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winter 2013

research at

north carolina central university

A laser sorts cells and tissue — part of the drug-development process at BRITE


winter

2013 r e s e a r c h

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Research News

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winter 2013

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Finding The Needles In The Haystack north carolina central university

A laser sorts cells and tissue — part of the drug-development process at BRITE

on the cover

Dr. Jonathan Sexton uses laser technology to sort cells from tissue in his laboratory at NCCU’s Biomanufacturing Research Institute and Technology Enterprise (BRITE).

Tackling A Sexually Transmitted Superbug And Communities Of All Sizes The gonorrhea bacteria has

Using BRITE’s array of

developed resistance to

advanced tools, Jonathan Sexton

antibiotics: Daniel Williams is

develops drugs to treat diabetes.

exploring new lines of attack.

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Gangs Are Everwhere—And Denial is No Solution

Advocating For Young Black Readers

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How Can Materials Be Smart? Chemist Darlene Taylor’s

molecular manipulations create objects with intelligence

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Cutting Off Cancer’s Communication Lines Antonio Baines looks

for ways to disrupt a killer’s biochemical processes

Wendy Rountree seeks a higher

A police-officer-turned-academic

profile for African-American

presents an inconvenient truth

literature for children and teens

to—parents, school systems, police departments and communities of all sizes.

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Photo by Ted Richardson.

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Ceftriaxone clinical failure


Highlighting Our Discoveries

adminis t rat ion: chancellor Charles L. Becton

Dear Friends of NCCU:

contributors

vice chancellor of research and economic development

I am pleased to introduce Quest, a magazine focusing on the research performed at North Carolina Central University. Research and scholarship have always been a vital part of the mission here at NCCU, even in this university’s earliest days. Today, the university boasts two major research institutes that focus on health disparities and drug discovery and a new science complex. These modern facilities and laboratories are equipped with state-of-the-art equipment. Our highly qualified professors and researchers are securing patents and developing new drugs. They are making discoveries and opening new areas of inquiry in the sciences, social sciences and liberal arts. Evidence of that momentum can be found in the support our research has drawn from sponsors such as the National Science Foundation and the National Institutes of Health. The total value of sponsored research grants has increased from $9.3 million in 2007 to more than $25 million in 2011. From fiscal year 2007 through 2012, the university has received nearly $120 million in sponsored research support. NCCU researchers have filed seven provisional patents; an eighth patent, for a carbon nanotube oscillator surface-profiling device, was issued November 2011 (see article, Page 9). One area of emphasis in our research is health disparities — the profound gaps in health status that exist between America’s racial and ethnic minorities and the population as a whole. In fact, three of the researchers whose work is highlighted in this issue are engaged in finding causes and treatments for diseases and conditions that disproportionately affect African-Americans. Dr. Antonio Baines is expanding human knowledge about the sequence of molecular events that lead to pancreatic cancer. Dr. Darlene Taylor is developing more effective treatments for uterine fibroids, the most common gynecologic tumor among women of childbearing age. Dr. Jonathan Sexton is developing drugs to treat type 2 diabetes. We’re proud of the work being done by these and other researchers, and proud to share it with you in this inaugural issue of Quest.

Hazell Reed provost and vice chancellor of academic affairs

Debbie Thomas Susan Hester

Hazell Reed Vice Chancellor for Research and Economic Development

in genetics and molecular biology from UNC-Chapel Hill. She has written about a broad range

vice chancellor of institutional advancement

Lois Deloatch

of subjects for publications of the UNC School of Medicine, Duke University Medical Center,

vice chancellor of finance and administration

the Mayo Clinic, The News & Observer and Charlotte Observer, and other organizations.

Wendell Davis

Tiffany Slaybaugh DaVanzo (illustrations) specializes in art for medical publications,

vice chancellor of student affairs and enrollment management

kevin rome

education and the medical legal field. She is a Certified Medical Illustrator and a graduate of the

director, biomedical/biotechnology research institute (bbri)

K. Sean Kimbro

Art as Applied to Medicine program at the Johns Hopkins University School of Medicine.

director, biomanufacturing research institute and technology enterprise (brite)

Ted Richardson (photography) is a photojournalist based in Chapel Hill. A former staff

Li-An Yeh

photographer for The News & Observer in Raleigh, he has taught courses in photojournalism at

director, office sponsored research and programs

Edith Hubbard

UNC-Chapel Hill. He received Photographer of the Year awards from the N.C. Press Association in

director, office of research compliance and technology transfer

Undi N. Hoffler

2007 and from the N.C. Press Photographers' Clip Contest in 2006. He has a bachelor’s degree

cont ribu t ors : editors: Rob Waters, Ayana D. Hernandez

from Davidson College and a master’s degree in journalism from UNC-CH.

design and layout:

Pandora Frazier

photography and illustration: Ted Richardson, Robert Lawson, Tiffany DaVanzo writers:

marla vaseck broadfoot, Rob Waters

quest is published by the Office of Research and Economic Development at North Carolina Central University. Send comments, requests for permission to reprint material and requests for additional copies to: Office of Public Relations 118 William Jones Building / P.O. Box 19617 Durham, NC 27707 / Phone: 919-530-6295 Email: publicrelations@nccu.edu nccu is accredited by the commission on colleges of the southern association of colleges and Schools to award baccalaureate, master’s, education specialist, and doctoral degrees. contact the commission on colleges at 1866 Southern Lane, Decatur, ga 30033-4097 or call 404-679-4500 for questions about the accreditation of nccu.

Sincerely,

Marla Vacek Broadfoot, Ph.D., (writer) is a science writer and editor who holds a doctorate

vice chancellor and chief of staff

april 17-19 2013

NCCU Health Disparities Conference Pursuing Health Equity Through Translational Research and Partnerships Durham Convention Center I www.nccu.edu/healthdisparities

North Carolina Central University I Division of Research and Economic Development

Copyright 2012, North Carolina Central University

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research NEWS

NCCU PHYSICIST’S TEAM GETS PATENT FOR HIGH-TECH Carbon nanotubes get their name from their long, hollow SCANNING DEVICE structure, with walls formed by one-atom-thick sheets of carbon

BBRI Receives $5.7 million NIH Grant for Health Disparities Projects

K. Sean Kimbro, Ph.D.

Mildred A. Pointer Ph.D., FAHA

North Carolina Central University’s Julius L. Chambers Biomedical/Biotechnology Research Institute (BBRI) has received a National Institute of Minority Health and Health Disparities (NIMHD) Exploratory Center of Excellence grant for $5.7 million. Originally funded in 2002 as Project EXPORT, this is a five-year competitive renewal of the longest-funded National Institutes of Health (NIH) grant at BBRI. Research involving health disparities — the gaps between the health status of racial and ethnic minorities compared with the population as a whole — is explicitly part of BBRI’s mission, and the projects funded by the NIH grant all focus on cardio-metabolic diseases that disproportionately affect African-Americans. The projects will be administered by the newly named Center for Translational Health Equality Research (CTHER), led by K. Sean Kimbro, Ph.D., director of BBRI, and Mildred A. Pointer, Ph.D., FAHA, associate professor. CTHER consists of four key projects:

Adiponectin in Cardio-metabol-

Calcium in Metabolic Syndrome:

ic Health Disparities: Sujoy Ghosh, Ph.D., senior scientist, will lead an investigation of the role of adiponectin, a substance that helps the body regulate insulin, in health disparities. Low levels of adiponectin are associated with diabetes and obesity.

Emmanuel Awumey, Ph.D., assistant professor and research scientist, and Mildred Pointer, Ph.D., FAHA, both in the CardioMetabolic Research Program at BBRI, will lead an investigation of the role of calcium in diabetes, hypertension and obesity. This project will combine laboratory and community approaches, conducted by the Community Engagement group, to gain a better understanding of the role of calcium in these diseases.

