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

faculty research

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|

Calendar Highlights: March 25, 2015

nuclear-conference-posterNuclear Weapons and National Security: SMU’s John Goodwin Tower Center for Political Studies hosts “Nuclear Weapons and National Security: The Once and Future Role of the Bomb” on Thursday, March 26, 5:30-7:30 p.m., in Elizabeth Perkins Prothro Hall. Featuring the recently retired commander of the U.S. Strategic Command and one of the country’s leading historians of the nuclear age, the program will examine the paradox of nuclear weapons and national security in the “post-nuclear” age. While the event is free and open to the public, but reservations are required. 

Exercise and Wellness Colloquium: SMU’s Department of Applied Physiology and Wellness presents Dr. Tim Church as he leads Research on Exercise and Wellness Colloquium Series on Friday, March 27, from 2-3:20 p.m. in R138 Simmons Hall. Pulling from his research on preventative medicine, Dr. Church will explore the hows and whys of an effective exercise plan. For more information, email Dr. Lynn Romejko Jacobs.

Table of Content Award Dinner: Friends of the SMU Libraries hosts Tables of Content featuring the presentation of the 6th Annual Literati Award to Willard Spiegelman on Saturday, March 28, 6 p.m., at the Collins Executive Education Center. Honoring individuals who have used the written word to advance the ideals of creativity, conviction, innovation and scholarship, the event features roundtables of engaging discussion with fascinating table hosts on a variety of topics. For ticket and sponsorship information, call 214.768.3225.

The State of the Data Center Industry: SMU’s Lyle School of Engineering hosts The State of the Data Center Industry featuring Chris Cosby, founder and CEO of Compass Datacenters. As the data center industry is continually evolving, Crosby will provide a detailed overview of the data center business. The seminar will take place on Monday, March 30, 2-3 p.m., in the Palmer Conference Center, Caruth Hall.

Meadows at the Meyerson: SMU’s Meadows School of the Arts hosts its 22nd annual benefit concert, “Meadows at the Meyerson 2015,” on Tuesday, March 31, at 8 p.m., at the Morton H. Meyerson Symphony Center in the Dallas Arts District. The annual concert features the critically acclaimed Meadows Symphony Orchestra and honors a community leader. This year’s honoree is noted arts and civic leader (and SMU trustee) Caren Prothro. Tickets to the concert are $17 for SMU students, faculty and staff.

March 25, 2015|Calendar Highlights, News, Save the Date|

Research: Whale fossil provides key to unlock date of East Africa’s mysterious uplift

A 17 million-year-old Turkana ziphiid beaked whale fossil from the Great Rift Valley, East AfricaPaleontologists have used a fossil from the most precisely dated beaked whale in the world to pinpoint for the first time a date when East Africa’s mysterious elevation began.

The 17 million-year-old fossil is from the Ziphiidae family. It was discovered 740 kilometers inland at a elevation of 620 meters in modern Kenya’s harsh desert region and is the only stranded whale ever found so far inland on the African continent, said SMU vertebrate paleontologist Louis Jacobs.

Uplift associated with the Great Rift Valley of East Africa and the environmental changes it produced have puzzled scientists for decades because the timing and starting elevation have been poorly constrained. Determining ancient land elevation is very difficult, but the whale provides one near sea level.

“It’s rare to get a paleo-elevation,” Jacobs said, noting only one other in East Africa, determined from a lava flow.

At the time the whale was alive, it would have been swimming far inland up a river with a low gradient ranging from 24 to 37 meters over more than 600 to 900 kilometers, said Jacobs. He is co-author of a study, published in the Proceedings of the National Academy of Sciences, that provides the first constraint on the start of uplift of East African terrain from near sea level.

“The whale was stranded up river at a time when east Africa was at sea level and was covered with forest and jungle,” Jacobs said. “As that part of the continent rose up, that caused the climate to become drier and drier. So over millions of years, forest gave way to grasslands. Primates evolved to adapt to grasslands and dry country. And that’s when – in human evolution – the primates started to walk upright.”

Identified as a Turkana ziphiid, the whale would have lived in the open ocean, like its modern beaked cousins. Ziphiids, still one of the ocean’s top predators, are the deepest diving air-breathing mammals alive, plunging to nearly 10,000 feet to feed, primarily on squid.

