Research Fall 2015

AUGUSTA UNIVERSITY

COLIN’S JOURNEY Cancer Patient’s Treatment Paves Way for Other Children

FALL 2015

VOL. 3

NO. 2

DISCOVERIES

IN

PROGRESS

CONTENTS Research magazine is produced twice a year by the Office of the Vice President for Research, in conjunction with the Division of Communications and Marketing.

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PRESIDENT Dr. Brooks Keel

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PROVOST Dr. Gretchen Caughman SR. VP FOR RESEARCH Dr. Michael P. Diamond VP FOR COMMUNICATIONS AND MARKETING Jack Evans

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EDITOR/WRITER Christine Hurley Deriso

SENIOR PHOTOGRAPHER Phil Jones

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©2015 AUGUSTA UNIVERSITY

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COLIN’S JOURNEY Cancer Patient’s Treatment Paves Way for Other Children

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A SCIENTIST AT HEART

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GROWING PAINS

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GETTING THE LEAD OUT

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THE LAW OF THE LAND

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‘WHOA DEATH’

ASSISTANT EDITOR John Jenkins ART DIRECTOR Tricia Perea

AT A GLANCE

New President Draws on Lessons Learned in Augusta University Lab

University Builds on Pioneering Role in Reproductive Endocrinology

Research Spurs Advances in Imaging Technology

Nationwide Headlines Inform Perceptions at Local Level

Historian’s Look at Folk Religion Unearths Fighting Spirit

Dear Readers, ONE THING that strikes me about this edition of Research is how beautifully it highlights the variety and diversity of our funding sources – and how quickly small gestures can add up.

Our university, which has recently been renamed Augusta University, receives an impressive amount of funding from the National Institutes of Health, the most competitive and eagerly sought of all U.S. biomedical research funding sources. Last year, for instance, our research awards were up nearly 18 percent over the previous year, and nearly half of our 800 proposals were submitted to the NIH. But even though the NIH is the behemoth of funding sources, the articles in this edition of the magazine demonstrate that a little creativity and generosity can move mountains.

Consider the cover story, for instance, on pediatric oncology research. An Augusta University discovery of the role that an enzyme called IDO plays in protecting a fetus from the mother’s immune system has unleashed incredible biomedical breakthroughs, including Dr. Theodore Johnson’s clinical trials of a new treatment for brain cancer.

His funding sources include foundations started by families whose children battled cancer. Their selflessness in the face of their own struggles is truly incredible, and their foundations hold the promise of new hope for countless other pediatric cancer patients. One of those patients, Colin Hayward Toland, is featured in the article. We hope you find this charming little boy’s story as moving and inspirational as we do.

Another creative funding source is our own Center for Undergraduate Research and Scholarship Program. The program incentivizes undergraduate participation in faculty research projects, and the results can be amazing. Consider, for example, our undergraduates’ contributions to research shedding light on perceptions toward law enforcement officers and research spurring a giant leap forward in imaging technology. Both are featured in this edition of the magazine.

Says Abigail Drescher, coordinator of the program, “Undergraduate research enables students to engage with faculty outside of the classroom and enhances their ability to apply knowledge from the classroom to issues in their discipline.”

But the true beneficiaries are the members of society whose lives will be improved by the center’s research findings. We are extremely proud to host such an innovative program.

Thank you for letting us share our stories. n

Dr. Michael P. Diamond SENIOR VICE PRESIDENT FOR RESEARCH

AT A GLANCE GROWING FOOTPRINT THE CANCER RESEARCH building at Augusta University is getting a larger footprint and a new name.

The 170,000-square-foot facility on the corner of Laney Walker and R.A. Dent boulevards will gain 72,000 square feet of new space and undergo 6,000 square feet of renovations to become the M. Bert Storey Research Building, in recognition of the Augusta philanthropist and longtime university supporter.

“This $62.5 million project will be a significant expansion for the Cancer Center that will physically connect our clinical and research missions as we continue the momentum toward

National Cancer Institute designation,” said Augusta University President Brooks Keel. “We couldn’t make this happen without the generosity of supporters like M. Bert Storey, who understand the impact that our discoveries make in the fight against cancer.”

The state of Georgia is providing $50 million in bond funding, and the university is securing the remaining funds to finance a five-story expansion to the existing research building and an elevated connector linking the building to Cancer Center Outpatient Services.

The naming was approved by the University System of Georgia Board of Regents on Aug. 12.

“It is my honor to lend my name to such a worthy endeavor,” said Storey, president and owner of Bert Storey Associates LLC, a commercial real estate development company, and chairman of the Storey Foundation. Storey also helped raise funds for Augusta’s Kroc Center and serves as an Augusta University fundraising campaign cabinet member. He and son Barry received the 2010 Outstanding Philanthropist Award from the Greater Augusta Chapter of the Association of Fundraising Professionals.

For more information about Augusta University’s cancer initiative, visit gru. edu/cancer. n

CANCER CONTROL

DRS. MUTHUSAMY THANGARAJU AND RAJNEESH PATHANIA

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M. BERT STOREY

THE GENE AND HORMONE soup that enables women to breastfeed can be a recipe for breast cancer, particularly when the first pregnancy is after age 30.

Researchers have found that the gene DNMT1 is not only essential in maintaining stem cells that enable normal rapid breast growth during pregnancy, but that the gene is highly expressed in the most common types of breast cancer.

Conversely, ISL1 gene, a tumor suppressor and natural control mechanism for stem cells, is nearly silent in the breasts during pregnancy as well as cancer, said Dr. Muthusamy Thangaraju, an MCG biochemist and corresponding author of the study in the journal Nature Communications.

“DNMT1 directly regulates ISL1,” Thangaraju said. “If the DNMT1 expression is high, this ISL1

Research Fall 2015

gene is low.” They first made the connection when they eliminated DNMT1 in a mouse and noted the increase in ISL1. Then they got busy looking at what happened in human breast cancer cells.

They found that restoring higher levels of ISL1 to human breast cancer cells dramatically reduces stem cells and the resulting cell growth and spread that are hallmarks of cancer. The finding points toward new therapeutic targets for breast cancer and potentially using blood levels of ISL1 to diagnose early breast cancer.