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Training and Education: Saundra Delauder, Ph.D., associate professor of chemistry, will direct a project to support minority students in health disparities research. The aims are to recruit and increase the number of future health disparities researchers from the fields of biomedical sciences, nursing, psychology, and public health education. Community Engagement: Natasha Greene Leathers, Ph.D., RN, FNP, BC, assistant professor of nursing, will oversee community-based culturally sensitive interventions aimed at helping African-American communities in Halifax County, N.C., and surrounding counties to adopt healthy behaviors. This project will develop a partnership between a rural population and academic researchers to evaluate and refine a family-focused intervention for AfricanAmericans with Type 2 Diabetes. “For the renewal of this grant, we targeted diseases that profoundly impact minority communities,” BBRI director Kimbro said. “With an investment of approximately $5 million over five years, the National Institutes of Health and the scientific community have given a strong statement of support and confidence in our research.” Pointer emphasized the translational aspect of the projects — finding ways to use the research to directly improve health outcomes. “We really wanted to combine expertise from the various disciplines to make sure that our research conclusions can be directly applied in North Carolina communities,” she said. “This ‘bench-to-curbside’ philosophy is at the heart of CTHER.” CTHER will partner with organizations and communities to conduct these four projects, working toward an ultimate goal of eliminating cardio-metabolic health disparities. BBRI is part of NCCU’s Division of Research and Economic Development.

Dr. Igor V. Bondarev,

associate professor of physics at North Carolina Central University, and two other scientists at the University of South Florida have been awarded a patent for a device to scan extremely smooth surfaces to identify the tiniest flaws. The device, called a carbon nanotube oscillator, is designed to improve on the performance of an existing tool called the atomic force microscope. The carbon nanotube oscillator device has a wide range of potential applications in places where extremely smooth surfaces are needed, or where one needs to determine a detailed structure of the local surface roughness pattern — in industrial, research and university laboratories and in manufacturing. “When you need an extremely clean, flat solid surface, you can never get it, even if you polish,” Bondarev says. “Our device is able to sense surface roughness with a resolution that is two to three orders of magnitude better than that of currently available atomic force microscopes. That will make it possible to sort out ‘dirty’ sample surfaces from ‘clean’ ones. Our device can also be used to study surface roughness patterns at a nanometer-scale resolution.” “The new machine does not yet physically exist,” Bondarev emphasizes. “The patent is for the idea — the concept.” But there is good reason to think the oscillator has the potential to improve significantly on the performance of atomic force microscopes currently in use. Many thousands of such microscopes are employed in laboratory and industrial settings around the world, and they range in price from $20,000 to more than $1 million. Sharing in the patent with Bondarev are his long-term collaborators, University of South Florida physicists Adrian Popescu and Lilia Woods. The three scientists are named as the inventors, and the patent is assigned to their respective universities.

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called graphene. They are among the stiffest and strongest fibers known, with remarkable electronic properties and other unique characteristics, and they have attracted huge academic and industrial interest. In atomic force microscopes, a tiny, needle-like piece of metal functions as a mechanical probe, “feeling” the surface in question to detect flaws. The carbon nanotube oscillator device developed by Bondarev and his USF collaborators replaces the metal piece with a double-walled carbon nanotube oscillator in which one cylindrical nanotube is contained and is moving within another one of slightly larger diameter. The device will be able to measure a given surface profile at a resolution on the order of one nanometer — one billionth of a meter. A single molecule of water has a size of slightly less than one nanometer; a human hair is about 100,000 nanometers thick. The technology for creating carbon nanotubes is changing rapidly, Bondarev said, and it may well become feasible to build the new device for less than it costs to build a conventional atomic force microscope. Any commercial payoff from the patent is likely to be years away. Dr. Undi Hoffler, NCCU’s director of research compliance, said that NCCU and the Florida university expect to explore options for licensing the concept to a manufacturer, and that future profits would be divided among the universities and the inventors. “This is a long-term prospect,” Hoffler said, “but this invention should stand for awhile.” Bondarev joined the NCCU physics faculty in 2005. He is a native of Belarus, the former Soviet republic. He holds a master’s degree and Ph.D. from the Belarusian State University in Minsk, and a Doctor of Science (D.Sc.) degree in theoretical solid-state physics from the National Academy of Sciences of the Republic of Belarus. The D.Sc. degree is awarded to less than 1 percent of active former Soviet Union scientists who hold the Ph.D. Bondarev said he will be pleased to see the machine he helped conceive become reality. “I’m a theoretical physicist. I've done my part of the job,” he said. “The experimentalists now need to build it and use it.”

nccu


research NEWS

Howard Hughes Medical Institute Grant Will Support Undergrad Biology Research

‘‘

This grant will allow NCCU to revolutionize our biology curriculum with state-of-the-art teaching, including innovative mechanisms delivered through research modules in the classroom.” — dr. sandra L. white

NCCU will receive a $1.4 million grant from the Howard Hughes Medical Institute (HHMI) over four years to support undergraduate research experiences and increase the number of students who are attracted to the sciences. The funding is intended to introduce research to all biology majors through a research-focused lab modeled after the HHMI–Science Education Alliance, assist faculty in developing curriculum revisions that will permit research, and create an interactive learning environment for nonmajor courses so students are equipped to be scientifically curious and critical thinkers. “What happens during the undergraduate years is vital to the development of the student, whether she will be a scientist, a science educator, or a member of society who is scientifically curious and literate,” said Sean B. Carroll, HHMI’s vice president of science education. “HHMI is investing in NCCU and other schools because they have shown they are superb incubators of new ideas and models that might be replicated by other institutions to improve how science is taught in college.” “This grant will allow NCCU to revolutionize our biology curriculum with state-of-the-art teaching, including innovative mechanisms delivered through research modules in the classroom,” said Dr. Sandra L. White, director of the Center for Science, Math and Technology Education at NCCU. “This is an important opportunity to learn how to effectively provide all students with a course-based authentic research experience.” The initiative will be led by Dr. White and Dr. Gail Hollowell, assistant professor in NCCU’s department of biology.

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Study Offers New Data on How Indoor Insecticide Spraying Cuts Malaria Infections A study by researchers at North Carolina Central University and Duke University offers new evidence supporting indoor insecticide spraying as a way to sharply reduce malaria deaths. In the most comprehensive review to date of the effectiveness of indoor insecticide treatments, a team led by Dohyeong Kim, Ph.D., associate professor in NCCU’s Department of Public Administration, found that over the last decade, the treatments have reduced infections in communities with high rates of malaria by an average of 62 percent, despite rising insecticide resistance among mosquitoes. The investigators say the more important contribution of the study is its identification of factors — one of which is the use of the widely banned insecticide DDT — that appear to influence the success of indoor residual spraying (IRS). Their review was published in the July issue of The American Journal of Tropical Medicine and Hygiene. Kim and his Duke co-authors, Kristen Fedak and Randall Kramer, conducted a meta-analysis — a form of research that synthesizes the results from previous studies — of 13 peer-reviewed

reports published between 2000 and 2010 that considered how IRS affects malaria transmission in various settings, mostly in Africa. IRS involves coating the walls of homes or community buildings with insecticides in an effort to curb infections by killing malaria-carrying mosquitoes. “Our findings show that during the last decade IRS has remained a powerful tool for fighting malaria, even though mosquitoes, particularly in Africa, are developing the ability to evade widely used insecticides,” Kim said. It is widely accepted that IRS can significantly reduce malaria infections, Kim said, but what is less known are the factors that can influence the extent of success. The researchers found that IRS appears to be best at reducing malaria infections in areas experiencing a high rate of disease and where there is a threat from both Plasmodium falciparum parasites — the most deadly form of the disease — and Plasmodium vivax parasites. The IRS campaigns were found to be more effective if they involved several rounds of spraying. Another factor that appeared to improve IRS effectiveness was the use of DDT. “Our (study) results show that DDT is more effective at reducing malaria prevalence than pyrethroids or other insecticides,” the authors state. Pyrethroids are the most widely used class of insecticides in IRS programs. But over the last decade mosquito populations in many malaria-endemic areas have developed traits that make them resistant to these compounds. DDT (dichlorodiphenyltrichloroethane) has been banned in the United States since 1972 and subsequently in many other countries over concerns about its toxicity to humans

and animals. Those dangers were primarily the result of widespread use of DDT in agricultural settings, however, and applications for IRS are small by comparison. Kim and his colleagues note that recent studies indicate that even at low levels, DDT may still be harmful to those exposed. But he said the study’s findings indicate that the advantages may outweigh the hazards in places where malaria transmission is particularly intense. The environmental dangers would need to be weighed against DDT’s potential to reduce malaria illnesses and deaths, he said.

