A Professor’s research on how pharmaceuticals interact with our biomolecules may lead to less toxic treatments.

Story by Gabrielle Ciraco

Pharmaceuticals are often necessary in the fight against cancer. But targeting cancer cells has a harsh impact on other cells in the human body, often leading to side effects such as infertility, hair loss and digestive problems. 

Ruel McKnight, professor of chemistry and biochemistry at Geneseo, has spent more than 15 years trying to understand why there are such severe side effects by examining how components of anti-cancer drugs interact with our body’s molecules. His research may help pharmaceutical companies develop effective yet less toxic medicines in the future. 

“Everyone has seen those pharmaceutical commercials where a narrator is speaking about a drug and how it can help you,” says McKnight, “but then he speaks really fast listing all of the different side effects.” 

According to McKnight, the fundamental reason for these side effects is that the drug targets not only problematic cells, but normal ones. Drugs with fewer side effects are considered more targeted or selective because they almost exclusively target the desired cells or DNA. Although the anti-cancer drugs we have on the market have improved over time, most are not as targeted as we would like them to be, says McKnight. 

“Cancer cells are just normal cells that have been reprogrammed to divide uncontrollably, so many anti-cancer drugs are designed to hinder rapidly dividing cells. Unfortunately, any cells that divide rapidly, such as reproductive cells, will be affected,” says McKnight. “Those also include cells involved with hair growth and digestion, for example.” 

McKnight and his research students use several state-of-the-art biophysical instruments to study the interaction of drugs to DNA. “One of my favorites is an isothermal titration calorimeter (ITC),” says McKnight. “Although this instrument is used in the pharmaceutical industry, especially to find lead compounds/ drugs, not many academic labs use it to study drug-DNA interactions.” 

Such instruments can be costly and the data difficult to interpret, says McKnight, but using these instruments to study drug-DNA interactions yields unique information, such as the energy that is transferred during a biological interaction. One of the approaches he uses (a topoisomerase DNA unwinding assay) is somewhat unique to his lab because of modifications he made and the way he uses it. This technique has led to research collaborations with the University at Buffalo, the University of the West Indies (his alma mater), and a team from India, which led to several publications. 

McKnight says researchers are often shocked to hear that the work in his lab is conducted by undergraduates. Each semester, he works with three to five students, who get the chance to fully use and understand the instruments. Biochemistry major and math minor Joseph “Joe” Kanlong ’19 developed a technique inspired by relevant literature and three semesters of study under McKnight. 

“We had some drugs that were not very water-soluble and couldn’t successfully be studied using ITC,” says McKnight. “Joe was able to design a procedure that we could use to study his compounds.” 

“I’m interested in continuing anti-cancer therapeutics research,” says Kanlong, who says research has helped give him “an ability to think independently and create a solution-focused mindset.” 

Some of McKnight’s students have presented their work at the American Chemical Society (ACS) and other national meetings. Kanlong presented his work at the American Society of Biochemistry and Molecular Biology (ASBMB) conference in Orlando last semester. McKnight aims to publish his findings before the end of the year and to attend conferences with other experts in the field in Europe.