In fact, the researchers have found that the anti-seizure medication valproic acid, already used with chemotherapy to treat breast cancer, appears to increase ISL1 expression. The scientists are screening other small molecules that might work as well or better. n

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AT A GLANCE

DRS. CHUNHONH YAN AND HONGMEI CUI

CELL STRESS REPAIR DNA DAMAGE INCREASES the risk of cancer, and researchers have found that a protein that assists stressed cells plays a critical step in its repair.

ATF3, or activating transcription factor 3, appears to increase its levels in the face of cell stress, then bind to another protein, Tip60, to attract a swarm of other proteins to the damage site.

“When a cell senses stress, such as DNA damage, this protein can be induced,” said Dr. Chunhong Yan, an MCG molecular biologist and corresponding author of the study published in the journal Nature Communications. “One of the things we found is that ATF3 can bind to the Tip60 protein and promote the DNA damage repair function.”

Like Tip60, ATF3 is expressed at low levels until cells get stressed, and DNA mutation is one of the most common cell stressors. ATF3 then finds and binds to Tip60, increasing the usually unstable protein’s stability and level

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of expression. “If you look at the DNA under the microscope, you will see the damage site somehow labeled by this protein,” Yan said.

Tip60, in turn, modifies the protein ATM, helping it form a sort of scaffold where other workerbee proteins soon assemble.

While it may take years for a cell to recognize DNA damage, once it does, the response occurs within minutes. One of the early arrivals to the ATM scaffold is p53, a powerful tumor suppressor. Once on the scene, p53 helps assess whether the damage is reparable. If not, it triggers cell suicide. If the damage is fixable, it will arrest cell proliferation and help start the repair.

In human cancer cells, the researchers have shown that ATF3’s role precedes previously known steps. Future studies include finding a drug that could help cells make even more of this stress responder as a possible adjunct cancer therapy. The research was funded by the National Institutes of Health. Dr. Hongmei Cui, a postdoctoral fellow, is the study’s first author. n

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FIRE IN THE BELLY

CYBERSECURITY BOOST

Augusta University is among 15 institutions in the nation to receive federal funding to help train the next generation of physicianscientists in obstetrics and gynecology.

Augusta University has launched the Cyber Institute to develop research, new curricula and outreach opportunities in cybersecurity.

The university will receive $1.7 million over the next five years from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development to train obstetrician-gynecologists to also become independent investigators in women’s health fields.

“We want individuals with fire in their belly to be able to get involved in research,” said Dr. Michael P. Diamond, chairman of the Medical College of Georgia Department of Obstetrics and Gynecology, Augusta University senior vice president for research and principal investigator for the new program in Augusta. “It’s a great opportunity to train clinicians to be clinical investigators.”

The program is available for junior faculty as well as residents and fellows who have completed training at locations across the nation or at MCG. The program funds two positions at a time for a maximum of five years in Augusta. Federal dollars will help support the salaries and the research of the program scholars.

“We want to be known for cyber,” said Joanne Sexton, director for Augusta University Cyber Security Educational Initiatives. “The Augusta area has been growing in this aspect, and we want to be a major player in that.”

The Cyber Institute has already established a cyber curriculum, said Dr. Gretchen Caughman, executive vice president for academic affairs and provost, complementing nearby Fort Gordon’s new role as headquarters for the U.S. Army Cyber Command.

“We have made cybersecurity a major strategic priority,” Caughman said, citing funding from the University System of Georgia. The institute also advances the goal of recognition as a Department of Homeland Security and National Security Agency National Center of Academic Excellence in Information Assurance/Cyber Defense.

The institute will provide the framework for all things cyber at the university, in cooperation with several of Augusta University’s colleges, which offer cybersecurity courses and degrees. n

Having committed time for research is difficult for physicians, particularly more junior physicians trying to juggle building a practice and a solid research program, Diamond said. The federal grant enables the physicians to focus on research at least 30 hours weekly.

Dr. Nita J. Maihle, associate director of education for the Cancer Center, is the program director. Dr. Ayman Al-Hendy is the director of recruitment and Dr. Lara Stepleman is the director of evaluation. n

Research Fall 2015

JOANNE SEXTON

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COLIN’S JOURNEY Cancer Patient’s Treatment Paves Way for Other Children

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Colin Hayward Toland has a tried-and-true method of making friends on a plane.

Once buckled into his seat, he’ll take the paper and pencil provided by his mother,

write “Hi, my name is Colin. What’s yours?” and hand it to the passenger behind him.

The paper invariably gets passed back, often posing follow-up questions. A new penpal occasionally asks Colin, for instance, where he’s headed. He writes back, “To see Dr. Johnson,” charmingly inverting the J. This pastime is so typical of Colin’s sunny personality that his bemused mom has to remind herself how improbable it is.

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‘He Looked Scared’

Colin, now 8, was diagnosed at age 2 with ependymoma, a malignant brain cancer. “He started stumbling a lot,” says his mother, Tamiko Toland, of the symptoms that led to his diagnosis. “Then he woke up on a Sunday morning – the day we’d scheduled a pool party for his second birthday – and his legs didn’t work at all. I was holding him and his back arched. He was stiff. He just looked very scared.”

A brain scan confirmed the crushing diagnosis. Toland, a writer from Ithaca, New York, absorbed the news with characteristic stoicism. She didn’t have time for self-pity; it was time to formulate a game plan. And that’s just what she and her husband, Ian Hayward, did.

Two surgeries followed, including one in 2009 that damaged the nerves on the right side of Colin’s brain stem, leaving him unable to talk, walk or swallow. The family, which includes son Aidan, age 11, eventually ended up at St. Jude Children’s Research Hospital in Memphis.

“After two surgeries, we still had residual tumor, so we needed a path to remove it,” Toland says. “St. Jude offered that through chemo. We opted for an experimental protocol because, without complete removal of the tumor, there’s little chance of a cure.

Aggressive treatment was our only option.” But despite the risks, the treatment gave Colin the hope of a future. After another surgery, chemotherapy and radiation, the cancer was in remission.

Colin squandered not a single minute in making up for lost time. With extensive physical, speech and occupational therapies combined with the incredible resilience of a toddler committed to reclaiming his life, he regained nearly all of the function he lost.

The ensuing five years were incredibly fulfilling, with the family rediscovering the rhythms of a normal, happy life. Colin thrived in school; brother Aidan excelled in soccer. Life was good.

But Colin relapsed last January.