east Asia have developed resistance to the drug. “Both of these studies demonstrate the incremental successes and long-term challenges faced by our drive to prevent needless deaths due to malaria,” said James W. Kazura, M.D., president of the American Society of Tropical Medicine and Hygiene, the organization that publishes the journal. “Make no mistake, this is a winnable battle. We can and will ultimately eradicate malaria from its strongholds in Africa and Asia.” Dohyeong Kim joined the NCCU faculty in 2008, one year after receiv-

In the most comprehensive review to date of the effectiveness of indoor insecticide treatments, a team led by Dohyeong Kim, Ph.D., associate professor in NCCU’s Department of Public Administration, found that over the last decade, the treatments have reduced infections in communities with high rates of malaria by an average of 62 percent, despite rising insecticide resistance among mosquitoes. — Dohyeong Kim, Ph.D. Kim and his colleagues note that the finding of substantial effectiveness (62 percent with considerable variation) for indoor spraying implies that mosquito control methods have “improved substantially during the past decade.” They also called for more studies that consider the effectiveness of IRS and insecticide-treated bed nets together to see whether “there is any additional benefit of combining” the two in the same households. The review by Kim’s group was one of two major articles about the battle against malaria in the July issue of The American Journal of Tropical Medicine and Hygiene. In the other study, scientists affirmed the effectiveness of a critical anti-malarial drug, Artesunate, in a West African malaria “hot zone,” even though malaria-carrying parasites in South-

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ing his doctorate in City and Regional Planning from UNC–Chapel Hill. A native of South Korea, he holds bachelor's and master's degrees in Public Administration from Yonsei University in Seoul.


Finding Needles in the Haystack Using BRITE’s array of advanced tools, Jonathan Sexton develops drugs to treat diabetes diabetes

by Marla Vacek Broadfoot

For decades the pharmaceutical industry relied upon an artificial, automated approach to discover new drugs. Scientists would create miniature environments inside thousands of test tubes, add a different potential drug to each, and then look for a specific “biochemical readout” that meant the drug was working. This technique, called high-throughput screening, produced many successes, but it also yielded many failures. For example, the diabetes drug Avandia, discovered in this manner, brought in $2.6 billion in 2006 but now carries an FDA “black-box” warning because of life-threatening side effects.

(Left) Sexton draws from BRITE’s small-molecule “library” to conduct tests on human tissue. (Top) The laser apparatus at BRITE is just one part of the technology Jonathan Sexton uses in his drug-discovery research. Containing more than a half-million compounds stored in refrigerators, it is one of the largest academically held compound collections anywhere. Photos by Ted Richardson unless otherwise noted. 11

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Today the industry has largely scrapped highthroughput screening in favor of other methods of drug discovery. One such method is being employed by Jonathan Sexton, Ph.D., an associate professor at NCCU’s Biomanufacturing Research Institute and Technology Enterprise (BRITE). Sexton has long felt that the pharmaceutical approach — which doesn’t mimic what happens to a drug inside a real human being — was doomed to fail. So he has spent the last six years developing his own drug discovery pipeline, using a method known as high-content screening, which relies on actual human cells and tissue that have been grown in petri dishes or taken from human cadavers. Working with real human samples is a huge technical challenge, but it also has the potential for huge payoffs.

says. “Now on a daily basis, I have to interface with all this laboratory automation, with robots, and the biology aspect, and surface science and the materials aspect. There’s even physics involved. I feel lucky that I landed in an area that allows me to utilize the interests I have in all these different disciplines.” Sexton has chosen to focus his career on an area involving what is arguably the greatest health risk to Americans today: type 2 diabetes. The disease once known as adult-onset diabetes now affects even our youngest citizens, with a recent Centers for Disease Control report indicating that 33 percent of children born in 2000 will develop diabetes in their lifetime. The 2011 CDC report contained another staggering prediction: that half of African-American women will eventually develop type 2 diabetes.

The solution to the drug discovery problem is to test more potential drugs, which means that we end up testing hundreds of thousands of compounds on human cells and human tissue. To manage those numbers we have to develop very sophisticated machine vision and pattern recognition algorithms and software to take a look at all of these pictures.” — Jonathan Sexton “Our drug discovery approach is much more valuable than conventional biochemical tests because we see a potential drug’s effect in actual human tissue,” Sexton says. “That means we have a much higher likelihood of translating that finding to an effective therapy. There is a shift in where drugs of the future are emerging. They are increasingly coming from biotechs or straight out of the university, like we are doing.”

A Worthy Target

Making discoveries that get rapidly translated into new treatments is the aim of Sexton’s research. From a very young age, Sexton says he “bounced around” from math to physics, chemistry, biology, engineering and materials science, never quite knowing where he should focus his attention. At the same time, the disciplines themselves were evolving, becoming less siloed and more interdisciplinary to address big scientific questions. Sexton began to see where he could fit in. “One area where all these distinct disciplines seemed to be coming together with a lot of harmony was translational medicine,” Sexton

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(Left) A tissue slide prepared by Sexton shows the islets of Langerhans area of a mouse pancreas, where insulin is secreted. The green stains are insulin. (Right) Sexton examines liver tissue for signs of fatty liver disease on a computer screen. He has identified compounds that reverse the disease in tests on animals. (Bottom) Multicolored laser light feeds into the cell sorter.

Existing diabetes medications often don’t prevent progression to dependence on daily injections of insulin. This progression occurs when specialized cells in the pancreas, called beta cells, become locked in a damaging cycle, secreting more and more insulin until they are simply worn out. “We can treat hyperglycemia, but it is really the progression that matters in terms of preserving those very special cells in the pancreas that secrete insulin,” Sexton says. “The long-term solution is clearly lifestyle change and reversing obesity, but in the short term we need drugs that halt this progression, and we don’t really have them. That is what my lab wants to find. The longer you can preserve those cells, the longer you can stave off some of the long-term complications.”

How It Works

To find these new drugs, Sexton first housed the special beta cells in incubators in his laboratory. Using bioimaging — a process that combines the functions of microscope, camera and computer — Sexton could see if the addition of drugs to the

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cells increased or decreased the production of insulin, or in the most common response, had no effect. The approach is deceptive in its simplicity. Because he often uses cells from human cadavers, Sexton has to account for the underlying differences between cells — and between human beings — as he begins to analyze his results. “It is incredibly challenging,” Sexton says. “The solution to the drug discovery problem is to test more potential drugs, which means that we end up testing hundreds of thousands of compounds on human cells and human tissue. To manage those numbers we have to develop very sophisticated machine vision and pattern recognition algorithms and software to take a look at all of these pictures. Because ultimately what we do is take pictures of cells and then categorize their response: Is it up, down or no effect? If you screen a thousand compounds, you may see one that is interesting, so it is definitely a needle in a haystack.”

Luckily, he doesn’t have very far to search, as BRITE happens to be the home of one of the largest academically held small-molecule collections. Any one of its half-million compounds — which Sexton likens to a “chemistry playground” — could represent a new treatment for diabetes or another pressing condition. Sexton, in fact, has already found a few needles in that hunt through the haystack. He has identified compounds that completely reversed fatty liver disease — which occurs in 80 percent of obese people with type 2 diabetes, in animal models of the illness. With a Phase-I Small Business Innovation Research grant from the NIH, Sexton is starting a company to spur the development of these compounds into a real drug. In a separate effort, he has partnered with a company in Research Triangle Park, Zen-Bio, to commercialize the platform itself so that other researchers can use it to uncover new therapeutics. “I am leveraging this work not only to enable more basic research to find better treatments for diabetes, but also to realize any commercial potential in the tools and drugs that we have discovered,” Sexton says. “And that helps fuel the research cycle as well.”

A police-officer-turned-academic presents an inconvenient truth to parents, school systems, police departments and communities of all sizes.

