Revealing research: Kidney tumor analysis helps decipher proteins’ role in cancer development

The June issue of the global scientific journal Nature Communications features work by (pictured, from left) graduate student Diana Dunn; research assistant Mark Woodford; biochemist/molecular biologist Mehdi Mollapour, PhD; urologist Gennady Bratslavsky, MD; and assistant professor Dimitra Bourboulia, PhD. The research team also includes professor Stewart Loh, PhD; graduate student Adam Blanden and librarian Wendi Ackerman. (PHOTO BY ROBERT MESCAVAGE)

The June issue of the global scientific journal Nature Communications features work by (pictured, from left) graduate student Diana Dunn; research assistant Mark Woodford; biochemist/molecular biologist Mehdi Mollapour, PhD; urologist Gennady Bratslavsky, MD; and assistant professor Dimitra Bourboulia, PhD. The research team also includes professor Stewart Loh, PhD; graduate student Adam Blanden and librarian Wendi Ackerman. (PHOTO BY ROBERT MESCAVAGE)

BY AMBER SMITH

Some of the tumors Gennady Bratslavsky, MD, removes from patients’ kidneys are no bigger than olives. Some are the size of watermelons. Since July 2014, many have ended up in the laboratory of Bratslavsky’s research partner, Mehdi Mollapour, PhD.

After the surgeon removes the tumors, they are packaged on sterile ice in a cooler. A technician carefully transports the tissue from the operating room at Upstate University Hospital to the laboratory in adjacent Weiskotten Hall. There, Mollapour and laboratory members Mark Woodford and Diana Dunn dissect the tumors, extracting proteins from them for analysis.

It’s a classic example of “bench-to-bedside” research that typically occurs at an academic medical center such as Upstate. Doctors at a patient’s bedside collaborate with scientists at a laboratory bench, sharing a focused mission to gain particular knowledge. In this case, what Bratslavsky, Mollapour and colleagues have learned about a specific type of kidney cancer applies to all kidney cancers — and likely many other cancers as well.

Their initial work was on cells from people with Birt-Hogg-Dube syndrome. That is a rare, inherited cancer syndrome caused by a mutation of the gene FLCN, which predisposes people to form kidney tumors, pulmonary cysts and benign skin tumors.

Bratslavsky chairs the urology department at Upstate. Mollapour, an assistant professor of urology, leads the renal cancer biology section of the urology department.

Their team deciphered the complex relationship between FLCN and some crucial proteins, one called Hsp90 and a pair called FNIP 1 and FNIP 2 that watched over and exerted influence on Hsp90. The proteins’ interactions affect processes that take place within cancer cells that are forming, at a time so early in development that their existence cannot be detected through available testing.

“One of the biggest things that has been shown with this research is that control of Hsp90 is extremely precise,” Mollapour says. While their work on the tumors continues, the research team’s 15-page paper — which appears in the June issue of Nature Communications, a global scientific journal —  details how Hsp90 is controlled.

That’s particularly encouraging because Hsp90 is found in all cancer cells, not just kidney cancer cells. Learning how to manipulate this protein could lead to improved cancer treatment.

Consider someone with cancer who takes a drug but sees no effect. The drug may not work simply because it cannot gain entry to the cancer cells.

Or, consider someone who cannot tolerate a cancer drug because of debilitating side effects. It may be because too much of the drug is getting into healthy cells.

In both cases, regulation of the Hsp90 protein might help the drugs work better.

Drugs already in clinical trial are being tested for their ability to inhibit Hsp90, Bratslavsky says. And, it turns out, greater levels of the drugs accumulate in cancer cells when levels of the FNIP proteins are high.

It’s promising research, which only began because an Upstate surgeon decided to team up with a laboratory scientist to investigate a rare syndrome.

Layout 1This article appears in the winter 2017 issue of Cancer Care magazine

 

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