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Daniel Sem, Ph.D., wanted to put a heart in hard science —
something that wasn’t always easy when he worked in the profit-driven biotechnology industry.
Daniel Sem , Ph.D., assistant professor of chemistry and director of the Chemical Proteomics Facility at Marquette. He was the first to create a fluorescent probe that could measure the oxidation state inside living cells.
“Whenever I would talk about tuberculosis, that would always make the venture capitalists cringe… because there’s not enough money to be made,” says Sem, who was founder and vice president for biophysics at Triad Therapeutics in San Diego. “They told me, ‘Your motivation has to be in one place or the other. Are you trying to make money or are you trying to sort of save the world?’ And my thinking was, ‘Can’t we try to do both?’”
Now Sem, an assistant professor of chemistry, can focus on the underdogs: diseases that don’t get enough attention and the dangerous side effects of drugs and pollutants. His passion for applied research found a home in Marquette’s Jesuit, service-oriented mission.
Sem’s specialty is chemical proteomics, which is the study of how chemicals interact with proteins. You could have several thousand proteins in a cell, but only a few might interact with a certain chemical.
“I view it as a constant war that’s going on between us and our environment,” he says. “Chemicals can be drugs that are attacking certain proteins and having a desired effect, or they could be pollutants that are attacking and having an undesired effect. It’s sort of the yin and the yang of chemicals.”
At Marquette, Sem has state-of-the-art tools to study that war. He’s the founding director of the Chemical Proteomics Facility, which recently received $1.2 million of new equipment funded in part by the National Institutes of Health and the National Science Foundation. The big gun is a powerful 600 MHz nuclear magnetic resonance spectrometer, which allows researchers to study the structure of proteins and their interactions with chemicals. A second new instrument, a 400 MHz spectrometer, has a robotic arm that can analyze hundreds of samples overnight.
Sem’s recent work has included researching proteins in Mycobacterium tuberculosis that could be targets for new anti-TB drugs, studying estrogen receptors in zebrafish, and examining a troublesome enzyme that metabolizes nearly one-third of all drugs in humans.
To study a pollutant that is causing birth defects in aquatic wildlife, he designed a fluorescent molecule that binds to the estrogen receptor, which allows him to see what’s happening inside developing fish. The binding site for zebrafish is nearly identical to that of humans, so zebrafish could be used to screen for human breast cancer therapeutics or to learn how pollutants are affecting the human body. Next, he’ll use nuclear magnetic resonance instead of fluorescence.
“If we could turn this into an imaging probe, an MRI probe, then we could use it as a diagnostic for humans,” Sem says.
Sem also developed chemical probes that assess the environment inside a cell.
“It turns out that a lot of diseases — Alzheimer’s, arthritis, Parkinson’s — all show an imbalance in the oxidation state of a cell,” he says. “It’s a way of measuring that things are wrong inside the cell.”
Sem was the first to create a fluorescent probe that could measure the oxidation state inside living cells, filling a crucial gap in what scientists understand about cell biology. The probe can also be used to see how drugs are working.
Sem is also researching the enzyme CYP2D6, which metabolizes 30 percent of drugs in the liver. In effect, that enzyme destroys a drug’s effectiveness before it’s even had a chance to work.
“We want to better predict what kind of chemicals bind to these proteins,” Sem says. “Then there’s the basic research question of trying to understand how one protein with just one little pocket can bind to hundreds of molecules. If it’s like a lock and a key, how can one lock recognize several hundred keys? That’s the mystery we’re trying to solve.”
Life Cycle: From Birth to Death
- Unraveling the mysteries of proteins
- Protecting brittle bones
- Understanding the damaged brain
- The lungs: more than gas exchange
- The mind-body connection
- Preserving family peace
- Bringing clarity to delirium
- Protecting muscles on and off Earth
Improving the Human Condition
Studying Our World
Ethics & social justice
- Keeping business honest
- Of humans and cyborgs
- Journalism, ethics and the law
- Punishing corporate crime
- Dissecting financial fraud
- Scrutinizing elder law
Student Research
Interdisciplinary Research
Quick Facts About Marquette
| Identity: | Catholic, Jesuit, private |
| Established: | 1881 |
| Location: | Milwaukee, Wisconsin |
| Undergraduate: | 8,048 |
| Postgraduate: | 3,500 |
| Campus: | Urban, 80 acres |
| Athletics: | 11 NCAA Division I teams (Big East Conference) |
| Colors: | Blue and Gold |
