by Lori Oliwenstein Ebrahim Zandi, Ph.D., assistant professor of molecular microbiology and immunology, has been named one of just 20 Pew Scholars in the Biomedical Sciences for 2001. He is the first Pew Scholar to be named at the Keck School of Medicine of USC.
Administered by The Pew Charitable Trusts, a Philadelphia-based national philanthropy, the award aims to "nurture outstanding young scientists to become leading investigators at the forefront of their fields," says Rebecca W. Rimel, president of The Pew Charitable Trusts. Zandi, one of the USC/Norris Comprehensive Cancer Center's standout junior scientists, will receive $240,000 over four years to support his research.
There were 120 nominees for the 20 awards. The scholars were chosen by a 16-member national advisory committee that was chaired by Nobel laureate Torsten N. Wiesel, president emeritus of the Rockefeller University. Wiesel also chairs the External Advisory Committee for the Keck School's Neurogenetic Institute.
"Probably the most important aspect of this award," says Zandi, "is that my research is being recognized by a panel of high-caliber scientists."
Zandi's work focuses primarily on signal transduction, one of the central areas of study in biology. Signal transduction is the cascade of events that is set off when an enzyme, hormone or other chemical messenger docks in a receptor on the outside of a cell. An example would be an infection that is detected by a receptor on the surface of a cell, setting off an immune reaction to combat the infection.
The ultimate goal of the cascade of events is to turn on-or turn off-a gene in the cell's nucleus. In order to do that, the signal generated within the receptor at the surface of the cell is handed off from protein to protein-changing form, or transduced, along the way-until it reaches the nucleus. "I want to see, on a molecular level, just how the proteins transmit these signals from the cell surface to the nucleus," Zandi explains.
The best way to get that glimpse, he says, is to somehow reconstitute each of these protein transactions. He began this research before he arrived at USC/Norris, using a system called "NF-kappa B," short for nuclear factor kappa B (NF-kB). And it is what he will continue to work on with the flexible support he will receive as a Pew Scholar. Studies of NF-kB attract widespread interest in part because of the key role it plays in the HIV infection cycle.
NF-kB is a key transcription factor in setting up the process of inflammation, but when it is turned on continuously, it seems to prevent cell death, and so plays a role in cancer. Understanding just what happens in a cell to turn on NF-kB -and to keep it turned on-then, would be extremely useful in figuring out how to turn it off.
Toward that end, Zandi and his colleagues have taken several of the NF-kB signaling proteins, which are normally found only in mammals, and convinced them to set up shop in cultured yeast cells. (He chose yeast, he says, "because they're the simplest eukaryotic cells around, meaning cells with a true nucleus.") The yeast cells are simple to manipulate, which allows Zandi to do almost anything with the NF-kB system he wants to do-add a protein, subtract a protein, test a drug-and see what happens to the signal. "We're essentially using the yeast as our test tube," he explains.
"Finding the best system for a particular problem is really a challenge," he says. In this case, it was so challenging that Zandi has applied for a patent on the process.
And this sort of reconstitution is something, he says, that we will likely need to do over and over again, for as many of the signal transduction systems in our cells as possible. "We'll soon know the identity of every gene that there is in a cell," he notes, referring to the ongoing Human Genome Project and its map of all the DNA found in our chromosomes. "But the main question still remains: How do these things work within a cell to allow it to be alive?"