The University of Alabama at Birmingham Hospital has received the 2019 America’s Best Hospitals designation from Women’s Choice Award for the practice areas of obstetrics, bariatric surgery, heart care and cancer care and as a best breast center practice.
These areas were awarded based on the hospital’s outstanding achievement in clinical excellence and patient experience and satisfaction. By appearing on the Best Hospitals list, these UAB clinical areas are considered to represent the top 10 percent of hospital practices across the country.
The Women’s Choice Award is an independent referral source for women, aiming to empower women to make better health care choices.
In determining its Best Hospitals list, Women’s Choice Award uses the most recent publicly available information from The Centers for Medicare and Medicaid Services, as well as accreditation information and surveys from thousands of women to determine which measures are most important to them.
Girish Dhall, M.D., has been named as division director for the Hematology-Oncology and Blood Marrow Transplantation program in the University of Alabama at Birmingham Department of Pediatrics and Children’s of Alabama. Dhall is currently an associate professor of pediatrics and director of the Neuro-oncology Program at Children’s Hospital of Los Angeles and will join the department at the end of May 2019.
Dhall has been at CHLA and on faculty at the Keck School of Medicine at the University of Southern California since 2007, when he completed his fellowship in pediatric neuro-oncology. His clinical interests include caring for children and young adults with primary brain and spinal cord injuries. He is dedicated to improving the survival rate of young children with brain tumors without the use of high levels of radiation therapy.
“We look forward to Dr. Dhall building on the strong leadership that has preceded him in the division, and we know that under his direction, the Alabama Center for Childhood Cancer and Blood Disorders will continue to excel in patient care, research and teaching in the years to come,” said Mitch Cohen, M.D., chair of the Department of Pediatrics at the UAB School of Medicine and physician-in-chief of Children’s. “I believe that Dr. Dhall’s leadership of the talented faculty and staff in the Alabama Center for Childhood Cancer and Blood Disorders, as well as the ongoing partnership with the Institute for Cancer Outcomes and Survivorship and the O’Neal Comprehensive Cancer at UAB, will elevate the stature and reach of our pediatric cancer programs and provide great benefit for the children of Alabama, the region and beyond,” Cohen said.
Dhall completed his fellowship in pediatric hematology-oncology at New York University Medical Center, residency in pediatrics at New York Medical College, Valhalla, New York, and medical school at Grant Medical College, Mumbai, India. He is a member of multiple professional societies including Histiocyte Society, American Society of Pediatric Hematology-Oncology, Fellow of American Academy of Pediatrics, Society for Neuro-oncology, American Society of Clinical Oncology, International Society of Pediatric Oncology and the Society for Pediatric Research.
He has successfully led many local and multi-institutional clinical trials and has been involved in many leadership roles on various national committees, including the chairmanship of the Young Investigator’s Committee in Children’s Oncology Group. He has mentored many students, residents, fellows, and junior faculty over the last 10 years who have now taken leadership roles at many prestigious institutions across the country.
“I would like to thank everyone for welcoming Deepti and I to be a part of your UAB family,” said Dhall. “I am excited and truly honored to be among such distinguished group of people. I really look forward to working with all of you and will strive to make Children’s of Alabama and UAB a top destination for children with complex hematologic and oncologic disorders.”
A key step in retroviral growth inside a cell, as described by Jamil Saad, Ph.D., and colleagues, is portrayed on the cover of The Journal of Biological Chemistry. It is a visual image, in molecular detail, of their journal article inside that looks at avian sarcoma virus, or ASV.
The University of Alabama at Birmingham researchers used nuclear magnetic resonance, or NMR, to detail how the matrix domain of the ASV Gag protein binds to certain phospholipids. These phospholipids are vital for Gag protein binding to the plasma membrane of a cell, as the virus replicates and takes its first step toward virus formation and budding.
ASV, a retrovirus that causes cancer in chickens, is the first oncovirus to have been described, more than a century ago. It belongs to the retroviridae family and is closely related to HIV, the virus that causes AIDS. ASV is widely used as a model to study mechanisms of HIV infection and replication. By studying similarities and differences in replication of the two viruses, researchers learn basic knowledge that can inform efforts aimed to halt replication and spread of HIV. Despite great similarities in their Gag proteins that initiate virus assembly, retroviruses have distinct mechanisms for assembly that are incompletely understood.
The work led by Saad, associate professor of microbiology at UAB, and a companion paper, led by Carol Carter, Ph.D., professor of molecular genetics and microbiology at Stony Brook University, examined how the ASV Gag protein is targeted to the plasma membrane of the host cell to initiate virus assembly. Their findings elucidate the plasma membrane binding by the matrix domain of Gag, all the way from determining the precise molecular shape of the protein domain to studying its vital activity in living cells to initiate viral budding.