Doing Some Good

At this point, his parents hoped for a second chance through radiation to the whole brain and spine. But they were looking to delay the treatment, with its significant long-term side

effects. With no other standard treatment options on the table, they were willing to consider anything that turned the odds in his favor. Enter Dr. Theodore Johnson, the one whose name Colin spells with a backward J. It was during his Medical College of Georgia MD/PhD education that Johnson, now an assistant professor of pediatrics at his alma mater, began studying an enzyme called indoleamine 2,3-dioxygenase (IDO) with Dr. Andrew Mellor, director of the Cancer Research Center. In the 1990s, Mellor and his colleague, Dr. David Munn, discovered the role of IDO in protecting a fetus from the mother’s immune system during pregnancy.

The groundbreaking finding unleashed a flood of other potential implications made possible by the understanding of how to manipulate the immune system to fight disease.

Just as the body uses IDO to signal the immune system to ignore the presence of a fetus rather than launch an attack, a tumor uses the same mechanism. Once Mellor and Munn realized this crucial role, they developed small-molecule

drugs that inhibit IDO. Augusta University patented the findings, enabling researchers to partner with NewLink Genetics to expedite the drug development. “Our mission is to get these discoveries to patients in Georgia and beyond so they can do some good,” Munn says.

One such drug, which targets brain tumors, was based on Johnson’s work with mice combining the IDO-inhibiting drug, indoximod, with standard chemotherapy.

Augusta University is now conducting clinical trials with drugs such as indoximod on patients who have largely run out of other options. “Brain tumors often can’t be fully removed surgically,” says Johnson, noting that the drug seeks not only to provoke an immune response to the tumor with few side effects, but to battle the resistance cancer can build up against chemotherapy agents. The clinical trial began accepting CONTINUED

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DR. THEODORE JOHNSON

adult patients last spring, and in March, Colin became the first pediatric patient to receive indoximod therapy.

‘A Future for Our Kids’

Funding for the study includes a grant from the Alex’s Lemonade Stand Foundation, named in honor of Alexandra “Alex” Scott, who sold lemonade to raise money for cancer research before dying of cancer at age 8.

Johnson and his team at the Cancer Center also recently received the Cannonball Kids’ cancer Foundation’s inaugural grant. Cannonball Kids’ cancer (with the “c” in cancer deliberately lower-cased to signal its defeatability) is an Orlando, Florida-based nonprofit foundation dedicated to eradicating pediatric cancer.

“This isn’t just funding research, this is funding a future for our kids,” says foundation CoFounder Melissa Wiggins.

Johnson applauds the generosity of foundations such as Cannonball Kids’ cancer and Alex’s Lemonade Stand, noting that brain tumors kill more children annually – nearly 2,700 in the United States alone – than any other cancer. “Funding from organizations like these is critical to advancing innovative immunotherapy research in children,” he says.

Says Dr. Samir Khleif, director of the Cancer

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Center, “Dr. Johnson’s research is a reflection of the level of excellent discovery occurring at the Cancer Center, allowing us to help our patients with the latest innovations of new therapies for adults and pediatrics.”

Making a Footprint

“Dr. Johnson’s clinical trial was especially striking to us,” says Cannonball Kids’ cancer Foundation Co-Founder Michael Wiggins. “Dr. Johnson is going to make a footprint in pediatric immunotherapy, and we are going to help him help kids around the world.”

As the first child in the study, Colin’s footprint will be right beside his.

“I was a little dubious about the study at first,” Toland concedes. “It’s experimental, so I put it on the list of things we might do down the road.

But after Dr. Johnson explained the therapy and the research that had gone into it, my husband and I didn’t really even need to discuss it. We knew that was the next step.”

Either she or her husband accompanies Colin monthly to Augusta for treatment, which consists of oral medication and a checkup.

“Colin loves coming,” Toland says. “Dr. Johnson is completely engaged and very active in all aspects of his treatment, including the parts we receive closer to home. We stay in the

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Ronald McDonald House when we’re in Augusta, which is wonderful, and Colin loves the plane rides. He’s a very social child.”

Mastering His Objective

With more recent revelations about the molecular biology of Colin’s disease, his prognosis is guarded; he’s already lived years longer than science would have predicted. But he recently started third grade, a milestone he couldn’t wait to achieve, and his quality of life is excellent. He’s also laying the groundwork for future pediatric cancer patients. The study is now available for other children, and Colin’s inaugural participation has already added immeasurably to the researchers’ body of knowledge.

Says Toland, “We’re very thankful for this option, because even if it doesn’t cure Colin, it may help extend his life and enhance his quality of life. Right now, that is our goal.”

The family doesn’t discuss mortality with Colin, because his only objective is enjoying his life – an objective he masters with exuberance and aplomb.

“I want him to feel able and accomplished, and that’s what is happening,” Toland says. “Even with everything he has going against him, he’s this incredibly happy kid. I’d like to keep it that way as long as possible.”

Two Visions

Toland, who blogs about her son’s experience (colinlovestractors.com), writes that she carries two visions in her head of son Aidan’s wedding day. In one, she clutches Colin and breaks down in tears, exhilarated that he is there to share the moment. In the other, she hugs Aidan and weeps “over the conspicuous absence in the room.” As difficult as it is, she feels able to accept either outcome. If the latter turns out to be her reality, she and her family will have the comfort of knowing they did everything possible to save him and never took a minute for granted.

“We are extremely fortunate to have Colin with us,” she says. “He has been the beneficiary of the absolutely best treatment and technology. Under normal circumstances, we wouldn’t have had these six years together. We’ve always known this was borrowed time that could be cut short at any moment.”

As she writes in her blog, “Colin’s story is not over and our life as a cancer family will never end. These experiences have changed me as a mother and a human, and not for the worse. We have met incredible people and seen miraculous things. . . . We are grateful for those who work to turn the tide and give hope to children with cancer.”

And as for her older son’s eventual wedding day?

Well . . . “I embrace our joy and gratitude fully, yet always with one eye to that moment in the distant future where tears will mask the unspeakable words, ‘I’m so glad you’re here’ or ‘I wish your brother could have been here.’” n

Research Fall 2015

PRESSING ON The work of Cancer Center pediatric oncologists recently received yet another significant boost.

Press On, a donor-advised fund of the nonprofit

Community Foundation for the CSRA, has donated $2.5 million to fund translational pediatric cancer

research and cutting-edge treatment alternatives at the Cancer Center.

