Dr. Kshitiz, a professor in the Department of Biomedical Engineering and an investigator at the Yale Center of Cancer Systems Biology, along with collaborators Andre Levchenko at Johns Hopkins and Chi V. Dang at Yale and students have discovered a unique aspect of cancer cells. After years of studying these cells in low-oxygen environments, the researchers observed that while most cells are unable to live without adequate oxygen, select cancer cells are able to continue to grow because of one protein.
Wanting to gain a better understanding of why this was happening, the group looked deeper into the biological basis of this phenomenon and why these cancer cells were able to “cheat” the conditions as they were.
“It’s a beautiful, very elegant system. Oxygen sensing is central to any complex organism functioning. When cancers start developing, until they are able to vascularize themselves, they have a lack of oxygen, which is called hypoxia,” Kshitiz explained in an interview with The Daily Campus.
Research published by the group details the role of a protein called HIF-1α in hypoxia as it relates to cancer. Although HIF-1α is normally responsible for suppressing cell growth, this is the opposite of what the group of researchers observed with the cancer cells.
“This is a conundrum because we know that cancers keep growing in the body despite a lack of oxygen,” Kshitiz said.
Using various techniques, the researchers discovered that a group of cells were defying expectations and the reason these cells were able to do so.
“There was a small number of cells that were cheating, and were basically able to oscillate the levels of HIF-1α … thereby continuing to divide and cheat the rest of the cancer cells,” Kshitiz explained.
Members of the Kshitiz Lab come from diverse backgrounds and intertwine techniques from molecular biology, computer science, biophysics and more fields to come up with answers to problems ranging from these “cheater” cancer cells to cardiac maturation. This interdisciplinary approach is characteristic of systems biology and the research group which, according to Kshitiz, focuses on taking a holistic approach to a given biological problem.
“There are recurring themes in biology…and we try to find the same cycles or the same molecules or pathways getting involved,” Kshitiz said.
Future directions for the lab will involve gaining a better understanding of the “cheater” populations, the ways they communicate with other cells, and their effects on the cancer as a whole.
