Scientist at Work: Manjari Mazumdar
The Indiana University School of Medicine's Medical Sciences Program in Bloomington welcomed a new researcher to its ranks earlier this year. Plucked from the prestigious National Cancer Institute, Manjari Mazumdar is bringing her cancer research to the halls of Bloomington's campus.
"Indiana University has always had a great reputation in biology," Mazumdar said, when asked what brought her to Bloomington. "Plus, other researchers and advanced equipment both here and at Indiana University-Purdue University Indianapolis (IUPUI) provide great opportunities for collaboration."
Mazumdar is one of thousands of researchers worldwide who investigate cancer and its numerous causes. Mazumdar's research centers on cancerous growths caused by the loss of a protein called chromokinesin.
Motor proteins like chromokinesin are found in all species of life that require interior, active transport of cellular materials to reproduce and grow. Every cell has a certain number of chromosomes -- 23 pairs for humans -- that contain the organism's genetic information coded in DNA. During cell division, chromosomes are duplicated, divided, and handed down from one mother cell to two new daughter cells. Chromokinesin plays an important role in the chromosomes' movement. The chromokinesin grabs the chromosomes and then pulls itself down long, rigid structures called microtubules. Microtubules radiate out from the center of the cell in such a way that chromosomes can be pulled by chromokinesin and other actors to opposite sides in preparation for cell division.
"These motor proteins are essential to cell division and hence genomic stability," said Mazumdar, who earned her doctorate and operated a lab in India before moving to America.
In a normal cell, the motor proteins help replicated chromosomes separate into equal halves so that the genetic make-up of the original cell is maintained in the new daughter cells. But what happens when a cell is missing this particular motor protein, or it somehow doesn't do its job?
According to Mazumdar, if biological "checks" miss an error in chromosome separation, and a cell with an unequal number of chromosomes survives, the result can be cancer.
"It appears that cells lacking this chromokinesin often have abnormal chromosome numbers or cell structures, which can lead to cancer," said Mazumdar. "Until a few years ago, there was a big debate over whether the unequal number of chromosomes can cause cancer, or if it is a consequence of the disease. My research has shown that when we delete the chromokinesin from the cells, it leads to unequal segregation of chromosomes, and subsequently cancer."
But no single abnormality leads to cancer by itself. It is a complex series of interactions in different metabolic pathways that is not yet fully understood. However, the loss of this single molecule, chromokinesin, appears to directly correlate to cancer development, which is a rare find. Mazumdar hopes to use her research at IU to develop this protein as a biomarker.
If tests show a patient lacks this specific motor protein, it could lead to the early detection of certain kinds of cancer, vastly improving the chance of recovery. If Mazumdar can learn how this molecule interacts with other proteins and molecules, and how its loss affects cell division, it may also lead to new cancer preventions and treatments.
"We're taking a bottom-up approach to cancer," said Mazumdar. "Can a molecule manipulate the genome enough to prevent cancer? If yes, how? What are the pathways that this molecule is involved in that are critical in preventing cancer, and can we find a small molecule to prevent the effects of the defects caused when this molecule is absent? These are just a few of our long-term goals."