“We are building the infrastructure in Augusta that

can serve communities that don’t necessarily have the ability to travel for treatment,” said Stephen Chance, who co-founded Press On with his wife, Erin.

“When you hear there are no curative options

for your child, it stops you in your tracks,” said Tara

Simkins, who runs Press On with her husband, Turner, and the Chances. “What options can we create for our children? That’s been the driver behind Press On. ”

The gift will fund development of the Press On

Translational Pediatric Oncology Program at the

Cancer Center to boost the discovery and deployment of new treatment alternatives for childhood cancers.

This grant was made possible with the long-term commitment of Tony and Jeannie Loop and the JANUS Research Group.

Press On was founded in 2006 when the Chances’

son, Patrick, was diagnosed with neuroblastoma, a cancer that affects nerve cells. After a courageous

battle, Patrick died in 2012. In 2009, Turner and Tara Simkins joined Press On after their son, Brennan,

was diagnosed with acute myeloid leukemia, a blood

cancer. Following years of care and an unprecedented four bone marrow transplants, Brennan is in remission.

For more information, visit cancer.gru.edu/presson.

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A SCIENTIST AT HEART New President Draws on Lessons Learned in Augusta University Lab “I like to say that even though I gave up my lab, I gained 800 of them.”

That’s the perspective of Augusta University’s new president, Dr. Brooks Keel, as he reflects on his transition from scientist to administrator.

KEEL, WHO JOINED Augusta University in July after serving as president of Georgia Southern University for five and a half years, relishes the challenge of overseeing every aspect of the institution, including its academic and clinical missions. But research will always have a special place in his heart.

He earned both his undergraduate degree and PhD from Augusta University (then Augusta College and the Medical College of Georgia, respectively), and he takes great pride in an alma mater that has made such indelible marks in biomedical research. “I earned my PhD in reproductive endocrinology, a discipline in which MCG has been tremendously influential,” Keel said. “This is where Dr. Robert B. Greenblatt published the first scientific paper on the sequential form of oral contraception.”

Keel had a National Institutes of Health-funded lab for many years, building not only on Greenblatt’s

achievements, but those of other prominent Augusta University researchers, including his mentor, Dr. Tom Abney, and then-Chairman of the Department of Physiology and Endocrinology Virendra Mahesh. Augusta University’s groundbreaking research into reproductive endocrinology continues today, including Dr. Lawrence Layman and colleagues’ identification of four to five genes implicated in delayed puberty (see page 14).

Keel is eager to perpetuate Augusta University’s dynamic research legacy. “I want Augusta University to be a top-50 research institution,” he said. “We need about $30 million more in NIH funding to make that happen. That’s going to be very, very heavy lifting. It won’t happen overnight, but we’ll be on track to get there.”

He plans to invest in “facilities, translational research and people,” ensuring that scientists have the CONTINUED

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SDFGHJK

DR. BROOKS KEEL Research Fall 2015

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time and resources needed to pursue their studies.

“We need to be strategic,” he said of his research goals. “We have real strengths in areas including neurology, cardiology, cancer and pediatric care. Then we have emerging strengths in areas like preventive medicine, public health, personalized medicine/genomics and regenerative medicine. We’re moving toward National Cancer Institute designation, and that will be a huge component.”

He also plans to strengthen existing partnerships while

HE ENVISIONS AUGUSTA UNIVERSITY BECOMING A DESTINATION LOCATION FOR EDUCATION, CLINICAL CARE AND RESEARCH, ATTRACTING THE BEST MINDS NATIONWIDE AND BEYOND.

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cultivating new ones. “I want to see more collaboration, including with other University System of Georgia institutions,” Keel said. “For instance, I’d like to capitalize on engineering research with Georgia Tech and Georgia Southern. We can’t really go down this road on our own. It’s too expensive and resource-intensive to duplicate services or facilities.”

Another key component of Augusta University’s research enterprise is its focus on undergraduate research, he said.

“We’re moving quickly down the path of better integrating our undergraduate and graduatelevel missions,” Keel said. “The opportunity to be president of both my graduate and undergraduate alma mater is incredibly unique.

I find it enormously exciting to oversee a major biomedical research university, and I really appreciate the wonder of an undergraduate campus. There’s a real electricity in this sort of environment. I love being around both sets of students, and one of the great benefits of consolidation is that now we’re able to bring them together as never before. We have vital pipelines in place – and we’re creating more – to expedite undergraduates’ passage into graduate or professional school.”

He is gratified that students have second-to-none educational and research facilities both to learn in and to aspire to. “The Harrison Education Commons, for instance, provides exceptional facilities for our medical and dental students,” Keel said. “And buildings like that are a constant reminder to our undergraduates that that’s where they want to be.”

Keel is also eager to incorporate cutting-edge technology into both biomedical research and clinical

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care. “Technology is a huge component of medicine,” he said. “It won’t be long before three-dimensional printers will be in every operating room.”

He envisions Augusta University becoming a destination location for education, clinical care and research, attracting the best minds nationwide and beyond. As he optimizes existing talent and recruits world-renowned faces onto campus, his most pressing agenda, he says only half-jokingly, is “to give them what they need and keep out of their way when necessary.”

Keel is heartened that the Augusta University faculty and staff seem to share his optimism about unprecedented opportunities on campus, many made possible by consolidation. “Faculty and staff morale is very, very good, and the outlook for the future is incredible,” he said.

“I’ve heard nothing but good things about consolidation. This is a new opportunity to move forward.”

And his inner scientist will always be appreciative of the research he now oversees.

“I now live vicariously through the success of others,” he said. “My job is not just administrator, but facilitator of other people’s goals and dreams.” n

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PRESIDENT KEEL AT A GLANCE l Education: Bachelor of Science degree in biology from Augusta College, doctorate in reproductive endocrinology from the Medical College of Georgia, postdoctoral work at the University of Texas Health Science Center (Houston) and the University of South Dakota School of Medicine (Vermillion) l Previous Position: President, Georgia Southern University l Highlights of GSU Tenure: Launching the Allen E. Paulson College of Engineering and Information Technology and the Institute for Interdisciplinary STEM Education; overseeing the transfer of the Herty Advanced Materials Development Center to GSU l Appointments: Chairman of the American Board of Bioanalysis and member of the Scientific Advisory Board of the American Board of Bioanalysis Proficiency Testing Program, the Georgia Chamber of Commerce and the East Georgia Regional Medical Center Board of Trustees

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DR. LAWRENCE LAYMAN

GROWING PAINS Augusta University Builds On Pioneering Role in Reproductive Endocrinology

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Dr. Lawrence Layman is an expert at treating scars.