At UAB, Saad and colleagues elucidated the molecular determinants of ASV matrix interaction with lipids and membranes, and they provided a model of how the matrix binds to a cell membrane.
Important findings included:
- Obtaining a significantly improved structural model of the matrix domain and identifying a membrane binding site that was not obvious in previously determined structures.
- Providing compelling evidence that a cluster of four lysine amino acids in the matrix domain create a basic surface, which acts as a single binding site that directly interacts with acidic membrane lipids called phosphoinositides.
- Demonstrating that Gag-membrane interaction is governed by charge-charge interactions.
They also show that, although the HIV matrix domain uses more structural tools to bind to the membrane, both ASV and HIV matrix proteins share almost identical interacting motifs that drive assembly.
As part of the UAB experiments, the researchers found that replacing lysine residues in the binding site of matrix with a different amino acid greatly diminished binding to lipids and membranes.
In the companion paper, Carter and colleagues at Stony Brook University used those mutations in the matrix domain of the ASV Gag protein to show that disruption of the phosophoinositide binding site on the matrix domain inhibited Gag localization at the cell periphery in two different cell lines and severely reduced viral particle production, as compared with unmutated ASV.
“These studies solved a longstanding mystery on how a virus discovered a century ago utilizes the plasma membrane of the host cell to replicate,” Saad said. “What is even more remarkable is how ASV and HIV-1 share very similar structural features that drive membrane targeting and assembly.”
Co-authors with Saad and Carter on the Journal of Biological Chemistry paper, “Structural basis for targeting avian sarcoma virus Gag polyprotein to the plasma membrane for virus assembly,” are Jiri Vlach, Gunnar N. Eastep and Ruba H. Ghanam, UAB Department of Microbiology; and Susan M. Watanabe, Stony Brook University Department of Molecular Genetics and Microbiology.
This work was supported by National Institutes of Health grant GM117837. The High-Field NMR facility at UAB was established through NIH grant 1S10RR026478 and is currently supported through the O’Neal Comprehensive Cancer Centerat UAB by the NIH grant CA013148.
The companion paper in the Journal of Biological Chemistry is titled “The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery.”
For nearly 200 patients and family members at the University of Alabama at Birmingham Hospital who have received a blood and/or marrow transplantation in the past year, celebrating the holiday season was made a little more cheerful this year.
This December, a luncheon was hosted at UAB Hospital by UAB and BMT Angels of Alabama Foundation, where patients mingled with one another and even received a special visit from Santa and his elves.
“A cancer diagnosis can be a life-changing or -altering traumatic occurrence, for not only for the patients but the families as well,” said Kaitlin Johnson, MSN, R.N., BMTCN, transplant coordinator of Patient Education for Blood and Marrow Transplants. “We give back day to day with our healing hands and through bringing some Christmas cheer, too.”
UAB’s Bone Marrow Transplantation and Cell Therapy Program is one of the leading transplant centers in the region and has performed more than 1,700 transplants since opening in 1991.
John F. Kearney, Ph.D., professor in the University of Alabama at Birmingham’sDepartment of Microbiology, has been named a fellow of the American Association for the Advancement of Science, or AAAS. Election as an AAAS fellow is an honor bestowed upon AAAS members by their peers.
This year, 416 AAAS members won this honor due to their scientifically or socially distinguished efforts to advance science or its applications. Kearney was elected in the Medical Sciences section of AAAS “for his distinguished contributions to immunology, particularly in understanding B cell development and the role of B cells in autoimmune diseases.”
“UAB and the Department of Microbiology are very pleased that Dr. Kearney has been recognized by AAAS for his considerable research achievements during his career here at UAB,” said Fran Lund, Ph.D., chair of Microbiology. “Dr. Kearney’s lab has, over the years, made a number of important discoveries that are revolutionizing how we manipulate the immune system to treat allergies, asthma and autoimmune disease.”
Kearney came to UAB in 1973 and is notable, among other achievements, for his breakthrough paper, “A New Mouse Myeloma Cell Line that Has Lost Immunoglobulin Expression but Permits the Construction of Antibody-Secreting Cell Lines,” in 1979. This foundational study helped create optimal monoclonal antibodies, and it has been cited more than 2,100 times, according to Google Scholar.
Monoclonal antibodies are valuable in both research and medical treatment. The first therapeutic monoclonal antibodies were commercialized in 1986, and global sales were almost $90 billion in 2015.