In contrast to most whale fossils, which have been discovered in marine rocks, Kenya’s beached whale was found in river deposits, known as fluvial sediments, said Jacobs, a professor in the Roy M. Huffington Department of Earth Sciences of SMU’s Dedman College of Humanities and Sciences.

The whale, probably disoriented, swam into the river and could not change its course, continuing well inland.

“You don’t usually find whales so far inland,” Jacobs said. “Many of the known beaked whale fossils are dredged by fishermen from the bottom of the sea.”

The beaked whale fossil was discovered in 1964 by J.G. Mead in what is now the Turkana region of northwest Kenya. Mead, an undergraduate student at Yale University at the time, made a career at the Smithsonian Institution, from which he recently retired. Over the years, the Kenya whale fossil went missing in storage.

Jacobs, who was at one time head of the Division of Paleontology for the National Museums of Kenya, spent 30 years trying to locate the fossil. His effort paid off in 2011, when he rediscovered it at Harvard University and returned it to the National Museums of Kenya.

The fossil is only a small portion of the whale, which Mead originally estimated was 7 meters long during its life. Mead unearthed the beak portion of the skull, 2.6 feet long and 1.8 feet wide, specifically the maxillae and premaxillae, the bones that form the upper jaw and palate.

The researchers reported their findings in “A 17-My-old whale constrains onset of uplift and climate change in east Africa” online at the PNAS web site. Besides Jacobs, other authors from SMU are Andrew Lin, Michael Polcyn, Dale Winkler and Matthew Clemens.

From other institutions, authors are Henry Wichura and Manfred R. Strecker, University of Potsdam, and Fredrick K. Manthi, National Museums of Kenya.

Funding for the research came from SMU’s Institute for the Study of Earth and Man and the SMU Engaged Learning program.

Written by Margaret Allen

> Read the full story from the SMU Research blog

March 19, 2015|For the Record, News, Research|

Calendar Highlights: Feb. 18, 2015

Emanuel Cleaver II

Emanuel Cleaver II visits Perkins Chapel as a guest preacher on Thursday,, Feb. 19th.

The Cultural Realities of Cancer: Visiting SMU under the Department of Anthropology, Dr. Deborah O. Erwin, Director of the Office of Cancer Health Disparities Research at the Roswell Park Cancer Institute, will explore “The Cultural Realities of Cancer” and how individuals are impacted by this diagnosis. This free event will take place in the McCord Auditorium on Wednesday, Feb. 18 at 5 p.m. For more information, email Pamela Hogan.

Emanuel Cleaver II: Sponsored by the Perkins School of Theology Black Seminarians Association, U.S. Representative and United Methodist clergyman Emanuel Cleaver II will visit the Perkins Chapel as a guest preacher on Thursday, Feb. 19, at 11:30 a.m., during the regular worship service. Celebrating Black History Month, the theme for this worship service is “We’ve Come This Far by Faith and We Won’t Stop Now!” For more information about the chapel service and Rev. Cleaver’s visit, email Ailey Pope, the chair of the Black Seminarians Association at Perkins.  

Godbey Lecture Series: In honor of the 800th anniversary of the Magna Carta, the Godbey Lecture Series presents “Perspectives on Magna Carta” featuring three SMU professors as they illuminate the history and contribution of the document. The SMU professors include; Jeremy Q. Adams, Professor of History, Joshua Tate, Associate Professor of Law, and Ada-Maria Kuskowski, Assistant Professor of History. The event will take place on Thursday, Feb. 19, 5:30 p.m. in the Gene and Jerry Jones Great Hall, Meadows Museum. While the lecture is free and open to the public, guests are asked to please register online. For more information, visit the Dedman College Interdisciplinary Institute webpage or email Elizabeth Fieldling. 

Meadows Virtuosi Players: SMU Meadows School of the Arts presents “Meadows Virtuosi Players” on Saturday, Feb. 21, at 6:30 p.m., in the Caruth Auditorium. Formed in 2012, the Meadows Virtuosi Players concert series features select Meadows student musicians performing side-by-side with their faculty colleagues. This Saturday, directors Andrés Diaz and Matt Albert will be joined by Meadows voice faculty member Camille King. For more information, call 214.768.2787.