And not just the physical kind.

When a patient comes to him because of delayed puberty – the absence of puberty onset in both boys and girls by approximately the midteens – Layman knows that the physical toll is only the tip of the iceberg.

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“DELAYED PUBERTY has not only physical repercussions, but emotional ones as well,” says Layman, who holds the Medical College of Georgia’s Robert B. Greenblatt, M.D. Chair in Endocrinology. “For instance, boys with the condition don’t get facial hair; their voices don’t change. It causes a lot of psychological stress and delayed social development.”

The condition, which affects about 3 percent of children, most commonly results from insufficient gonadal steroid secretion, commonly because of inadequate production of gonadotropin-releasing hormone from the hypothalamus.

Environmental conditions, including malnutrition and some medical therapies to treat other diseases, can cause the condition as well. But it is the body’s altered genetic makeup that most typically steers patients to Layman’s office.

And virtually nowhere in the world are those patients in better hands.

Layman not only treats the condition, but researches it as well. His studies, which have been continuously funded by the National Institutes of Health since 1997, have uncovered four to five genes that possess mutations implicated in the condition – a breakthrough that enables continually improving treatments.

Layman finds it eminently gratifying to chart his patients’ path to wellness – including, in most cases, the ability to procreate – through hormone treatments and other methods. “Treatments are extensive and have side effects, so we’re still trying to find other genes involved in delayed puberty,” he says. “Many of them can be inherited, so the better we can identify them, the better we can not only treat the condition, but help prevent it in future generations.”

Layman, who earned his medical degree from the University of

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Cincinnati, grew intrigued by the condition – as well as others related to reproductive endocrinology – when he accepted a fellowship at the Medical College of Georgia in 1986. He was thrilled to work with Dr. Paul G. McDonough, an esteemed obstetrician/gynecologist, reproductive endocrinologist and geneticist in his own right. But only after arriving did Layman learn that McDonough had trained under one of the preeminent reproductive endocrinologists in the world: Dr. Robert B. Greenblatt.

Greenblatt, for whom the Augusta University Health Sciences Campus library is named, began his career at MCG in 1935 and went on to chair its Department of Endocrinology, the country’s first independent department in the field. By the time he retired in 1972 as a professor emeritus, he had amassed countless contributions to the field, including publishing the first scientific paper on the sequential form of oral contraception – the birth of the birth-control pill. His achievements illuminated many aspects of fertility, including nascent treatments for those unable to conceive. Although it was initially considered to be a breast cancer treatment, Greenblatt found that clomiphene citrate induced ovulation, giving rise to one of the most successful treatments of infertility.

Greenblatt’s pioneering body of work resulted in many honors, including the establishment of MCG’s Robert B. Greenblatt Chair in Endocrinology. Chairs are established with $500,000 endowments, and a Distinguished Chair signifies a $1 million endowment. Donations to the Greenblatt Chair recently elevated its status to a Distinguished Chair.

Layman, who was named to the chair in 2011, is thrilled to perpetuate Greenblatt’s legacy as chief of the MCG Section of

Reproductive Endocrinology, Infertility and Genetics in the MCG Department of Obstetrics and Gynecology.

“When I started training with Dr. McDonough, I realized that MCG’s research wasn’t limited to fertility; the school has a very dynamic program in reproductive endocrine diseases and genetics,” Layman says. “I discovered that those abnormalities and reproductive problems, especially the ones with genetic components, were very interesting to me.”

As proud as he is to hold the chair that bears Greenblatt’s name, he is even prouder of the implications of MCG’s research for future generations and for the international renown of the college’s efforts in the field.

“We study and treat patients from all over the country and beyond,” he says. “They’re tremendously relieved to understand what is wrong with them and to know that help is available.” n

For more information about the Greenblatt Chair or to make a donation, contact: Ralph Alee Augusta University Associate Vice President for Major Gifts 706-721-7343 ralee@gru.edu

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GETTING THE LEAD OUT Research Spurs Advances in Imaging Technology If you’ve ever rushed to the emergency room with the tell-tale chest pain that might signal a heart attack, you’re likely familiar with the extensive technological innovations available to immeasurably improve your odds of survival.

PATIENTS IN technologically advanced hospitals such as the medical center at Augusta University have largely grown inured to such state-of-the-art equipment.

But the people treating the patients and operating the equipment don’t take it for granted for a second.

They maintain immense respect for the resources that aid in diagnosis and treatment – and they’re always on the lookout for improvements.

And Augusta University faculty members occasionally create those improvements themselves.

This has been the case for the past three years as Dr. Gregory

Passmore, professor of medical laboratory, imaging and radiological sciences in the College of Allied Health Sciences, has sought to improve one of cardiology’s foremost diagnostic tools.

“In nuclear cardiology, we use a device called a collimator to image the myocardium, looking for perfusion (the body’s delivery of blood) in heart tissue, particularly the left ventricle,” says Passmore.

The device is a small fixed telescope that produces a parallel beam of radiation. Traditionally, a collimator has used an isotope called thallium 201 to determine CONTINUED

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whether arteries are blocked. If so, the heart’s blood supply is being choked off, imperiling both the heart and life itself. More recently, an isotope called technetium 99m has served as an alternative to thallium.

“There are advantages and disadvantages to each,” Passmore says. “Thallium shows both where the artery is blocked and the health of the muscle tissue around the blockage. If you’ve had a heart attack, you’ll see scar tissue there. If the tissue hasn’t died yet, you can restore blood flow and revive it.”

Technetium, on the other hand, provides higher-resolution images than thallium but can’t adequately determine the health of surrounding tissue. “The resolution is like the difference between old TV sets and highdefinition TV sets,” Passmore says. “With thallium, we have less resolution but know

can compare the images of a stressed heart with those of the heart at rest. “If the images reveal no blockage during rest but reveal blockage during stress, you probably have some plaque buildup,” Passmore says. “A little plaque at rest is generally asymptomatic.

But if you start to exercise, the blockage noticeably expands. That’s when people feel pain in the chest, called angina.” Untreated, of course, the angina can result in a heart attack.