Paying It Forward

The desire to take his experimental platform beyond the confines of his laboratory fits well with Sexton’s self-ascribed “jack of all trades” label. From time to time, he still dabbles in other areas, working with Jay Brenman, Ph.D., at UNC-Chapel Hill to design a similar platform for identifying drugs for neurological disorders, or Kevin Williams, Ph.D. at NCCU, to uncover better treatments for inflammatory breast cancer. “Biology is so immense that we can only be masters in our own specific niches, but that doesn’t mean we have to let go of our interests in other therapeutic areas,” Sexton says. “By partnering with experts in these other areas, we can apply the tools we have developed — such as the chemical library and our high-content screening facility — to discover drugs for many different human diseases.” Q Four views of insulin: (A) mCherry-insulin fusion reporter system. (B) Endogenous insulin stained with an anti-insulin antibody. (C) Endogenous cellular insulin. (D) False coloring of different kinds of insulin inside the cell: White is newly synthesized insulin, red spots are insulin granules. Also visible are insulin granules docked at the plasma membrane awaiting release into the bloodstream. Images provided by Jonathan Sexton.

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Photo by Robert Lawson

Quite a bit of research shows that RICO prosecution is one of the most effective ways to actually remove gangs from a jurisdiction. It takes time and resources, and it requires collaboration between the local police and a federal prosecutor, but it allows you to take all the members of a gang rather than just a few people at the top who have others waiting to step up.” — DR. M. MICHAUX PARKER Dr. M. Michaux Parker is an assistant professor in the Public Administration Department who has also taught in the Criminal Justice Department. A graduate of NCCU, he worked as a police officer and gang specialist in Durham and elsewhere before pursuing advanced degrees in criminal justice. He has written extensively about gangs in the Journal of Gang Research, the American Journal of Criminal Justice and other publications. He explains some of his findings in a discussion with Rob Waters of the NCCU Office of Public Relations. Q. What are some of the big things the public doesn’t understand about gangs? Number one is that gangs are everywhere. It’s not an “over there” problem. But by treating it as just a big-city issue, we allow ourselves this comfort of not having to address it. The thinking in many communities seems to be, “If we address the problem, it means we’re a bad place — say, like

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Detroit — and we like to think of ourselves as much better.” But all places have gangs. When a community becomes a great place to live, it’s a great place for good people and a great place for bad people. A second thing is that gangs have been around since the beginning of time. The first American gang on record was in 1791. A Philadelphia newspaper that year warned citizens not to go out at night because there was a “criminal mob.” They called it a criminal mob, but it certainly met the definition of a gang — three or more people who had an ongoing association for the purpose of committing or promoting crime. I would also want people to know that gangs are very organized. It’s not like the Little Rascals. Sometimes I think we have that view for the same reason that we want to see gangs as mostly a large metropolitan area problem, But when we look at gangs for what they really are — having multimillion dollar incomes, being very organized with a clear structure and hierarchy — that scares us.

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Q. Research by you and others shows that children are drawn toward gangs when they’re quite young — not just in middle school but also in elementary school — and that kids this age should be the target of prevention efforts. Why do many communities and school systems resist intervening? Many parents feel that if their child is getting involved in gang-related activities, it means they’re bad parents. That’s not necessarily the case, but it’s the No. 1 stigma I see when I talk to parents about early intervention. They become angry — and they don’t want to believe that their child could be involved in a gang. They will give it a neutralizing definition. Yes, he has burned a gang brand into his arm with a cigarette lighter, but he doesn’t really know what it means. I’ve had parents tell me he did it by accident. Whatever a child does, the parent is usually the first to notice, but — because of denial — the last to know. So when you start to talk about early intervention, you meet resistance, because many parents have this assumption that it means “I’m a bad parent.” Q. And this unwillingness to face reality, aside from existing at a very basic individual and family level, carries over into schools and communities? Yes, schools and communities tend to resist facing gang problems for similar reasons. In some school systems, principals are evaluated on the number and types of problems that exist in their schools. This creates an incentive for principals not to have a gang problem. And like the parents, they don’t want to address it for what it is because of the stigma that goes along with it. Q. You’re telling people things they don’t want to hear. Is it frustrating to encounter such resistance and denial about what your research shows? Sometimes it is. When I was a police officer, I was frustrated with situations where you were showing people both qualitative

 Dr. M. Michaux Parker A native of Roxboro, N.C. Parker has been a member of the NCCU faculty since 2007. He earned a Bachelor of Science degree in criminal justice from NCCU in 1993 and began a career in law enforcement that included four years with the Durham Police Department, where he was a gang specialist and field training officer. He returned to NCCU to earn a Master of Science degree in criminal justice, followed by a Ph.D. in the same field at Michigan State University. His research has been published in the Journal of Gang Research, the American Journal of Criminal Justice, the International Journal of Finance and Management and other publications. He is a 2012 recipient of the Thrasher Award from the National Gang Crime Research Center for “superior service in gang prevention.”

and quantitative data that explained what they were dealing with — but they didn’t want to address it. All you can do as a researcher is produce the most rigorous research you can and present it in the best way possible. You can’t force anyone to address an issue. You can’t make people rear kids in a certain way or pay attention to the signs and symbols exhibited by their children. Likewise, you can’t force anyone to have a safer community. Q. Some school administrators are receptive, though. When they are, what can you do to work with them? For administrators who are interested, we have a wide range of tools and services. We can provide assessments to determine the incidence and prevalence of gang behavior in their schools and communities. We have standardized gang assessments, including one administered to individual children that uses composite measures to gauge

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characteristics associated with gang membership. We can actually assess mathematically not only whether kids are involved with gangs, but also how much they are at risk for becoming involved. For law enforcement agencies, we can do a tactical assessment. With this we can help them assess — again, mathematically — how many groups they have, what the sophistication levels are, and we can rank the groups in terms of the threat they present to the community. We can provide gang awareness training for school members, parents or teachers. We can also do trainthe-trainer situations for law enforcement, provide them with strategies that are effective for different types of gang-related crimes. If we can tear down the walls and the stigma that goes along with it, we can intervene. We also want to be a resource for smaller law enforcement agencies that don’t have money or resources for gang specialists. But


We can provide gang because they’re fighting that stigma, they’re sometimes reluctant to reach out for help. Q. What do you think should be done about gang problems here in Durham? What policies would you implement? If I had a magic wand, I would start with an assessment to determine the number of groups that are here, their level of sophistication and the level of crime they’re engaged in, so I could rank and classify each group to show how much of a threat they pose. Then I would undertake a systematic investigation of each group using the federal RICO (Racketeer-Influenced and Corrupt Organizations) law — not just one or two gangs, but all of them, to remove them from the city. That may seem like an extreme response, but the problem here is a lot more entrenched than people perceive it to be. Quite a bit of research shows that RICO prosecution is one of the most effective ways to actually remove gangs from a jurisdiction. It takes time and resources, and it requires collaboration between the local police and a federal prosecutor, but it allows you to take all the members of a gang rather than just a few people at the top who have others waiting to step up. It’s a lot like cancer. If you’re having surgery, the surgeon has to remove all of the cancer, because if he doesn’t, it’ll grow back, often in a more virulent way. Then I would allocate resources to Parks and Recreation to create structured programs year-round for kids. Research we’re seeing shows that a high number of kids are joining gangs simply because they don’t have anything else to do. Those issues can be pretty easily addressed by offering alternatives. From the recovery and intervention standpoint, I would allocate

awareness training for school members, parents or teachers. We can also do train-the-trainer situations for law enforcement, provide them with strategies that are effective for different types of gang-related crimes.

more resources to social service organizations. Many of the forces that steer kids toward gangs originate from need, and social service organizations are better able to address those things. Law enforcement agencies lack the mandate and funding to serve as social service providers. Under normal circumstances, law enforcement also lacks the authority to go to someone’s house and check on a child’s well-being. The point is, this is not simply a law-enforcement issue. We should be directing the appropriate resources to the appropriate agencies. Q. Do any communities actually have such a coordinated approach? Some communities may claim to, but few actually do; that’s a recurring problem within criminology. Law enforcement officers don’t want to be regarded as social workers. And social workers don’t like to act as police officers. They don’t work very well together on prevention. Q. In communities where gangs are established, the violence — particularly the shootings and homicides — seems to run in cycles. What factors influence this? There are many. You can have something as simple as gang members deciding to pursue a new criminal activity. This might reduce one type of crime while causing another type to spike. Gangs have evolved to where they don’t fight for turf the way they used to. They fight for criminal markets. If a gang is selling drugs in one particular area and they think

