# Michael C. Reed

- Professor of Mathematics
- Arts & Sciences Professor
- Bass Fellow

**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.

Duncan, TM, Reed, MC, and Nijhout, HF. "The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: A model." *Molecular Nutrition and Food Research* 57.4 (2013): 628-636.
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Best, J, Reed, MC, and Nijhout, HF. "Computational studies of the role of serotonin in the basal ganglia." *Frontiers in Integrative Neuroscience* MAY (2013).
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Ben-Shachar, R, Chen, Y, Luo, S, Hartman, C, Reed, M, and Nijhout, HF. "The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model. (Published online)" *Theor Biol Med Model* 9 (December 19, 2012): 55-.
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Luo, S, Reed, M, Mattingly, JC, and Koelle, K. "The impact of host immune status on the within-host and population dynamics of antigenic immune escape." *J R Soc Interface* 9.75 (October 7, 2012): 2603-2613.
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Obeid, R, Hartmuth, K, Herrmann, W, Gortner, L, Rohrer, TR, Geisel, J, Reed, MC, and Nijhout, HF. "Blood biomarkers of methylation in Down syndrome and metabolic simulations using a mathematical model." *Mol Nutr Food Res* 56.10 (October 2012): 1582-1589.
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Geenen, S, du Preez, FB, Reed, M, Nijhout, HF, Kenna, JG, Wilson, ID, Westerhoff, HV, and Snoep, JL. "A mathematical modelling approach to assessing the reliability of biomarkers of glutathione metabolism." *European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences* 46.4 (July 2012): 233-243.
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Luo, S, Reed, M, Mattingly, J, and Koelle, K. "population dynamics of antigenic immune escape The impact of host immune status on the within-host and." *J. Royal Soc. Interface* (doi: 10.1098/rsif.2012.0180) (2012). (Academic Article)

Mitchell, C, and Reed, MC. "Do Real Neurons Have Time Windows? (Submitted)." *Journal of Computational Neuroscience* (2012). (Academic Article)

Reed, MC, Nijhout, HF, and Best, JA. "Mathematical insights into the effects of levodopa. (Published online)" *Front Integr Neurosci* 6 (2012): 21-.
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Neuhouser, ML, Nijhout, HF, Gregory, JF, Reed, MC, James, SJ, Liu, A, Shane, B, and Ulrich, CM. "Mathematical modeling predicts the effect of folate deficiency and excess on cancer-related biomarkers." *Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology* 20.9 (September 2011): 1912-1917.
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