Northwestern Chemistry students, Rad Chrzanowski, Alejandro Medina, and Tiger Wang, were the recipients of this year’s Lambert Fellowship, the most prestigious undergraduate award awarded by Chemistry of Life Processes Institute. Recipients were selected based on their academic achievements and scientific interests. The two-year fellowship provides mentorship by CLP faculty members, postdoctoral and graduate students who share the same interests, skills development and support for laboratory research conducted in CLP faculty laboratories.

This year, all three awardees are fellows in the Silverman Lab, led by Richard Silverman, PhD, the developer of pregabalin, the chemical that became the blockbuster drug Lyrica®.

Targeting liver cancer

Alejandro Medina, a junior double-majoring in chemistry and biology, is working on synthesizing a drug-like molecule that inactivates an enzyme overexpressed in hepatocellular carcinoma (HCC) cells. HCC is one of the most common and aggressive types of liver cancer.

“Our molecules are designed to take advantage of the target enzyme’s natural catalytic mechanism to turn our drug into a reactive species that will covalently inactivate our target enzyme,” says Medina. “However, they’re not perfect. It is still relatively common that they get activated by the enzyme and then leave. This could potentially be toxic to our bodies.  The hope with making stronger and more potent molecules is that they’d be more likely to stay in the enzyme pocket and inactivate it instead of float off and produce unwanted side effects.”

Medina is interested in pursuing his PhD in chemistry after graduation with an eye towards a possible career in academia following the footsteps of his mom who teaches Anthropology at a Big 10 school.

“Part of the reason I tried for this fellowship was that I wasn’t sure I wanted a research career,” says Medina, “but I actually like going into work. I really enjoy it.”

Controlling epilepsy

Designing an enzyme-inhibiting molecule to better control epilepsy is the focus of junior Tiger Wang’s project in the Silverman lab.

“I’m primarily focused right now on synthesis chemistry, using organic chemistry to design molecules that inhibit gamma-aminotransferase (GABA-AT),” says Wang, a junior majoring in chemistry and biology. Compounds that inhibit this enzyme raise brain GABA levels. GABA is a chemical messenger that slows the brain’s function.

Wang says he will likely apply to graduate school after college to gain more experience doing research and publishing his work.

“My main goal is to build my scientific foundations and knowledge base. I want learn as much as I can,” says Wang. “The Lambert Fellowship has provided me with a precious opportunity to do some actual research and explore the areas that I’m interested in.”

Reducing the risk of neurodegenerative disease

Rad Chrzanowski, a junior double majoring in chemistry and biology, is building upon 20 years of research in the Silverman Lab to find small molecules that inhibit neuronal nitric oxide synthase or nNOS, an enzyme that produces nitric oxide.

“Nitric oxide is responsible for regulating blood pressure and also stimulating immune responses,” says Chrzanowski, “but in the brain, it has been associated with neurotoxicity and neurodegenerative diseases, such as Alzheimer’s. The goal of the project is to produce molecules that are able to mediate the activity of that enzyme and decrease the concentration of nitric oxide in the brain.”

Chrzanowski is weighing his options carefully after graduation: he is considering graduate school or applying for an MD/PhD program.

“To know that my research proposal was considered significant enough for CLP to fund was a game changer,” says Chrzanowski. “It gave me the confidence and motivation to continue on the path of research beyond my immediate project.”

The Lambert Fellowship was founded in 2010, and endowed in 2016, by CLP Executive Advisory Board Chairman and Vice President of Research Biology at Genentech, Andrew Chan, MD, PhD ’80, ’80 MS (Weinberg). The program is named in honor of Dr. Joseph B. Lambert, the Clare Hamilton Hall Professor of Chemistry.  Professor Lambert was Dr. Chan’s advisor in the late 1970’s at Northwestern and had a profound impact on Chan’s educational experience.

by Lisa La Vallee