Grad PhD Students
Research
Researchers have discovered that the Pyruvate kinase M2 (PKM2) enzyme plays a key role in glucose metabolism and energy expenditure. Building on that, JABSOM graduate student Katie Lee discovered the PKM2 protein is essential to heart health.
"People have explored PKM2 in the context of disease," Lee said. "The disease has already happened, and they're looking at what can be done with PKM2 to solve it. We wanted to see what PKM2 actually does in healthy hearts, and we discovered that your heart can't really be healthy without PKM2."
Lee's research will be published in Physiological Reports.
"The heart needs a lot of energy to contract and to move blood around your body, so it gets that energy by using a lot of sugars, mostly fats. and amino acids, for example," Lee explained. "We wanted to see if PKM2 made processing glucose more efficient and if it helps maintain energy when resources are limited, like oxygen."
Researchers used mice that didn't have PKM2 and found a severe depletion of Adenosine triphosphate (ATP), the energy source for use and storage at the cellular level. Lee found that to be especially true in murine heart cells in low oxygen conditions.
"That was the energy side of the research," Lee said. "What we didn't really expect to find is that there's this increase in other pathways that also use glucose, that normally are only turned on when you have stress signals in the cell. The stress we found is called oxidative stress that's turned on by harmful molecules called reactive oxygen species."
Lee discovered that instead of glucose being used for energy, it was used to help these pathways regulate the oxidative stress in hearts without PKM2.
"We found that this oxidative stress might be coming from the mitochondria, which makes the most ATP in the heart. So, instead of making energy, they were actually dysfunctional. They were less efficient in making energy. They were producing these reactive oxygen species in hearts without PKM2, so we ultimately found that PKM2 maintains energy and limits oxidative stress."
Lee is very excited that this research will be shared in the pages of Physiological Reports.
"This has been a paper that we've been waiting for years to be published, and it's been a journey to get all the right pieces together," Lee said. "If anyone's interested in reading it, they'll find years worth of data. I'm happy to push it out and move on to the next part!"
As an undergraduate student majoring in biochemistry at UH Mānoa, Lee got involved with JABSOM when she joined Dr. Peter Hoffman's lab to study melanoma. She continued with the INBRE program, and when she graduated, Lee was accepted to the Cell and Molecular Biology program, joining Dr. Ralph Shohet's laboratory to study cardiovascular disease. 