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another gang is trying to move in, you’ll have conflict. Another factor is how well the gang polices its own members. Having members who are excessively violent will attract attention from law enforcement, which is bad for business. A gang member who is a lone wolf can spike a crime wave simply because of the rules of gang culture. A new member who hasn’t really learned the rules of the gang — one who buys into the TV image that a gang member is supposed to shoot people and do drive-bys and crazy things like that — that one person can trigger violent policies of the gang. If the lone wolf shoots a rival gang member, the rival gang is required to shoot two or three of the first gang in retaliation, and so on. So the initiation of the wrong person into a gang can initiate a wave of violence. Another issue is urban development. It can change the crime dynamics of an area. For example, when they tore down Few Gardens in Durham some years ago, the residents — including the gang members — dispersed all over the city. So you can have many of these forces and changes — and we haven’t even mentioned law enforcement. Policing strategies, of course, can change the dynamics of crime in a community. These are things from a research standpoint we need to track. We should track the fluctuations to determine what correlates with what. It’s far too simple to say just one element contributes to an increase or decrease of any aspect of the crime rate.

Q. You say that gangs fight for markets much more than they fight for turf. So are they essentially business enterprises? If you are a leader of a gang that has evolved beyond the simple dynamics of just causing mayhem, violence is bad. According to movies and TV, all gang members want to do is commit violence all the time. In reality, gangs have to make money — with drugs especially, there are serious profits involved — and violence is bad for business. They resort to violence only when they perceive they have to. The more violence your gang is involved in, the more attention you draw from police. And you run the risk of making what we call the fatal error if you’re a gang leader: You don’t ever want to turn the community against you. In most areas where gangs are entrenched, the community supports them. They give money to people, they buy ice cream for kids, they buy toys at Christmas, they give food away — that’s what we call the corporatization of gangs. You see this all over the country, and you certainly see it in parts of Durham. Gang members in a specific neighborhood take care of people, even though they are selling drugs and are engaged in all sorts of crime. But if there’s too much violence for too long, you run the risk of falling out of favor with the community. And the neighbors will then rat you out, where they wouldn’t have told on you before if the violence was moderate.

Citizens don’t fully appreciate how organized and sophisticated gangs are. They don’t just stand here and wait for a new criminal interventions to stop them. Because they’re at risk of going to prison for the rest of their lives, gang leaders and members are actively combatting your gang intervention. They’re not static. They adapt. And they adapt more quickly than we do because they have to. Q. You’re working toward building a model — a set of tests and questions and assessments — that has the potential to identify kids who are most at risk for gang involvement and intervene. That’s a kind of ultimate goal, right? Yes. One goal is to further develop a mathematical assessment to let us know not only whether or not specific children are at risk of becoming gang members, but telling us mathematically how close they are to that gang membership. We call it a Gang Risk Assessment Model (GRAM). The GRAM assessment looks at their level of defiant individualism, which is a personality trait highly correlated with gang membership; their association with deviant peers, on a scale; their association with gang members; their level of school engagement; their level of emotional intelligence, and their level of parental involvement. All these things have been shown to correlate with gang membership. So we take these different components and we mathematically test to see if there’s a statistically significant

difference in the amount of each of these characteristics between the target group — the possible at-risk group — and actual gang members. This type of analysis is much more rigorous than just saying he or she is wearing red, or wearing blue; we call those types of identifiers artifactural identifiers, and they’re not very good. It’s too easy to misidentify someone. But using this mathematical model, we’re able to look at personality differences, associative differences, engagement differences, things that aren’t going to change overnight, things that are more accurate indicators of what that kid is actually thinking, believing and going through. And that would let us target kids more quickly — and much more accurately. Q. You say that gangs are everywhere, but most of the research still seems to focus on the big cities. Why? That’s a problem. Researchers tend to skew the research toward urban areas. You’re much more likely to get funding for a study that fits preconceived ideas. A gang study focused on inner-city Detroit or Chicago is more likely to be funded than one located in Beverly Hills. That doesn’t mean there are no gangs there, but it goes back to the stigma. Beverly Hills doesn’t fit the stereotype. Challenging preconceived ideas about gangs all but guarantees the research won’t be well-received. Q

a m g i st e. e h t en d v n r a inte s l al can w e h t, we t n crime scene cr dow with i a rim ge scene cr e n t o n ime scen l a es a c e If what go t 19

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a u x e S a g n i l k c Ta

d e tt i m s n a r T y ll

by Marla Vacek Broadfoot

The gonorrhea bacteria has developed resistance to antibiotics; Daniel Williams is exploring new lines of attack.

An alarming development has occurred in the evolution of the sexually transmitted disease known as gonorrhea or, in slang, “the clap.” Once easily treated with penicillin and other antibiotics, the disease has mutated into a “superbug” that is impervious to all forms of antibiotic treatment. Scientists around the world have increased efforts to develop alternative forms of therapy and to

understand the process by which Neisseria gonorrhoeae becomes resistant.

One scientist who entered the field years ago is Daniel Williams, Ph.D.,

associate professor of biology at North Carolina Central University. Williams has been uncovering the many strategies that the N. gonorrhoeae bug employs to thwart treatment. The work can be trying and difficult, but he is undeterred.

“I've had many struggles in my life, so frustration for me is a little bit

different than for most people,” Williams says. “I get frustrated — I'm not saying I don't, but my tolerance is probably a lot better than some people. I'm going to find a way to do what I need to do. That's just me, point blank. That's my personality.”

Illustration by Tiffany DaVanzo Photos by Ted Richardson

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A Rough Start

Williams spent his formative years in the foster care system, from childhood until he landed a track scholarship to NCCU. Growing up on a farm, he worked hard as a young boy by harvesting tobacco, wheat and corn and learning to lay bricks. While his body was engaged in manual labor, Williams’ mind was engaged in the details of his surroundings — noticing the ponds and creeks and wondering what kind of life existed in them. “I’ve always been interested in figuring out how things work,” says Williams, who might still be laying brick if his high school masonry teacher hadn’t urged him to go to college. As an undergrad, Williams became more and more interested in science, but he still wasn’t sure if he wanted to do it for the rest of his life. So tested the waters by going for his master’s in biology. That trial morphed into a career, as Williams went on to a Ph.D. at N.C. State and then a postdoctoral fellowship at Emory University. It was there that he became intrigued by the topic of antibiotic resistance in bacteria. The mechanism of antibiotic resistance that Williams studied as a postdoc involved drug efflux pumps, tiny chemical mechanisms found in bacterial membranes that can recognize a broad range of antibiotics and pump them back out of the cell. But the gonorrhea bacteria has many additional ways of developing resistance to antibiotics. It can produce certain enzymes that render a drug ineffective. It can make changes in its own DNA called target-site modifications that mask the site on the microbe where the drug is supposed to attack. In fact, it seems like it can make any number of changes to its underlying DNA — through approaches called chromosomal-mediated resistance or plasmid-mediated resistance — to evade therapies. Recently, the World Health Organization issued a warning that gonorrhea has become so crafty that it may soon become untreatable. If left untreated, gonorrhea can spread to other organs, causing infertility, pelvic inflammatory disease, tubal pregnancy and damage to the joints and heart. “Eventually gonorrhea triggers an inflammatory response, causing tissue damage that gives the infection access to more nutrient-rich environments and allows it to spread throughout the bloodstream. The idea is to stop it before it gets to that point,” Williams says.

Microbial Resistance

Williams’ research identifies weaknesses in N. gonorrhoeae’s arsenal of resistance that others may be able to exploit in developing new therapies for the disease. His first studies upon joining the NCCU faculty in 2005 focused on

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Daniel williams

Associate Professor of Biology

the point of contact between the bacteria and the host cell. This contact — the initial step of infection — is made by little appendages on the bacterial surface called type IV pili. Williams has gone on to study how these structures work at the molecular level. He has also focused on another likely target of new drugs, the cell wall. Williams has discovered a molecule that coordinates a large-scale recycling effort to rescue and reuse pieces of the cell wall as the bacteria multiply and divide within the host. In the process, this master molecule appears to trigger the release of chemicals called cytotoxins, which then cause different types of inflammatory responses in the host — causing gonorrhea’s most severe complications. “That is where my research is heading, to look at what is happening from the perspective of the host cell,” Williams says. “How is the host cell responding to the infection, and can that response be tweaked to control the inflammation and its effects?”