“Without Dr. Kearney’s seminal studies that allowed for the easy creation of monoclonal antibodies, the new class of anti-cancer ‘checkpoint inhibitor’ biologic drugs could not have been developed,” Lund said. “In many ways, Dr. Kearney’s studies highlight how experiments that were originally designed to advance our understanding of the fundamental principles underlying immunity can also lead to advances in how we treat human disease.
Kearney began his monoclonal antibody work while on sabbatical from UAB in Germany with the noted immunologist Klaus Rajewsky, Ph.D. “As I look back,” Kearney has said of his sabbatical year, “90 percent of the research I have done since has employed monoclonal antibodies made with the cell line I developed at the University of Cologne.”
The new AAAS fellows will be presented with an official certificate and a gold and blue — representing science and engineering, respectively — rosette pin Saturday, Feb. 16, at the 2019 AAAS Annual Meeting in Washington, D.C.
Among his other honors, Kearney was UAB’s 50th Distinguished Faculty Lecturer in 2013.
Other UAB faculty who are AAAS fellows and are current members of AAAS include the following:
- UAB School of Medicine: N. Rama Krishna, Ph.D., Department of Biochemistry and Molecular Genetics; Etty “Tika” Benveniste, Ph.D., Department of Cell, Developmental and Integrative Biology; Bruce Korf, M.D., Ph.D., Department of Genetics; David Briles, Ph.D., and David Chaplin, M.D., Ph.D., Department of Microbiology; Vladimir Parpura, M.D., Ph.D., Department of Neurobiology; and John Smith, M.D., Ph.D., Department of Pathology.
- UAB College of Arts and Sciences: Charles Amsler, Ph.D., Jim McClintock, Ph.D., and Steven Austad, Ph.D., Department of Biology; and Edward Taub, Ph.D., Department of Psychology.
- UAB School of Dentistry: Mary MacDougall, Ph.D., Department of Oral and Maxillofacial Surgery.
O’Neal Industries, Inc., a family-owned global business based in Birmingham, and its shareholders have given the largest single gift in the University of Alabama at Birmingham’s history — a $30 million donation to the Comprehensive Cancer Center — which will allow the center to change the lives of more patients and families through transformational cancer research, patient care, education and prevention.
The center will be known as the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham.
“The O’Neal family has built a legacy in Birmingham, first in the city’s steel industry and now in the city’s future as a biomedical and technology hub,” said Ray L. Watts, M.D., president of UAB. “UAB’s National Cancer Institute-designated Comprehensive Cancer Center is among the pre-eminent cancer centers in the world, and we are proud and grateful that our cancer center will bear the O’Neal name.”
Members of the O’Neal family have been business and political leaders in Alabama for generations. Edward O’Neal was Alabama’s 26th governor, and his son Emmet served as the state’s 34th governor. Kirkman O’Neal was a pioneer in Birmingham’s burgeoning steel industry, founding what was to become O’Neal Steel in 1921. The family now operates O’Neal Industries Inc., the nation’s largest family-owned group of metals service centers.
“We see this gift as an opportunity to give back in a meaningful way to a cause that is important to everyone,” said Craft O’Neal, chairman and CEO of O’Neal Industries and grandson of Kirkman. “We hope the gift will be used in ways that will yield the greatest results, accelerating progress in research, treatment and prevention of cancer and, ultimately, eliminate cancer as a major public health problem.”
The gift and naming will be formally considered for acceptance by the University of Alabama System Board of Trustees at its February meeting.
“This gift will enhance the profile and impact of the cancer center as a premier national destination for those working to end cancer, and those fighting a personal battle with the disease,” said Selwyn Vickers, M.D., senior vice president and dean of the UAB School of Medicine. “It will have lifesaving results that can serve as a catalyst for further philanthropic investment, and we are grateful to the O’Neal family and O’Neal Industries for their leadership in the fight to end cancer.”
The UAB Cancer Center was one of the original eight comprehensive cancer centers established by the National Cancer Act in 1971 and has been continuously funded for 46 years.
“We have made great strides in cancer treatment and prevention in the past several decades,” said Will Ferniany, Ph.D., CEO of the UAB Health System. “In the years ahead, the promise of proton therapy, precision oncology, advanced genomics and new therapeutics should reduce the burden of cancer on individual patients and their families, and on the health care system as a whole. The generous O’Neal gift will be a driving force that transforms cancer care moving forward.”
UAB is the only National Cancer Institute-designated cancer center in its four-state region. It also maintains joint ventures with Russell Medical Center and North Alabama Medical Center and manages the Deep South Network for Cancer Control, an outreach into underserved communities in Alabama and Mississippi. The UAB Health System maintains a Cancer Community Health Network in Alabama, Florida, Georgia and Mississippi.
