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The making of a scientist

| ShariLynn Lau '08, '11

Nicholas Warren has a personal history that inspired his choice to major in the sciences —specifically, in sciences related to cancer research.

"Both of my maternal grandparents died of pancreatic cancer," Warren said. "My grandmother's death was more painful for me personally because I had a close relationship with her, and she passed away while I was in high school. We didn't know what was wrong with her until five days before she died. I hope to prevent other families from going through that ordeal through work in cancer research."

Warren, a 2013 UW-Eau Claire biochemistry/molecular biology graduate, is continuing his education this fall as a Ph.D. student in cancer biology in Dartmouth College's Program in Experimental and Molecular Medicine.

Warren said one of the major reasons he chose to get his bachelor of science degree at UW-Eau Claire was because of its numerous opportunities for undergraduate research. Beginning his freshman year he researched methanobactin in the university's Materials Science Center.

"Methanobactin is a biomolecule used by methane-eating bacteria to absorb copper from the environment," Warren said. "Copper is important for this bacteria because it is used in the enzyme that converts methane (natural gas) into methanol. I developed a method to find how many ions methanobactin was able to bind to and reduce to a usable form. The long-term goal of this research is to be able to synthetically convert methane into methanol to be used as a replacement for gasoline. Methanol is greener, more renewable and potentially more plentiful than gasoline, and we wouldn't need to change our existing infrastructure to utilize it."

Warren's research on methanobactin was successful enough to be presented at UW-Eau Claire's 2010 Celebration of Excellence in Research and Creative Activity event, the 2012 chemistry department student seminars, the 2012 Provost's Honors Symposium and the 2012 National Conference of Undergraduate Research held at Weber State University in Ogden, Utah.

The methanobactin research project was done in collaboration with Marc McEllistrem, co-director of the Materials Science Center and associate professor of chemistry at UW-Eau Claire, who said Warren is someone who is drawn to new ideas and ways of thinking and is always looking for ways to express himself.

"Nick's self-confidence to approach me about doing research was also manifest in the lab as he rarely let setbacks deter him," McEllistrem said. "He was someone who liked a new challenge to tackle, and there are always many challenges in research.

"One of the common misconceptions students have as they arrive on our campus is that science is about 'knowing,' whereas science professionals are more driven by what is unknown. Over his time here, Nick grew increasingly comfortable saying, 'I don't know,' which I regard as an important step in his professional development."

According to Warren, the success of his methanobactin research also was a crucial factor in his gaining acceptance to an internship at Mayo Clinic in Rochester, Minn., where he studied muscle synthesis in diabetic mice and observed human studies on diabetes and exercise.

Warren said the project at Mayo Clinic looked at how diabetes affects muscle degradation. He took muscle samples from diabetic mice that were given different treatments with hormones, such as insulin and glucagon, or drugs and determined how much muscle degradation was present in each mouse.

"Muscles and cells in general will degrade themselves if they are starving and need energy," Warren said. "Insulin and glucagon are major signals to cells to take in nutrients, and we found that in general insulin decreases degradation and glucagon increases degradation, but more tests need to be done to confirm the findings. This research has implications for diabetics and elderly people who have lower levels of insulin secretion. Muscle mass is important for maintaining normal levels of blood sugar and greatly improves quality of life."

Warren's research on muscle synthesis on diabetic mice was presented at the 2012 Summer Undergraduate Research Symposium at Mayo Clinic and the 2012 biology department seminar series at UW-Eau Claire.

Associate professor of chemistry, Sanchita Hati and Nicholas WarrenWarren's second research project at UW-Eau Claire is ongoing and looks at the movement of proteins through computational chemistry, which is all done with computer programs. He explained that proteins vibrate and have larger-scale movements, which are vital to their function. He said he looked at the aminoacyl-tRNA synthetases (AARSs) since there are 20 of them divided into six subclasses and their protein structures are mostly known.

"AARSs charge tRNA molecules with an amino acid so it can be incorporated into a newly synthesized protein," Warren said. "We found that enzymes with similar structures showed similar movement patterns, and, therefore, the AARSs could be classified based on their movement patterns. We also found that seryl-tRNA synthetases' movement patterns did not quite fit with the traditional classification scheme and provided an argument to reclassify it with a different group of AARSs."

Warren said the purpose of the project is to demonstrate a new method of showing how enzymes carry out their reactions.