Widening the Scope

Right now, Williams’ lab solely uses in vitro methods — meaning it looks at how the microbe acts in a test tube. He is reaching out to some of his mentors and colleagues — William Shaffer at Emory, Robert Nicholas at UNC–Chapel Hill and Antonio Baines at NCCU — to explore how the microbe behaves in cultured mammalian cells. “Even if I only contribute to the textbook knowledge on how gonorrhea works, for me that is just as important as

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“Even if I only contribute to the textbook knowledge on how gonorrhea works, for me that is just as important as the possible medical implications. But if along the way I find something that can improve medical care, that’s even better.”


Advocating for Young Black Readers Daniel Williams, left, and biology graduate student Ronald McMillan discuss their research in Williams' NCCU lab.

Wendy Rountree seeks a higher profile for African-American literature for children and teens.

the possible medical implications,” Williams says. “But if along the way I find something that can improve medical care, that’s even better.” Williams is happy to be doing research back at his old alma mater. “One reason I entertained coming back here was that NCCU had this new science building and research facilities, and I really wanted to be able to change the perception that you can’t do good research when you come from a traditional liberal arts college,” he says. “I looked at it as an opportunity to come in at the ground floor and give students the chance to do research on campus.” He has already raised NCCU’s profile as a research center. In 2009, he was elected president of North Carolina’s branch of the American Society for Microbiology. He was the first African-American male to hold that office, and his election gave NCCU the distinction of being the first historically black college or university to host the group’s annual meeting. For Williams, raising the stature of NCCU goes hand in hand with his day-to-day work studying STDs. When he succeeds in one arena, it ultimately influences the other. “Progress can be slow, but to me this is not hard work,” he says. “I’ve experienced hard work. I just try not to get frustrated, and believe that somehow I’ll figure it out.” Q

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hen she was little, Wendy Rountree, Ph.D., loved reading the books of iconic authors Judy Blume and Beverly Cleary. But as she grew older, she realized their stories of childhood angst, friendship and identity didn’t completely resonate with her own experiences. “I started wondering where the characters were that looked like me,” says Rountree, now an associate professor of English and Mass Communication at NCCU. “I couldn’t find them. In fact, it wasn’t until I started doing research as a graduate student that I began to uncover those stories that I had been craving. They existed – just not in the schools.” Rountree built a chapter of her dissertation around the topic, eventually finding enough suitable characters to fill up a book of her own, called “Just Us Girls: The Contemporary African-American Young Adult Novel.” The 2008 book critically reviewed major themes of novels written primarily for adolescent African-American girls, such as the importance of beauty and the silencing of young women’s voices. More recently, Rountree turned her literary acumen to novels for African-American boys. Published last year, “The Boys Club: Male Protagonists in Contemporary African-American Young Adult Literature,” explored what it means to be young, black and male in America today.

A Demographic at Risk Why focus on boys? Scientific studies, higher education indicators and media reports all indicate that AfricanAmerican boys are in serious jeopardy. They are more likely than any other group to be suspended or expelled from school. They are less likely to graduate from high school, and more likely to be the victim or perpetrator of a homicide. All of these factors add up, making African-American males the only demographic group whose life expectancy is actually declining. “The educational system is taking a hard look at how to better engage this high-risk group in the classroom, not only in higher education but in the K 12 curriculum,” Rountree says. “I think reading is a great way to interest and inspire our youth, but only if they can see themselves in the stories.” In her book, Rountree explores issues of education, as well as violence, identity and racism. For example, she looks at the notion of manhood as violence in a number of novels, including Sharon Flake’s “Bang!” When one of his sons dies from a gunshot wound, a father responds by inflecting a cruel African ritual on his other child in an

effort to keep him from being “soft.” He casts his son out of his house to live on his own, and though there is a reconciliation of sorts in the end, his actions have horrible consequences. “I wondered what in the world is the writer trying to convey here?” Rountree says. “It may be that in the wrong 26

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hands, cultural knowledge can be misused. That can be something that's very difficult to think about, but by putting his son in this ritual, he actually forces him into a life of violence. The son has to almost claw his way back to his humanity. It was a fascinating story, and one of the very harshest depictions I've read of how violence can impact an individual.” Rountree analyzes works by other well-known and up-and-coming writers, including Kenji Jasper, Jacqueline Woodson, Candy Dawson Boyd, William McDaniels and Walter Dean Myers. Rountree personally interviewed two of the writers, Kekla Magoon and Christopher Paul Curtis, to learn the motivation behind their novels. She found that they, like many of their counterparts, feel a duty to write for this particular audience. Novels with African-American protagonists, as Rountree writes in her introduction, can capture the interest of AfricanAmerican boys and guide them through many of life’s difficulties and problems — such as seeking academic excellence despite peer pressure to do otherwise. “Literature written for AfricanAmerican children is not necessarily art

for art's sake,” she explains. “These books are often meant to have some type of purpose. They can be to entertain, but they are also to inform, to fill in the holes in the history books so the other side of the story gets told.” For instance, Christopher Paul Curtis’s award-winning “Bud, Not Buddy” tells the story of a boy who is forced into the foster care system after his mother dies. Alone and unhappy, the boy fantasizes that the image of a jazz musician he finds on an old flier in his suitcase is actually his father. The book follows his journey to find the musician, who ends up being not his father, but his grandfather. Along the way, the reader learns about life in Flint, Mich., during the Great Depression, the setting of the novel. Rountree says this genre of historical fiction is popular with AfricanAmerican authors because it allows them to teach younger readers about the events of past while also engaging them with characters that don’t seem too different from themselves. One of her favorite examples is “The Rock and the River,” a debut novel by Kekla Magoon that describes the coming of age of two brothers alongside the civil rights and black power movements in 1960s Chicago. “Magoon did a wonderful job of encapsulating these two different movements within the context of a family,” Rountree says. “You see the fissures. You see the friction. You see that the two movements are basically trying to do the same thing, but with different approaches. And that neither is as cookie-cutter as the history books might indicate.” One topic that has been actively debated in African-American literature circles is the role of the writer. Rountree says that most of her peers feel that writers have a certain duty to leave their read-

ers with something tangible. The trick is entertaining the audience along the way so readers don’t feel like they’re being beaten over the head with themes and political points. “Writers are artists, and as artists you are faced with choices,” Rountree says. “When a writer decides that a character is going to be African American instead of Asian American or Caucasian-American, that choice carries certain implications. The question is, ‘What are you trying to say?’ In some cases a writer could be using an African American character to say, ‘Hey—I’m just like everybody else.’ So you don't even necessarily have to talk about social, political issues because that might be the political statement in and of itself.”

