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Christal Sohl, Ph.D.

Christal Sohl, Ph.D., of San Diego State University, studies enzymes that may play a role in cancer.

Credit: National Cancer Institute / Christal Sohl, Ph.D.

It was in an undergraduate biochemistry course at the University of Oklahoma that Christal Sohl, Ph.D., first learned about enzyme kinetics—the study of the mechanisms by which enzymes transform a biological substrate into a product. Although she had been doing very well in the course, she did poorly on one exam.

“It frustrated me so much that something had conquered me,” she says. “So I went back to it and spent a lot of personal time learning about enzyme kinetics—and along the way, I fell in love with it.” With hard work and perseverance, Dr. Sohl ultimately passed the course with flying colors.  

Dr. Sohl started her research career as an undergraduate in the lab of George Richter-Addo, Ph.D., studying how environmental pollutants and carcinogens interact with models of heme to affect their function. Although she enjoyed this research, she became interested in exploring what happens when an enzyme itself is directly altered in some way.

So she went to graduate school in the lab of Fred Guengerich, Ph.D., at Vanderbilt University. Dr. Guengerich is a biochemist whose expertise is teasing out every single step of a potentially complicated enzymatic reaction. He was the mentor who “transformed my career,” said Dr. Sohl.

Toward the end of graduate school, she knew she wanted to pursue research in enzymology, but she also wanted to focus on a clinically relevant problem.

This goal brought her to the lab of Karen Anderson, Ph.D., at Yale University, where as a postdoc Dr. Sohl applied the techniques she had learned towards problems that are directly relevant to human disease. She worked on kinases—cellular signaling proteins that control, among other things, cell growth and division. Although several cancer drugs targeting kinases already exist, there are many more kinases that have not been targeted yet.

Becoming an Independent Investigator

Dr. Sohl is now an assistant professor in the Department of Chemistry and Biochemistry at San Diego State University (SDSU), and her research goal is to understand how a mutation leading to a change in enzyme structure affects the enzyme’s ability to do its job inside the cell, she explained.

She received a K99/R00 transition grant through NCI to study isocitrate dehydrogenase, an enzyme whose function is drastically changed by a single point mutation. The mutation, in some circumstances, can have tumor-suppressing effects, but it can also cause the enzyme to produce a cancer-promoting metabolite, called an onco-metabolite. So Dr. Sohl uses a variety of assays to understand how this enzyme functions in both its original and mutated conditions. She also studies polymerases, the enzymes that are involved in DNA replication. Mutations in polymerase enzymes can lead to faulty or inaccurate DNA replication, which can introduce mutations into the DNA strands and potentially lead to cancer.

The Importance of Mentoring

Dr. Sohl credits the K99/R00 grant with giving her the opportunity to cultivate strong mentoring relationships that helped advance her career at the critical transition from postdoctoral fellow to assistant professor.

“There aren’t a lot of formal opportunities for mentoring in postdocs, but the K99/R00 grant application gives you a reason to ask mentors to help you,” she said. “It made preparing job applications much faster. Seeking out mentors was something that was very hard to do as a postdoc, but the K99 strongly recommends that you do this, and it’s wonderful.”

The process of applying for the K99/R00 grant will help enormously when the time comes to apply for her first R01 grant. “It’s a very daunting prospect for the first grant application to be an R01,” she said. “It is nice to have a little confidence and know that you’ve done these things before. You kind of know how the game works and what the requirements are.”

Dr. Sohl is excited to be a brand-new assistant professor. Between teaching, doing research, mentoring students, serving on committees, and more, “You get to do a lot of different things as an assistant professor,” she said. “It’s pretty terrific. Having the opportunity to help SDSU students become inspired by research and science in general—it’s an honor to be able to do that,” she said.

“I’ve been really impressed by how generous people have been with their time in mentoring. I will certainly pay that forward when it’s time for me to serve as a mentor for people at earlier career stages than myself,” she said.

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