Doris Kearns Goodwin

Doris Kearns Goodwin

Tate Lecture Series: SMU’s Willis M. Tate Distinguished Lecture Series presents Doris Kearns Goodwin, on Tuesday, Feb. 24. Goodwin is a Pulitzer Prize-winning biographer, best-selling author and presidential historian. While The Anita and Truman Arnold Lecture is already sold out, SMU students, faculty and staff are welcome to participate in the Turner Construction/Wells Fargo Student Forum at 4:30 p.m. in the Hughes-Trigg Student Center Ballroom. 

Research Day 2015: On Wednesday, Feb. 25, SMU graduate and undergraduate students are invited and encouraged to present results of ongoing and completed SMU-based research. Guests are welcomed to meet over 160 students engaged in research, and discover opportunities for future collaboration and entrepreneurship. The event will take place in the Hughes-Trigg Student Center, Promenade Ballroom, from 2-5 p.m. For additional information, view the 2015 Research Day Catalog or email Sarah Sage. 

February 18, 2015|Calendar Highlights, News, Research, Save the Date|

Calendar Highlights: Feb. 12, 2015

10868212_10152652457101981_2527087539809194370_n“The Search for Humanity:” As part of SMU’s Meadows School of the Arts Friday Morning Lecture Series, Dr. Luis Martin, Professor Emeritus of History, will present a lecture entitled “The Search for Humanity” on Friday, Feb. 13 at 10:30 a.m. in the Bob Smith Auditorium, Meadows Museum. For more information, call 214.768.7787. 

Museum Friday Gallery Talk: The SMU Meadows Museum hosts the Museum Friday Gallery Talk featuring “Joaquin Mir’s Allegory” on Friday, Feb. 13 at 12:15 p.m. Free to SMU students, faculty and staff, the Meadows Museum Gallery Talks feature art research and perspectives from local guest speakers and students. For more information, call 214.768.4677.

ESPN GameDay: ESPN College GameDay Covered by State Farm will make its first visit to SMU’s Moody Coliseum on Saturday, Feb. 14, prior to SMU’s home game against defending national champion Connecticut at 8 p.m. For additional information, visit the SMU Mustangs Men’s Basketball webpage.

Native American, Grammy Award-Winning singer songwriter Joanne Shenandoah.

Native American, Grammy Award-Winning singer songwriter Joanne Shenandoah.

Joanne Shenandoah: Sponsored by SMU’s Dedman College Interdisciplinary Institute, Grammy Award-winning singer songwriter Joanne Shenandoah will perform a free concert on Saturday, Feb. 14 at 7 p.m. in the Hughes-Trigg Theater. For more information and to register, visit the Dedman College Interdisciplinary Institute webpage. 

Stagger LeeThe Dallas Theater Center production of SMU Artist-in-Residence Will Power‘s new musical Stagger Lee will come to an end on Sunday, Feb. 15. Originally premiering in January as part of Will Power’s Meadows Prize residency, Stagger Lee was partially developed in workshops in collaboration with the Meadows School of the Arts. Tickets for Stagger Lee are available for purchase online. 

Coping with Immigration in Germany: From Ignorance to Acceptance?: SMU Dedman College of Humanities & Sciences presents Uwe Hunger in a lecture entitled “Coping with Immigration in Germany: From Ignorance to Acceptance?” on Monday, Feb. 16 at 3 p.m. in the Tower Center Boardroom, Carr Collins #227. Hunger is an Associate Professor of Political Science from Muenster University in Germany. While this is a free event open to SMU students, faculty and staff, guests are encouraged to RSVP via email to the Tower Center. 

Faculty Chamber Music Recital: SMU Meadows School of the Arts presents Liudmila Georgievskaya in the Faculty Chamber Music Recital on Tuesday, Feb. 17 at 8 p.m., in Caruth Auditorium. Acclaimed pianists Georgievskaya and Thomas Schwan will give a two-piano recital with Otto Singer’s rarely performed transcriptions of two of Mozarts great works, the Symphonies No. 40 and 41. For more information, call 214.768.2787.

logoFrom Columns to Characters: The Presidency and Press in the Digital Age: Scholars and journalists experienced in the effects of today’s digital reality will visit SMU to examine the evolving nature of the presidency and the press in all-day conference on Tuesday, Feb. 17. While the conference is free and open to the public, guests are encouraged to register online. For more information regarding the conference and conference participants, click here.

 

February 13, 2015|Calendar Highlights, Sports|
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