In the second protocol, the patient gets a low-dose of technetium to obtain resting images, then exercises with a higher dose of technetium so new images can be captured and compared.

The third protocol combines the procedures, requiring patients to lie very still in identical positions for each set of images. “We tried injecting the isotopes simultaneously with just one set of images,” Passmore says, “but we realized we had problems with downscatter (the higher-resolution images of technetium scattering down to the area being evaluated).

Doing the images separately is hard on patients,” says Passmore, and it a nationwide shortage –DR. GREGORY PASSMORE exacerbates of technetium. (See page 19.)

The dilemma got Passmore thinking that maybe rather than targeting the isotopes for whether the tissue is viable. Technetium, improvement, the collimator itself could be which uses a higher energy, provides higherimproved. “The collimator camera is made of resolution images but is worse at illuminating lead,” he explains. “Without the lead, it’s like the health of the tissue.” a camera that can’t focus. The camera would One technological advance has been to provide a lot of information, but we wouldn’t combine the protocols, but the solution is be able to interpret it. I thought, ‘If the lead problematic. “You can use them together, is causing the problem, why not find another but you can’t image them at the same time,” material?’”

Passmore says. “This requires taking two sets He has used grants from the Center for of images, which can be hard on patients.”

Undergraduate Research and Scholarship Nonetheless, technicians have made the to do just that. The center provides funding best of it, opting for one of three different for Augusta University research projects protocols, depending on the circumstances. incorporating undergraduates as research In the first, the patient walks on a treadmill, assistants. The funding includes stipends then is injected with thallium so technicians for the undergraduates, who commit to five can capture images on the gamma camera weeks of summer work advancing faculty (the collimator). The patient returns four research. For the past three summers, CURS hours later for more images so the technicians funding has enabled Augusta University

“I THOUGHT, ‘IF THE LEAD IS CAUSING THE PROBLEM, WHY NOT FIND ANOTHER MATERIAL?’”

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AN UNLIKELY PARTNERSHIP Technetium is a vital element in imaging technology, but it’s in short supply.

“We have to import it from other countries,” says Dr. Gregory Passmore, professor of medical laboratory, imaging and radiological sciences, “and problems internationally have greatly curtailed the supply. The problem has been somewhat abated by minimal domestic production, but it hasn’t been sufficient for [imaging specialists’] needs.”

But the fact that domestic molybdenum is available at all is in large part due to the efforts of Passmore, his colleagues and . . . improbably enough . . . a dentist.

“An element called molybdenum degrades to technetium, and molybdenum comes from nuclear reactors,” says Passmore.

His longtime dentist happened to be Dr. Charlie Norwood, who went on to serve in the U.S. Congress from 1995 until his death in 2007. Augusta’s Charlie Norwood Department of Veterans Affairs Medical Center is named in his honor. Norwood, whose dentistry background gave him a tremendous appreciation of imaging technology in health care, championed legislation enabling molybdenum production domestically.

students to assist Passmore with his studies.

This past summer, students Kingsley Anosike, Nathan Gaffney and Richard Stahman participated.

“The students and I tested six different materials as potential replacements for the lead,” Passmore says. “For each material, we looked at the characteristics of attenuation (the percentage of radiation removed because of its interaction with the material).

Five of the six materials we studied worked very well in essentially moving the scatter photon out of the imaging window. Tungsten in particular seems to have the most promise.

It maintains the attenuating characteristics of lead but without the scatter characteristics.”

Of course, tungsten has disadvantages of its own. “Almost any material is more expensive than lead, including tungsten,” Passmore says. “But other elements, including those used mostly in computer circuit boards, worked well too and are less expensive.

Using them for collimators would initially be expensive, but once under production, the

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costs should be reasonable.”

He has presented his findings regionally, statewide and nationwide. “Radiologists have told me the research is very promising and could also be a good substitute for PET (positron emission tomography) scanners, which aren’t necessarily available in some hospitals and which are hard to use on cancer patients with diabetes,” Passmore says.

His next step is to fabricate an imaging model using one or more of the effective elements he tested, then try to interest manufacturers in mass-producing it. “I’m getting estimates now,” Passmore says.

A leap forward in imaging technology made possible largely by the efforts of undergraduates? Passmore notes that this is the beauty of the CURS program. “It’s been wonderful for me to be able to utilize these students,” he says. “The grants gave them the opportunity to participate in research and enabled me to flesh out my ideas.” n

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The Nightmare, 1790–91 by Swiss painter Henry Fuseli ( Johann Heinrich Füssli, 1741 – 1825) Goethe Museum, Frankfurt LT. JIMMY YOUNG AND DR. ALLISON FOLEY

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THE LAW OF THE LAND Nationwide Headlines Inform Perceptions at Local Level It may have been hard to imagine when the United States inaugurated its first African-American president almost eight years ago that convulsive racial unrest would soon follow.

THE TINDERBOX IGNITED in the midst of several recent examples of law enforcement officers’ seemingly unequal treatment of African-American suspects or perpetrators. From the Michael Brown shooting in Ferguson, Missouri, to the apparent suicide of Sandra Bland after being pulled over and subsequently jailed for a minor traffic infraction, throngs of citizens of all races rose up in protest.

As Dr. Allison Foley watched the arrest videos and ensuing publicity along with the rest of the world, she realized just how topical her research was turning out to be.

It was around that time that the Richmond County Sheriff’s Office asked her to help design and implement a survey on citizen satisfaction with their law enforcers’ job performance. Foley, associate professor of criminal justice at Augusta University, eagerly took on the project, which gained more momentum after she received a Center for Undergraduate Research and Scholarship grant. The support from CURS, an Augusta University program incentivizing undergraduate participation in faculty research, enabled Foley to enlist three students to help her launch a pilot survey over the summer.

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LT. JIMMY YOUNG (FROM LEFT), MAJ. SCOTT PEEBLES, JOHNNA KELLEY, DR. ALLISON FOLEY, PAXTON GORDON

“The project initially was part of an internship program with the Richmond County Sheriff’s Office that we’d recently restarted,” explains Foley, an Oklahoma native who joined the faculty eight years ago. “This was in the works before Ferguson occurred. I view it as progressive, especially the desire of the Sheriff’s Office to survey people they’ve actually had contact with.

They really wanted to find out how their officers are doing. I think that’s a bold sign.”

