to questions in physiology and medicine. He also works on questions in analysis that are stimulated by biological questions. For recent work on cell metabolism and public health, go to sites@duke.edu/metabolism.

Since 2003, Professor Reed has worked with Professor Fred Nijhout (Duke Biology) to use mathematical methods to understand regulatory mechanisms in cell metabolism. Most of the questions studied are directly related to public health questions. A primary topic of interest has been liver cell metabolism where Reed and Nijhout have created mathematical models for the methionine cycle, the folate cycle, and glutathione metabolism. The goal is to understand the system behavior of these parts of cell metabolism. The models have enabled them to answer biological questions in the literature and to give insight into a variety of disease processes and syndromes including: neural tube defects, Down’s syndrome, autism, vitamin B6 deficiency, acetaminophen toxicity, and arsenic poisoning.

A second major topic has been the investigation of dopamine and serotonin metabolism in the brain; this is collaborative work with Professor Nijhiout and with Janet Best, a mathematician at The Ohio State University. The biochemistry of these neurotransmitters affects the electrophysiology of the brain and the electrophysiology affects the biochemistry. Both affect gene expression, the endocrine system, and behavior. In this complicated situation, especially because of the difficulty of experimentation, mathematical models are an essential investigative tool that can shed like on questions that are difficult to get at experimentally or clinically. The models have shed new light on the mode of action of selective serotonin reuptake inhibitors (used for depression), the interactions between the serotonin and dopamine systems in Parkinson’s disease and levodopa therapy, and the interactions between histamine and serotonin.

Recent work on homeostatic mechanisms in cell biochemistry in health and disease have shown how difficult the task of precision medicine is. A gene polymorphism may make a protein such as an enzyme less effective but often the system compensates through a variety of homeostatic mechanisms. So even though an individual's genotype is different, his or her phenotype may not be different. The individuals with common polymorphisms tend tend to live on homeostatic plateaus and only those individuals near the edges of the plateau are at risk for disease processes. Interventions should try to enlarge the homeostatic plateau around the individual's genotype.

Other areas in which Reed uses mathematical models to understand physiological questions include: axonal transport, the logical structure of the auditory brainstem, hyperacuity in the auditory system, models of pituitary cells that make luteinizing hormone and follicle stimulating hormone, models of maternal-fetal competition, models of the owl’s optic tectum, and models of insect metabolism.

For general discussions of the connections between mathematics and biology, see his articles: ``Why is Mathematical Biology so Hard?,'' 2004, Notices of the AMS, 51, pp. 338-342, and ``Mathematical Biology is Good for Mathematics,'' 2015, Notices of the AMS, 62, pp., 1172-1176.

Often, problems in biology give rise to new questions in pure mathematics. Examples of work with collaborators on such questions follow:

Laurent, T, Rider, B., and M. Reed (2006) Parabolic Behavior of a Hyberbolic Delay Equation, SIAM J. Analysis, 38, 1-15.

Mitchell, C., and M. Reed (2007) Neural Timing in Highly Convergent Systems, SIAM J. Appl. Math. 68, 720-737.

Anderson,D., Mattingly, J., Nijhout, F., and M. Reed (2007) Propagation of Fluctuations in Biochemical Systems, I: Linear SSC Networks, Bull. Math. Biol. 69, 1791-1813.

McKinley S, Popovic L, and M. Reed M. (2011) A Stochastic compartmental model for fast axonal transport, SIAM J. Appl. Math. 71, 1531-1556.

Lawley, S. Reed, M., Mattingly, S. (2014), Sensitivity to switching rates in stochastically switched ODEs,'' Comm. Math. Sci. 12, 1343-1352.

Lawley, S., Mattingly, J, Reed, M. (2015), Stochastic switching in infinite dimensions with applications to parabolic PDE, SIAM J. Math. Anal. 47, 3035-3063.

Lawley, SD, Cinderella, M, Hall, MN, Gamble, MV, Nijhout, HF, and Reed, MC. "Mathematical model insights into arsenic detoxification." *Theoretical biology & medical modelling* 8 (2011): 31--.
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Best, J, Nijhout, HF, and Reed, M. "Serotonin synthesis, release and reuptake in terminals: a mathematical model. (Published online)" *Theor Biol Med Model* 7 (August 19, 2010): 34-.
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Reed, MC, Lieb, A, and Nijhout, HF. "The biological significance of substrate inhibition: a mechanism with diverse functions." *Bioessays* 32.5 (May 2010): 422-429. (Review)
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Best, J, Reed, M, and Nijhout, HF. "Models of dopaminergic and serotonergic signaling." *Pharmacopsychiatry* 43 Suppl 1 (May 2010): S61-S66.
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Rios-Avila, L, Nijhout, HF, Reed, MC, Sitren, HS, and Gregory, JF. "Mathematical model gives insights into vitamin B6 and kynurenine metabolism." *FASEB JOURNAL* 24 (April 2010).

Reed, M, Lieb, A, and Nijhout, HF. "Biological Signiﬁcance of Substrate Inhibition." *BioEssays* 32 (2010): 422-429. (Academic Article)

Howell, AS, Savage, NS, Johnson, SA, Bose, I, Wagner, AW, Zyla, TR, Nijhout, HF, Reed, MC, Goryachev, AB, and Lew, DJ. "Singularity in polarization: rewiring yeast cells to make two buds." *Cell* 139.4 (November 13, 2009): 731-743.
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Thomas, DC, Conti, DV, Baurley, J, Nijhout, F, Reed, M, and Ulrich, CM. "Use of pathway information in molecular epidemiology." *Human genomics* 4.1 (October 2009): 21-42. (Review)
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Best, JA, Nijhout, HF, and Reed, MC. "Homeostatic mechanisms in dopamine synthesis and release: a mathematical model. (Published online)" *Theor Biol Med Model* 6 (September 10, 2009): 21-.
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Nijhout, HF, Gregory, JF, Fitzpatrick, C, Cho, E, Lamers, KY, Ulrich, CM, and Reed, MC. "A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism." *J Nutr* 139.4 (April 2009): 784-791.
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