PhD Candidate Wins Prestigious Barbour Scholarship

May 4, 2023

Medicinal chemistry PhD candidate Jinghan Liu has earned a 2023 Barbour Scholarship. The award is among the oldest and most prestigious granted by the University of Michigan, offering funding to female students from Asia and the Middle East since 1917.

The Barbour Scholarship celebrates women of the highest academic and professional caliber and covers full tuition and required fees and a stipend for one academic year.

“I am in the final year of my PhD program,” says Jinghan. “This scholarship recognizes my research achievements and increases my confidence in my knowledge, my skills, and my ability to pursue my career.”

Jinghan Liu studies the structure and function of human bile acid biosynthetic and xenobiotic cytochrome P450 enzymes. She uses X-ray crystallography and different protein assays to understand P450 interactions with potential drugs, laying the groundwork for drug design for major human diseases and drug metabolism and toxicity predictions in neonates. Jinghan’s advisor is Emily Scott, PhD, F.F. Blicke Collegiate Professor of Medicinal Chemistry.

While some cytochrome P450 (CYP) enzymes clear drugs, others are good targets for drug inhibition in various diseases. However, the absence of structural and functional information for three human membrane proteins currently impedes these advances. 

“Inhibition of bile acid-generating CYP8B1 and CYP27A1 are two validated but unrealized approaches to treating nonalcoholic fatty liver disease and type 2 diabetes or breast cancer, respectively,” explains Jinghan. “A third P450, CYP3A7, is important in fetal development and drug clearance in premature infants. The structure/function strategy employed herein is to define atomic-level interactions between these three human P450 enzymes and relevant substrates and inhibitors. Such information is particularly hard to obtain because these proteins are normally found embedded in membranes and are less stable outside of the membrane environment.  The hard-won new information correlating structural and functional aspects will advance the development of CYP8B1 and CYP27A1 selective inhibitors, which will be helpful in the design of new therapeutic methods for these human diseases. The corresponding information for CYP3A7 will help predict variable drug clearance and make safer drug dosing guidelines for newborns.”

“Jinghan’s X-ray structure of cytochrome P450 8B1 is a critical piece of new information that is likely to enable new, real, achievable treatments for type 2 diabetes and an obesity-related disease,” says Dr. Scott. “Where absolutely no structural information was previously available for this bile-acid generating enzyme, Jinghan’s initial structure provides a template for the size, shape, and chemical features needed to design drugs for both diseases.”

“Overall, Jinghan is absolutely the kind of student that makes a mentor look good,” adds Dr. Scott. “Though she’s much too humble to say so herself, she’s one of those exceptional students who make sustainable contributions to our field and should be held up as examples to others, which is one of the motivating factors behind nominating her for the award.”

After graduation, Jinghan plans on working in the U.S. pharmaceutical industry for a couple of years. Afterward, she will return to China to work in an industry research and development position.

“I will use my knowledge and work experiences to support the long-term development of the pharmaceutical industry in China,” says Jinghan. “I plan on conducting more focused research on specific issues faced in China or medical research geared towards our population’s genetics which are missed in current clinical trials.”

 

 

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