Says Maj. Scott Peebles of the Richmond County Sheriff’s Office, “A key tenant of Sheriff [Richard] Roundtree’s Community-Oriented Policing philosophy is collaboration with the community we serve. By partnering with Augusta University and Dr. Foley’s team, we’re not only building bridges with community stakeholders, but we’re also obtaining valuable feedback from community members we’ve had contact with. That feedback will be used to identify our areas of strength but, more importantly, will tell us where we need to seek improvement.”

Foley brainstormed with the undergraduates – Paxton Gordon, Austin Hendricks and Johnna Kelley – before embarking on the project, guiding them through the process of how to glean the most forthright feedback possible.

“It was important, because the Sheriff’s Office plans to use our findings both in training and monitoring their officers,” Foley says. “This research has real-world implications.”

Foley relished the opportunity to mentor the nascent researchers.

“The students are paid through CURS stipends to work 20 hours a week for five weeks,” she says.

“That’s a lot of time to spend together, and we all ended up getting along great. They really appreciated the opportunity to be involved in research from the very ground level. They knew this was an important partnership and an important service to the community.”

Foley learned from the students as well. “They know the online survey software tool better than I do right now,” she says with a laugh, noting the benefits of working with people who have been computerliterate since preschool.

She and the students started with the hypothesis that their respondents’ attitudes toward the Sheriff’s Office would be most heavily influenced by their most recent encounter with a law enforcement officer. The somewhat random nature of the pilot survey – it was distributed online to 86 people who responded to requests via social media and email to participate – meant that prior encounters with law enforcement wouldn’t be a given.

But as it happened, nearly all the respondents did have experience with law enforcement officers, if only through, say, traffic violations.

(The follow-up study will specifically target those known to have had experiences with Richmond County law enforcers.)

In assessing survey results, Foley and the students indeed uncovered demographic differences in perceptions of law enforcement.

But somewhat unexpected findings materialized as well.

“We certainly found that race

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has an impact,” Foley acknowledges. “And how safe the respondent perceived his own neighborhood to be had an impact. The safer you perceive your neighborhood, the more favorable your opinion tends to be of law enforcement. But by far the most significant predictors of attitude toward law enforcement – more significant even than personal encounters – was the respondent’s attitude toward American police overall.”

While understandable, Foley sympathizes with local law enforcers in dealing with the data. “It’s not particularly surprising, given that everyone is aware of Ferguson and other heavily publicized events,” she says, “but it goes to show that there’s only so much you can do at the local level. What we’re saying is that the most influential factor of people’s attitudes toward your office is something that is quite out of your control. What does that mean for the way they train their officers and trying to build better relationships? They’ll have to be thinking about that and realize this is a really significant factor.”

On the other hand, survey responses also revealed much more manageable data – for instance, the finding that young women were more apt than others to feel patronized by police officers.

“There was more gender-related dissatisfaction than racial-related dissatisfaction,” Foley says. “But keep in mind that surveys tend to generate what you would expect with, say, online restaurant reviews: people either really happy or really unhappy are the ones more likely to respond.

But overall, people are quite satisfied. They perceive Richmond County police officers to be professional and respectful.”

Foley stresses that these preliminary results only hint at what to expect from the larger study to come. “We constructed a survey we’re confident in, and we were happy with the response rate. So we’ve got a lot of good data,” she says. “But it’s only phase one. I’m excited to follow up in more depth. As an educator teaching about crime, it will really be enlightening for me. It’s a way of reaching people in the community with whom we might not normally interact.”

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She notes that the experience is also making the researchers feel more invested in their community. “I do honestly feel a lot more entrenched and grounded in the area than I did before,” Foley says. “Survey respondents are sharing personal stories with us, after all. And this will be really beneficial for my students pursuing law enforcement careers.”

Kelley, one of her undergraduate researchers, stresses that students pursuing other majors will find the research enlightening as well. “I’m a psychology major, but I really enjoyed learning not only more about research in general, but more about sociology and criminal justice,” she says.

“...THE SHERIFF’S OFFICE PLANS TO USE OUR FINDINGS IN BOTH TRAINING AND MONITORING THEIR OFFICERS.” –DR. ALLISON FOLEY “I’ll be applying to graduate schools soon, so I value the opportunity to participate in research projects like this that allow me to learn by working hands on. Dr. Foley is a great teacher, and I look forward to continuing work on this project.”

The citizens themselves, Foley feels, will be the biggest beneficiaries, particularly considering the Richmond County Sheriff’s Office’s willingness to fully embrace the findings in the hopes of serving the community as effectively as possible. “The faith people place in law enforcement is of huge significance,” Foley says. “If they don’t trust the police, they not only are going to be at higher risk for victimization – for instance, because of their reluctance to call for help or report suspicious activity – but they’re going to feel at higher risk.”

Says Foley, “Hopefully, we can find out where the weaknesses are and provide law enforcement a way of enhancing satisfaction.” n

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DR. JOHN HAYES

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‘WHOA DEATH’ Historian’s Look at Folk Religion Unearths Fighting Spirit “In the sweet by and by, we shall meet on that beautiful shore.”

“Oh Death, whoa death, won’t you spare me over ’til another year?”

If your roots are in the rural South, chances are that your great-grandparents grew up singing one set of these lyrics or the other.

But which one? An Augusta University historian thinks he can make an educated guess about your heritage based on the answer.

“THERE’S A STRONG popular conception that the South is very religious; the phrase ‘Bible Belt’ comes to mind,” says Dr. John Hayes, an assistant professor of history who received a summer stipend from the National Endowment for the Humanities to pursue his research. “But historians of the South typically haven’t known how to deal with religion, so there are lots of gaps in our understanding of exactly what that means.”

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Hayes recently completed a monograph – “Hard, Hard Religion: The Other World of the Poor South” – detailing his years of research on the topic in an attempt to close some of those gaps. What he has found is that the Bible Belt traditionally has meant very different things to different groups of people, based largely on socioeconomic status.

“I grew really interested in the topic reading Flannery O’Connor,” says Hayes, noting that the Southern Gothic writer from Milledgeville, Georgia, came much closer than many historians to exploring the role of religion in the lives of Southerners, particularly poor rural Southerners. “I thought, ‘What if I

“THERE’S ALREADY A WIDE BODY OF LITERATURE DEVOTED TO WHITE CHRISTIANITY AND BLACK CHRISTIANITY. THIS IS A THIRD CATEGORY. I WANTED TO UNDERSTAND THE SIGNIFICANCE.” –DR. JOHN HAYES could use O’Connor’s fiction as a window into this unique aspect of the South?’ I wanted to explore the real-world implications.”