"This will help with basic research of understanding enzymes and, very far down the road, help make new targets for drugs," he said.

Nicholas Warren The AARS project, done in collaboration with Sanchita Hati, associate professor of chemistry at UW-Eau Claire, was presented at the 2013 CERCA event and also will be a first-author paper, which has been submitted to the scientific journal Proteins: Structure, Function, and Bioinformatics.

Hati worked closely with Warren as his research adviser and chemistry instructor.

"Nick was a very bright, hardworking and dedicated student," Hati said. "He was among the top three students in all three courses I taught. I was always very impressed with his analytical and problem-solving skills. He has an excellent level of maturity beyond many students in his age group."

Hati also commented on Warren's professionalism saying, "Nick was one of the very capable students with whom I have worked over the past seven years. I have been very impressed with his quest for learning new things and passion for science. I am sure that his good academic background, ability to think independently and strong motivation will enable him to succeed in his graduate school career."

Warren said he had many rewarding classes, including courses through the University Honors Program, and research experiences as an undergraduate at UW- Eau Claire.

"The Honors Program is full of very intellectually stimulating and exciting classes and hands-on learning opportunities," Warren said. "I formed strong relationships with my research advisers and feel the projects I worked on have been a great asset in helping me become a scientist. There really isn't any way to become a good researcher without actually doing it and making mistakes and then learning from those mistakes. A lot of research is just problem solving and coming up with new ways to answer your question."

Warren said he appreciated the freedom he experienced through the hands-off approach of his advisers, but he knew they were there to guide him in the right direction if he ever needed assistance.

"The great opportunities for research at UW- Eau Claire gave me a relatively safe environment to hone my researching skills and ask the important questions," he said.

Warren's participation in multiple research projects allowed him to graduate with chemistry department honors and university honors. He also played the cymbals for four years in the Blugold Marching Band.

"Detecting killer cancers, such as pancreatic cancer, earlier and having better treatments will remove much suffering from this world." —Nicholas Warren

In the next chapter of his continuing education, Warren said he is most looking forward to collaborative cancer research with his advisers at Dartmouth College.

"The advisers I'm most excited about working with are Drs. Alan Eastman and Todd Miller, assistant professors of pharmacology and toxicology," Warren said. "Dr. Eastman's project involves studying ways to better target cancer cells and leave healthy cells alone. The premise of this project is that healthy cells often have more than one pathway that perform a similar function, but only one pathway is needed for the cell to function. Cancer cells often have certain pathways shut down, so by shutting down the other redundant pathways we can kill the cancer cells while leaving the healthy cells alive."

One of the projects Warren will work on with Miller is closely related to the situation his grandmother faced during her battle with cancer, Warren said.

"When my grandmother became sick, her condition wasn't stable enough to perform a biopsy, so I am really interested in Dr. Miller's work on better detection methods," Warren said. "He is working on a new method to sequence DNA in blood samples to help detect and diagnose cancer without invasive biopsies. This would greatly improve the ability to detect pancreatic cancer and brain tumors since those organs are generally hard to access."

McEllistrem said he believes Warren has many of the attributes and skills that will help him in his graduate school career.

"Completing a doctorate in science requires that the researcher develop a sense of ownership for the project, but it also requires a sense of what to do when there is little guidance," McEllistrem said. "Often we start work by building on the published research of others, but if the forefront of knowledge is to be extended, the researcher has to be comfortable with ambiguity and a willingness to try a variety of things. Nick possesses this ability, and perhaps his most important attribute is a desire to forge ahead even though the path is unclear. For these reasons I would expect Nick to do well in graduate school."

Warren said his ultimate goal is to get a job researching in a clinical setting, such as Mayo Clinic, to develop new treatments and detection methods to help improve the quality of life for people with cancer.

"The current cancer treatments often have crippling side effects," Warren said. "We can extend the life of patients by about five years, but that is a very painful five years for them. Some patients are able to beat cancer but will have lasting effects from radiation or chemotherapy. Detecting killer cancers, such as pancreatic cancer, earlier and having better treatments will remove much suffering from this world."

Photos by Bill Hoepner

Image one: Sanchita Hati, associate professor of chemistry at UW-Eau Claire, worked closely with Nicholas Warren as his research adviser and chemistry instructor.

Image two: Nicholas Warren describes his research project during UW-Eau Claire's 2013 Celebration of Excellence in Research and Creative Activity event.