Nearly a fifth of all cancers contain the same genetic mutation, in a cellular complex that helps repair damage to DNA. This same mutation is common to all ovarian cancers.
It’s a defect in a complex inside cells that developed early in our evolutionary ancestry; so early that yeast cells contain the identical component. Now yeast are being used as a model organism to understand how this complex functions, as well as how it becomes impaired and fails to function correctly in cancer.
Prabodh Kapoor was recruited to join the faculty at the University of Texas Health Science Center at Tyler, from M.D. Anderson Cancer Center at Smithville, where he was a postdoctoral fellow. His appointment is in the department of cellular and molecular biology. A First-Time Tenure Track Award from CPRIT was used to retain this talented investigator in Texas.
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Nearly a fifth of all cancers contain the same genetic mutation, in a cellular complex that helps repair damage to DNA. This same mutation is common to all ovarian cancers.
It’s a defect in a complex inside cells that developed early in our evolutionary ancestry; so early that yeast cells contain the identical component. Now yeast are being used as a model organism to understand how this complex functions, as well as how it becomes impaired and fails to function correctly in cancer.
Prabodh Kapoor was recruited to join the faculty at the University of Texas Health Science Center at Tyler, from M.D. Anderson Cancer Center at Smithville, where he was a postdoctoral fellow. His appointment is in the department of cellular and molecular biology. A First-Time Tenure Track Award from CPRIT was used to retain this talented investigator in Texas.
The effects of the genetic mutations in the “Chromatin Remodeling Complex” are not well understood. But getting a better idea of how these mutations contribute to cancer may provide a new target for therapies to combat cancer.
Chromatin is the package inside a cell that contains all the genetic material needed to reproduce and create a daughter cell. The DNA is folded up so that it takes up less space inside the cell, but for any genetic process, like replication, the DNA has to be unfolded and then folded back up again.
The Chromatin Remodeling Complex is the master un-folder and re-folder. What appears to happen in normal cells is that during replication, it checks to make sure there is no DNA damage—like a laundress inspecting for holes or stains in clothing. Once the DNA damage is repaired, replication moves forward.
But if there is a defect in the Remodeling Complex itself, DNA damage is not repaired, and the “holes” and “stains” in the DNA are passed on to daughter cells. Acquired genetic defects in the complex may cause cells to proliferate uncontrollably, i.e. lead to cancer.
Kapoor is not only using yeast to study how the complex functions in normal cells, but also looking at genetically altered versions of the complex to see if there are any drugs that could stop it.
“We are very, very excited for what is going on right now in my lab,” Kapoor says.
Kapoor’s collaborators are using a combination of cryo-electron microscopy and computational simulations to better understand the structure of the normal and mutated complexes, especially looking for pockets in the structure that could bind inhibitors.
“This could lead to chemotherapies that could work in combination with other drugs,” Kapoor says, “which could be more efficient for the treatment of cancer.”
One of the advantages Kapoor sees in being at MD Anderson is that there are ovarian cancer cell lines in culture that can be used to test potential drug candidates.
Kapoor received his undergraduate and master’s degrees in biology and biochemistry, respectively, from the University of Lucknow, India; and his Ph.D. in molecular and structural biology from Jawaharlal Nehru University in New Delhi, India. He came to MD Anderson, Smithville, as a postdoctoral fellow in epigenetics and molecular carcinogenesis in 2010.
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