He found that in the social, political and economic upheaval in the wake of Reconstruction, most Southerners – both black and white – found solace in the Christian religion that had sustained their forebears for generations. But at that particular juncture in history, Southern society splintered into two distinct cultures. The Southerners of that era who managed to cling to

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the middle class, or even to maintain or build affluence, perpetuated familiar traditions of mainstream Protestantism. That tradition, embodied to this day by the stately, steeple-topped Baptist or Methodist churches ubiquitous to Southern towns, was where the throngs would rhapsodize about the reward of a godly life: heaven: “In the sweet by and by, we shall meet on that beautiful shore.”

But in a parallel universe that was only a stone’s throw away, many of their brethren were living a very different kind of experience – an experience reflected in their culture.

Many newly liberated slaves and grindingly impoverished whites – sharecroppers, coal miners, millworkers – found themselves trying to eke out a subsistence in a society seemingly impervious and indifferent to their struggles. “They were given the message that they had no value, that their lives didn’t matter,” Hayes says.

They begged to differ. They had precious few resources at hand to give voice to their suffering, but they created songs, stories and other means of articulating their experience. This happened in homes and communal gathering spots, including of course churches.

Erecting modest, nondescript folkreligion structures, they gathered not only to share values, but to assert their worth and humanity. As was true of mainstream churches at the time, Hayes notes, they largely segregated by race. But the services of the rural poor, both black and white, tended to have more in common with each other’s than the services unfolding in the gleaming, towering structures dominating town squares.

“There’s already a wide body of literature devoted to white Christianity and black Christianity,” Hayes says. “This is a third category. I wanted to understand A U G U S TA U N I V E R S I T Y

the significance.”

The impoverished Southerners’ commonalities carried over into other areas of life as well, including politics. For instance, in the 1890s, a Georgia orator named Thomas E. Watson managed to briefly galvanize destitute blacks and whites by campaigning for the Populist Party, delivering the thundering message that their poverty was unacceptable.

“This was an underground religious culture,” Hayes says, “a cultural mindset that carried over into politics. It was a cultural response in the face of their denigration – their way of saying, ‘Yes, we do matter.’ It was a way for poor whites and blacks to find common ground and forge a fragile but real connection.”

Although the Bible was front and center in their services, as was true in other Christian churches, folk churches included liberal doses of mysticism and sacramental impulses, such as seeing religious significance in tangible objects, Hayes says. “Their services tended to have more of a passionate and emotive tone,” says Hayes.

The folk culture was primarily transmitted orally, by stories and songs, and the song lyrics were telling. Mainstream Protestants, Hayes says, generally expressed joy and optimism about death, a mere passageway to a glorious afterlife.

But their hardscrabble brethren encouraged each other to find value in the corporeal world that was largely denied them through conventional means. They rejected pat and patronizing assurances from affluent neighbors that reallife privations were unworthy of rectification since they would translate into afterlife treasures.

“A very familiar maxim is Karl Marx’s claim that religion is the opiate of the masses,” Hayes says. “That’s the exact opposite of what I found.”

Instead of accepting their lot in life, folk Christians mobilized, offering Research Fall 2015

mutual support and encouragement.

“Their religion was very much of the real world,” Hayes says. “There was a strong sense of communal neighborliness.”

And the hymns they sang in church – songs popularized nationwide by the 2000 film, “O Brother, Where Art Thou?” – articulated their real-world struggles (“I Am A Man of Constant Sorrow” and “I Am Weary, Let Me Rest,” for instance) while valiantly resisting death or surrender. For instance, the popular folk religion song, “O Death,” intones, “O death . . . you run my life right out of soul.”

Predictably, more affluent Southerners tended to eschew folk culture. “If you do things that make it clear you’re a member of a certain class, the higher classes will distance themselves as much as possible,” Hayes says. “They saw the folk culture as primitive.”

Hayes is pleased that his monograph will add to the body of literature just as the last of folk worshippers are largely dying out.

“There are still some elderly people who remember their parents carrying on folk traditions, but the culture began to unravel in the 1940s,” he says. “By then, the youth were moving away from it.”

He is gratified that many descendants of folk worshippers managed to escape poverty, the condition that created it in the first place, but thinks people have much to learn from those whose voices rose up in modest little churches that today are crumbling to the ground if they still stand at all.

“These people were trying to help each other and prevent social chaos,” Hayes says. “I was aware of the regional poverty that emerged from the Civil War, but I really didn’t understand the lives of the poor. My research gave me a great appreciation not only of their struggles, but of their aspirations.” n

“Hard, Hard Religion” challenges the scholarly consensus and popular conception that religious life in the South divides solely along the “color line.”

It explores how in the society of the New South (1890-1940), poor blacks and poor whites crafted a folk religion that gave voice to sufferings and longings born in poverty. “Hard, Hard Religion” seeks to complicate the scholarship and offer a different portrait of the South by analyzing these interracial class dynamics.

MARGIE CHAPIN

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A WORLD OF WONDER An interactive display that runs the length of a wall in the pediatric imaging suite of the Children’s Hospital of Georgia is among the high-tech, high-touch resources available to GRHealth pediatric patients, including cancer patient Colin Hayward Toland. Read Colin’s story on page 5. The renovated suite, celebrated with an Oct. 20 ribbon-cutting ceremony, helped GRHealth earn a Patient-Centric Imaging Award recently from Health Imaging magazine.

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WILL YOU HELP? MUCH OF THE RESEARCH featured in this edition – as well as countless other research projects unfolding on campus – could not take place without the generosity of donors. As Augusta University Senior Vice President for Research Michael Diamond notes in his introductory letter, this generosity takes all forms – from multimillion-dollar estate gifts to gifts from foundations that got their start as lemonade-stand proceeds. All are important, and all make a real difference in people’s lives. Augusta University’s umbrella foundation, the Medical College of Georgia Foundation, celebrates its 60th anniversary this year – 60 years of advancing research, clinical and educational initiatives at the university. The foundation has amassed endowment assets of over $228 million since its inception, and its impact just keeps growing. To learn more, or to advance Augusta University’s mission with a gift of your own, visit mcgfoundation.org. Thank you in advance for helping us help others. n