Elevating the Genre

Throughout her research career, Rountree has been troubled to find so few works of literary criticism analyzing African-American children’s and young adult literature. She thinks that research in this area is important because it can raise the visibility of the writing, making it more accessible to future writers, educators and general citizens. “There are many steps in between a book being written and it making its way into the hands of young readers,” Rountree says. “And many African-American authors have difficulty getting published, getting considered for reading lists, getting reviewed by academics. I think it is

important that we as scholars study and analyze these writers because, like it or not, that is one of the ways that they are legitimized." Rountree has a personal interest in elevating the standing of African-American young adult literature. She wrote her first novel, “Lost Soul,” in part, she says, because she was unable to find a story that accurately depicted the issues of identity, blackness and bullying she dealt with as a youth. Since the book was published in 2003, Rountree has had several people ask her about a sequel. Now that she has spent years critically analyzing other authors, she believes she may be ready to apply what she has learned to that next novel. Maybe this time her main character will be a boy. “I think my academic research and my creative writing have enhanced each other,” Rountree says. “Now that I know the rich history of the genre, I feel like I have more responsibility when I do start writing again.” She also feels a responsibility to her students, many of whom are aspiring writers. Every time they send a manuscript or a poem her way, she tries to give them constructive criticism — and words of encouragement. “I hope that whether through my teaching, or my research, or my writing, that I am able to inspire my students to read more critically and even write themselves,” Rountree says. “I want to have a positive impact, any way I can.” Q

Literature written for African-American children is not necessarily art for art's sake, these books are often meant to have some type of purpose. They can be to entertain, but they are also to inform, to fill in the holes in the history books so the other side of the story gets told.” — wendy rountree 27

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Someday

in the not-so-distant future, walls will talk. T-shirts will charge mobile phones. Military tanks will become invisible. These feats aren’t from the realm of science fiction. Rather, they represent the efforts of researchers worldwide to create what are known as smart materials. Smart materials are essentially objects that can respond or adapt to changes in their environment, such as stress, temperature, light, or pH. In reality, many inanimate objects already react to such changes — ice cubes melt, metal rusts. What sets the products of materials scientists apart is that these changes happen by design. The objects are infused with intelligence, engineered to have memory and a sense of direction, to detect problems and correct them. “It's kind of like a play on words. Materials aren't supposed to be smart. They're just supposed to exist,” explains Darlene Taylor, Ph.D., assistant professor of chemistry at NCCU. “But the fact that we can redesign objects to respond in specific ways to our environment, that's what makes them smart. If you change the pH from acidic to basic, a material might drop some of the chemical bonds that tie it together. Similarly, if you change the wavelength of light that you hit a material with, it might open or close its chemical conformation to adapt its overall structure.”

How Can Materials Be Smart?

by Marla Vacek Broadfoot

Chemist Darlene Taylor’s molecular manipulations create objects with intelligence.

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Photos by Ted Richardson


 A paraphenylene-based material emits a violet blue color when irradiated with ultraviolet light. Taylor says this material has the ability to convert absorbed light into energy and could have potential application in solar cell devices.

in the body, it won't spread everywhere and cause side effects. Instead, it is directly localized where it can be most effective.” When Taylor mentioned her idea to Phyllis Leppert, M.D., Ph.D., head of the uterine fibroid center at Duke University, the two decided to combine their expertise to generate more effective treatments for the condition. Uterine fibroids are the most common gynecologic tumor in women of childbearing age, affecting nearly 40 percent of premenopausal females.

African-American women are three times more likely to get fibroids than other women and are more likely to experience symptoms such as heavy bleeding and lower back pain. Since 2008, Taylor has conducted research in this area as a fellow of the NIH’s BIRCWH (Building Interdisciplinary Research Careers in Women’s Health) program, under the mentorship of Leppert and other Duke researchers Donald McDonnell, Ph.D., and Eric Toone, Ph.D. Taylor’s creation is a liquid when it is

SMART MATERIALS

Smart materials: objects that can respond or adapt to changes in their environment. (for example: stress, temperature, light, or pH)

a way to treat uterine fibroids

The exciting part of smart materials, in Taylor’s view, is that they can be designed for practically any purpose imaginable. For example, Taylor is adapting materials with two completely different goals in mind: to create new classes of drugs and to develop organic solar cells. Many drugs look promising in the laboratory but fail when tested in real life, either because their effects are diluted by the bloodstream or are toxic to normal cells. Taylor is trying to solve this delivery problem by encapsulating drugs within a protective bubble of smart material so the drug is released only after it has reached its target. “It is similar to making Jell-O, which can go from a liquid to a solid or a solid to a liquid when you change the temperature,” she says. “Think of the drug as fruit. When you envelop it in Jell O, it is protected when you put it into the human body. If you physically deliver it to a specific place

SMART MATERIALS:

The Power of Jell-O

3

Body temp changes smart material from liquid to solid within fibroid.

1

4 Drug is mixed into smart material (LiquoGel) which is liquid at room temperature.

Smart material (LiquoGel) degrades, drug seeps out into fibroid.

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Smart material/drug mixture is injected into fibroid transvaginally or transabdominally with ultrasound guidance.

Drug shrinks fibroid without injuring nearby tissue. Only a small amount of drug enters circulation.

SMART MATERIALS already in use: Electrochromic: LCD displays

Photochromic: color change lenses

Thermochromic: contact thermometer

8 100 102 104 106 96 9

Illustration by Tiffany DaVanzo 31

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 Taylor is collaborating Dr. Phyllis Leppert of Duke University to develop more effective treatments for uterine fibroids, the most common gynecologic tumor in women of childbearing age. She has developed a smart material for delivering a drug to treat the condition directly to the tumor, minimizing side effects. The material is an injectable liquid at room temperature that solidifies once exposed to body temperature. After it reaches the tumor site, holes develop in the material’s protective shell as it degrades, and the drug then seeps out into the tumor.


Materials aren't supposed to be smart. They're just supposed to exist.

But the fact that we can redesign objects to respond in specific ways to our environment, that's what makes them smart.

— Darlene Taylor

Next Stop: The Sun

sitting in a syringe at room temperature. When it is injected into the bloodstream and is exposed to body temperature, it becomes a solid. Once it has had time to reach the tumor site, holes develop in the material’s protective shell as it degrades, and the drug then seeps out into the tumor. But Taylor’s design doesn’t stop there. She placed an additional “handle” on the structure of her smart material, creating a landing spot for additional modifications like imaging agents or homing signals. “We can't predict all the possible uses, so this material is designed to do more,” Taylor says. “If I wanted to follow the compound with imaging techniques, I could put a dye or a tag on it and see where it's going as it degrades and circulates the drug, and track how the tumor reacts. Or let’s say I wanted to go beyond uterine fibroids and use the material to treat breast cancer. With all these additional handles I have another way I can tweak it, so it not only responds to temperature, but also targets other types of tumors or becomes more sensitive to radiation. There are a number of reasons, both scientifically and medically, that you want to have these additional handles on there.” Taylor has partnered with industry to see if her smart material can resurrect promising drugs that weren’t able to pass clinical trials. She and Leppert are first testing their new versions of these drugs in tissues taken from patients who have undergone hysterectomies. If they are successful, the next step will be to determine if the new drugs can shrink uterine fibroids when administered directly to patients.

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“I like to know that what I'm doing is going to have an impact,” Taylor says. “For me, it isn’t compelling to be a scientist simply for science's sake. Even though I'm still working at this very basic level, I want to feel like somewhere down the road my work could turn into a real and meaningful application.” One application that she is working toward involves photovoltaic devices, commonly known as solar cells. Solar energy may seem like a far cry from drug delivery, but to Taylor the common bond is new and improved materials science. Right now, she is developing materials that can act as a smart surface to harness sunlight and convert it to electricity. The approach mimics what plants do naturally: use their leaves to catch light, which they convert to sugar that can fuel their growth and development. Taylor’s “polymer antennas,” as she calls them, also capture and manipulate the hopping of electrons from the sun’s rays to do work, like power a car or heat a house. Her research is part of a larger effort within the Solar Energy Research Center at UNC-Chapel Hill, where she is an adjunct professor. The center, which involves collaborations between like-minded scientists at NCCU, Duke, N.C. State and the University of Florida, is funded by a $17.5 million grant from the U.S. Department of Energy and President Barack Obama’s American Recovery and Reinvestment Act. Taylor is a member of the “polymer” group that meets weekly to discuss the center’s progress toward creating materials for artificial photosynthesis and the production of solar fuels. Polymers are large molecules composed of repeating structural units; they form the basis of most smart materials. Taylor says once you where to look, you will find polymers nearly everywhere. “I can't think of any of today’s technologies that would have been possible had it not been for polymers,” Taylor says. “Cell phones are made up of polymers. Lightweight clothes that can cool the body even when you’re sweating, those are made of polymers. Solar cell devices can be made of polymers. Instead of using inorganic, unattractive solar sheets, just imagine being able to paint an organic, woven solar membrane onto the side your house to capture sunlight. Polymers will make all that possible. I guess you can say they’re the future.” Q

Cutting Off Cancer’s Communication Lines

Antonio Baines Looks for Ways to Disrupt a Killer’s Biochemical Processes ............................................................................................................... Written by Marla Vacek Broadfoot / Photos by Ted Richardson


C  Working under a biosafety hood in the Mary M. Townes Science Center, Antonio Baines pipettes a solution into a tissue culture plate.

ancer is scary in

any form, but pancreatic cancer is positively terrifying. Occurring in an organ deep within the abdomen, pancreatic tumors can develop and even spread before producing recognizable symptoms. The lethal malignancy is much more common among African-Americans, who are often diagnosed with an advanced, inoperable, form of the cancer. Regardless of race, most patients are dead within a year of diagnosis. One person who has witnessed firsthand how powerless the disease can render both patients and physicians is Antonio T. Baines, Ph.D., assistant professor of biology at NCCU. While Baines was doing his doctoral thesis work at the Arizona Cancer Center, one of the directors of the center developed pancreatic cancer. Although the director

had all the best resources and expertise at his disposal, Baines still watched him ultimately succumb to the disease. When a new director, a pancreatic cancer researcher himself, came on board, he encouraged Baines to go into the field. “I began to realize I could help cancer patients indirectly by conducting research in the laboratory,” said Baines. “I love basic research, but for me that basic research has to be translatable to the patient as much as possible.”

