Research Overview

Professor Millard (right) was named a Fellow of the American Association for the Advancement of Science in 2016.

The Millard research team has been working on projects involved in human health since 1991. We have ongoing projects in several different areas, including characterizing the mechanisms of anti-cancer drugs, investigating factors that mediate the effects of caffeine on performance, and developing forensic applications of DNA analysis. Below is more information about the current work in our lab. Above is the summer research team of Vanesa Silvestri ’12 (now at Johns Hopkins), Adam Spierer ’13 (now at Brown University), and Eddie Chuang ’14 (now at the University of Pennsylvania).

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Forensic Applications of DNA Analysis

HLA-A typing can be used to investigate the zygosity of twins.

The famous fictional detective Sherlock Holmes stated, “It has long been an axiom of mine that the little things are infinitely the most important.” We are interested in how DNA is used to solve crimes and other mysteries. For example, how can you tell for sure whether a pair of twins is identical or fraternal? We recently looked into this question by using PCR to type at the HLA-A gene, which has about 1939 different alleles. We have also used DNA typing on dogs and horses!

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Factors that Influence Caffeine’s Effects

We can easily measure lactate concentration from a single spot of blood.

Caffeine has a wide range of effects in the human body, including vasoconstriction, bronchodilation, and stimulation of fat breakdown. Despite its widespread use, caffeine affects individuals very differently. Some people drink coffee all day, even right before bed, while others get jittery after a single cup. Lots of people consume caffeine to try to improve athletic performance, but the data are mixed as to its benefits. One reason for these different outcomes could be genetic. We are genotyping human subjects, studying rates of caffeine clearance, and beginning studies on the effects of caffeine on lactate production in collegiate athletes.

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Mechanisms of Anti-Cancer Drugs

Many anti-cancer agents work by binding to DNA. We have characterized DNA sites targeted by interstrand cross-linking agents and probed structural abnormalities induced by cross-linking. We are currently most focused on diepoxybutane, the active form of the prodrug treosulfan, which is used to treat ovarian cancer. Related compounds of interest include nitrogen mustard, the first synthetic compound used in cancer chemotherapy, and epichlorohydrin, widely used in the synthetic polymer industry.

Characteristic comet shapes after treatment  of human leukemia cells with hydrogen peroxide.

One project currently underway investigates whether the DNA products formed by some anti-cancer drugs, such as cisplatin, may lead to mutagenesis. This might help explain why patients who receive cancer chemotherapy have higher rates of cancer many years after treatment.

Another ongoing project quantifies cross-linking by anti-cancer drugs in leukemia cells. Treatment with hydrogen peroxide leads to “comet” shapes of single cells after electrophoresis, but cross-links reduce the length of the comet tail.

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