Research: Computer model of key protein helps predict how cancer drugs will work

Biology

Research: Computer model of key protein helps predict how cancer drugs will work

Drugs important in the battle against cancer behaved according to predictions when tested in a computer-generated model of P-glycoprotein, one of the cell’s key molecular pumps.

The new model allows researchers to dock nearly any drug in the P-gp protein and see how it will actually behave in P-gp’s pump, said Associate Professor John G. Wise, lead author on the journal article announcing the advancement and a faculty member in SMU’s Department of Biological Sciences, Dedman College of Humanities and Sciences.

SMU biologists developed the computer generated model to overcome the problem of relying on only static images for the structure of P-gp. The protein is the cellular pump that protects cells by pumping out toxins.

But that’s a problem when P-gp targets chemotherapy drugs as toxic, preventing chemo from killing cancer cells. Scientists are searching for ways to inhibit P-gp’s pumping action.

“The value of this fundamental research is that it generates dynamic mechanisms that let us understand something in biochemistry, in biology,” Wise said. “And by understanding P-gp in such detail, we can now think of ways to better and more specifically inhibit it.”

The SMU researchers tested Tariquidar, a new P-gp inhibitor still in clinical trials. Inhibitors offer hope for stopping P-gp’s rejection of chemotherapeutics by stalling the protein’s pumping action. Pharmacology researchers disagree, however, on where exactly Tariquidar binds in P-gp.

When run through the SMU model, Tariquidar behaved as expected: It wasn’t effectively pumped from the cell and the researchers observed that it prefers to bind high in the protein.

“Now we have more details on how Tariquidar inhibits P-gp, where it inhibits and what it’s actually binding to,” Wise said.

Written by Margaret Allen

> Read the full story from the SMU Research blog

September 22, 2015|Faculty in the News, Research|

Noted brain researcher Santosh D’Mello joins SMU as Biological Sciences chair

Santosh D’Mello

Santosh D’Mello, a respected scientist whose research is centered on understanding the molecular mechanisms regulating neurodegeneration, has joined SMU as professor and chair of the Department of Biological Sciences in Dedman College of Humanities and Sciences, effective Tuesday, April 1, 2014.

D’Mello comes to SMU from the University of Texas at Dallas, where he was a professor in the Department of Molecular and Cell Biology. He is a longtime partner in research with SMU Professor of Chemistry Edward Biehl.

In December 2010, D’Mello and Biehl published in The Journal of Neuroscience Research their discovery of a family of small molecules that shows promise in protecting brain cells against nerve-degenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s.

“Professor D’Mello brings broad experience and an excellent record as a researcher and teacher to SMU,” said Dedman College Dean Bill Tsutsui.  “His focus on building meaningful collaborations and his ambitious vision for the future of the Department of Biological Sciences impressed all of us on campus.”

D’Mello received his Ph.D. in biology from the University of Pittsburgh in 1989 and joined the faculty at UTD in 1998. Funding for his research has included support from the National Institutes of Health, the U.S. Department of Defense, the National Science Foundation and the Whitehall Foundation.

“Neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, ALS, and Huntington’s disease, are characterized by the slow but relentless loss of brain cells,” D’Mello said.  “There are no effective drugs or other therapeutic approaches to treat or prevent these progressive and fatal diseases. The goal of my lab is to understand neurodegeneration at the molecular level so that effective therapies can be developed.”

D’Mello said he was drawn to SMU because of the University’s strengths in several areas of the arts, humanities, and sciences. “I was particularly attracted by the collegial and talented faculty in the biology department, their keen interest in solving important biological problems, and their strong commitment to the teaching and training of students,” D’Mello said.

“I am honored to be named Chair of the Department of Biological Sciences and am very excited about the opportunity,” D’Mello said.  “I look forward to working with the faculty, staff and students to build a strong multidisciplinary and collaborative research department with cutting-edge research performed by bright, talented, and motivated undergraduates, graduate students, and postdoctoral fellows.”

Written by Kimberly Cobb

> Read the full story from SMU News

April 8, 2014|News, Year of the Faculty|
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