A Tangled Web

Over the past few decades, insights gained from basic researchers such as Baines have dramatically improved the early detection and survival rates for many types of cancers. By understanding how good cells go bad, scientists have helped generate earlier diagnoses, more effective surgeries and smarter therapeutics. Despite this significant progress, however, the outlook

remains dismal for major killers like lung, brain and pancreatic cancer. “There are still a lot of cancers that we don’t have a good handle on,” said Baines. “That lack of knowledge definitely presents a challenge. But it also means there is a lot of room for improvement, and that we have an opportunity to make a big difference for patients with pancreatic cancer.” On the door to Baines’ office in the Mary M. Townes Science Building hangs a life-sized poster that illustrates the complexity of his task. To the untrained eye, the poster looks like a multicolor array of arrows, bubbles and cryptic acronyms like NF-kB and p38. But to Baines, it amounts to a to-do list that details an entire cascade of molecular events that he and others can target in the fight against cancer. Those molecular events are the work of an intricate network of genes responsible for signaling cells to multiply when the body needs them, and to die before they grow out of control. If defects accumulate in too many of these genes controlling cellular growth and death,

cells become cancerous. At the top of Baines’ poster is the gene most likely to go awry in pancreatic cancer. Mutations in this gene — called K-Ras — are found in 30 percent of all human cancers, and 90 percent of all pancreatic cancers. Baines first became familiar with K-Ras as a postdoctoral fellow in Dr. Channing Der’s lab at UNC-Chapel Hill. There, he studied how mutations in K-Ras can signal other molecular partners within the cell to act inappropriately, perhaps by accelerating cell division or causing cells to forget to die. After years of work, Baines helped to discover

a critical step in the transformation of normal pancreatic cells into cancer. The finding, which appeared in the high-impact journal Cancer Cell, gave the field a novel molecular target for developing a drug to treat pancreatic cancer.

A New Target

Researchers have made a concerted effort over the last three decades to create a cancer drug that directly blocks K-Ras. But because this gene acts as an on-off switch for many normal functions within the cell, these attempts have proved ineffective or too toxic to take into the clinic. Therefore, scientists like Baines have decided to take another approach, targeting cancer by taking out K-Ras’s cellular partners. Baines’ first challenge as an independent researcher was deciding which of the hundreds of possible targets to go after first. Reading up on the scientific literature, Baines found a genetics study that compared cells from a normal pancreas with those in which K-Ras had been mutated experimentally. The paper showed that a whole bunch of genes

If you want to see if a gene would make a good drug target, you have to show that there is more of it in the tumor versus the normal, which we did. It meant we were on the right track.” — Antonio Baynes

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were “turned on” or “turned off ” in cells with the mutant K-Ras, compared with the normal cells, as would be expected during the development of cancer. Among those “turned on” by K-Ras activation was a family of genes called PIM kinases. These genes, like K-Ras, are considered oncogenes — molecular entities that can cause cancer by helping cells grow uncontrollably. With further digging, Baines came across another paper showing that the first of the three members of this Pim kinase family, namely, Pim-1, was present at

abnormally high levels in samples from pancreatic cancer patients. He knew he had found his target. Before Baines could start going after Pim-1, he had to make sure that the previous findings pointing to its role in pancreatic cancer were all true. First, he used an advanced molecular technique called RNA interference that chops up K-Ras’ genetic message in the cell. When he watched to see how the loss of K-Ras affected the Pim kinases, he found that the activity of Pim-1, but not Pim-2 or Pim-3, went down. He then went on to confirm that there were indeed differences in this gene between normal and cancerous pancreas cells. “If you want to see if a gene would make a good drug target, you have to show that there is more of it in the tumor versus the normal, which we did,” said Baines, who has a joint appointment in the cancer research program at NCCU’s Julius L. Chambers Biomedical/Biotechnology Research Institute. “It meant we were on the right track.” If there are abnormal amounts of Pim-1 in pancreatic cancer, it follows that knocking out its activity could be a way to treat the disease. So Baines used his RNA interference technique again, this time targeting Pim-1 for destruction in the cell. He found that the loss of Pim-1 impacted crucial aspects of cancer development by reducing growth, decreasing invasion into neighboring tissue, and making cells more sensitive to radiation therapy.

The Way Forward

Baines is now collaborating with a number of pharmaceutical companies that have Pim kinase inhibitors in their pipeline to see if the drugs can stymie cancer

Disarming a time bomb

Pancreatic cancer is among the most lethal of cancers — the cause of one out of every four cancer deaths in the U.S., and difficult to detect until it has advanced and spread. Cancer is caused by sequences of chemical reactions known as signal transduction pathways, involving numerous proteins within cells. Researchers have known for decades that a key player in pancreatic cancer is a protein called K-Ras that controls cell growth. Normally, K-Ras works like a switch, turning on when growth is needed, and then shutting off, but a mutated form of the protein stays turned on, causing the uncontrolled growth and cell division that can lead to malignant cancer. Mutated K-Ras is present in 90 percent of all pancreatic cancers, but efforts to target it directly with drugs have not been successful. Researchers now seek to disrupt mutated K-Ras signaling indirectly by targeting proteins influenced by K-Ras activation. Antonio Baines has identified a target in a protein known as Pim-1, one of a family of proteins called Pim kinases. His research suggests that inhibiting Pim-1 holds promise as a way of disrupting the mutated K-Ras signaling, and thus disrupting the growth of pancreatic tumors. He is working with drug companies to see if a treatment can result from this research. 37

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Mary M. Townes Science Complex

Julius L. Chambers Biomedical/Biotechnical Research Institute (BBRI)

For more information about research at NCCU vist www.nccu.edu or call 919-530-6893

 The lab notebook of Naima A. Stennett, a graduate student working with Baines, contains calculations to determine the protein concentrations of various tissues.

growth. So far, the results are promising enough that Baines and one of his pharmaceutical partners presented a collaborative poster at the annual meeting of the American Association for Cancer Research in April in Chicago. “Industry has a huge role to play in translating research findings,” said Baines. “I don’t need to personally make a drug — I am more interested in doing the basic science to validate possible drug targets. If I can add to the body of knowledge that may one day lead to better treatments for pancreatic cancer, then that is enough for me.” That hope of making a difference for patients with the lethal malignancy is one thing that gets Baines up in the morning. Another is the opportunity to get his students interested in the sciences. Baines is happy to share the credit for his accomplishments with the undergrads, graduate students, technicians and who that work in his lab. “I think the increase in research infrastructure at this university over the past five years has helped to create better opportunities for both faculty and students,” said Baines. “Two of my past research students are at Harvard Medical School — one in medical school and the other in a combined MD/Ph.D. program — and I think because of their experience here they want to include research as part of their career moving forward.” If Baines isn’t able to see a cure for pancreatic cancer in his lifetime, perhaps one of his students will. Q

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Biomanufacturing Research Institute & Technology Enterprise (BRITE) Photos ©JWest Productions


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Quest Winter 2013