“This truly transformational gift will have a far-reaching impact on cancer research and patient care in our community, state and region,” said Michael J. Birrer, M.D., Ph.D., director of the center. “It strengthens our clinical operation, expands our cancer research efforts, helps translate discoveries into clinical trials, and further establishes the center as a leader in cancer research and care in the nation. The impact of this gift not only will be felt in the cancer center but will be an economic driver for Birmingham and Alabama.”
The O’Neals’ extended family has been touched by cancer. Kirkman’s son and successor, Emmet, Craft’s father, died from emergency surgery associated with colon cancer, and his daughter Libby O’Neal White was a breast cancer survivor. Her husband, David White, succumbed to cancer, as did Craft O’Neal’s mother Mary Anne and his brother Kirk. Additional members of both the O’Neal and White families have both survived and lost their lives to cancer.
“The O’Neal and White families know too well the devastating effects of cancer, and together we were motivated by the opportunity to play a role in extending the lives of those with cancer in the region, while honoring our family members who have been afflicted by the disease,” O’Neal said.
The O’Neal Comprehensive Cancer Center at UAB is home to more than 400 scientists and physician-scientists and is involved in more than 200 clinical trials of new, promising therapeutics, many using therapies that were developed at UAB. The center treats an estimated 5,000 new patients each year.
The gift will enhance patient access and overall patient care, according to Birrer. Additionally it will expand research efforts, potentially tripling the number of clinical trials conducted at UAB. The gift will also help recruiting efforts of additional investigators and provide leverage for new grant funding.
O’Neal industries and its shareholders have a deep history of philanthropy with UAB. Craft O’Neal is a longtime member of the cancer center’s advisory board, and over the years, O’Neal Industries and family members have supported departments across UAB, including the Comprehensive Cancer Center, the Collat School of Business, the Department of Neurology, the School of Nursing, the Comprehensive Diabetes Center and UAB Athletics.
“Our company has a nearly 100-year history here, and that will continue,” O’Neal said. “We believe in giving back to the community that has been so good to us. UAB is the economic engine of Birmingham and, to a large extent, the state of Alabama. My hope is that others will see the exciting developments at the cancer center and want to invest in its future and that of our city as well.”
Headquartered in Birmingham, O’Neal Industries represents a family of six companies with a global reach. There are 80 separate business locations, including 15 international facilities on four continents, employing more than 3,200 people.
“My grandfather’s and father’s generations of O’Neal employees laid the foundation for the success we enjoy today,” O’Neal said. “This success enables us to give back in all the communities in which we are located, and do even bigger things here at our headquarters in Birmingham. I hope each of our employees, loyal customers and supportive suppliers will take pride in this gift, because without their contributions to our success, we would not be able to give back in such a meaningful way.”
For more information on the impact the gift will have on the cancer center, go to www.uab.edu/news.
The economic impact of a $30 million gift from O’Neal Industries and its shareholders to the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham may be felt four ways, says Michael Birrer, M.D., Ph.D., center director. The gift will help:
- Recruit additional talented cancer scientists and clinicians to UAB, along with the hefty federal grants they garner.
- Expand the number of cancer treatment clinical trials at UAB, an increase that will help patients throughout Alabama and the Southeast.
- Plant the seed for a UAB/Biotech collaboration that can grow into a future Birmingham biotechnology park, much as eastern Cambridge, Massachusetts, has transformed in the past three decades from an aged manufacturing area to a biotechnology boomtown.
- Create a distinctive brand around the center for UAB, Alabama and the Deep South.
All of these can boost UAB’s already considerable impact as the key economic engine for Greater Birmingham.
The $30 million gift will go into an endowment — creating a yearly flexible fund of about $1.5 million that leadership of the cancer center and UAB School of Medicine can use in ways that best leverage further advancement of the cancer center.
“For example,” Birrer said, “let’s say we want to apply for a SPORE grant (Specialized Programs of Research Excellence), the big grants from the National Cancer Institute that focus on a specific organ site or group of cancers. However, in order to do this, we have to hire what I would call a pre-award grants administrator.”
This administrator would be the initial step to help prime the pump toward winning a major grant with multi-year funding.
A similar leveraging opportunity is found in expanding clinical trials at UAB, which will offer hope to cancer patients and bring in dollars, Birrer says. Endowment funds could help hire one or two clinical trials experts, as well as clinical research coordinators, clinical research associates and research nurses. “These kinds of hires are actually not easy,” Birrer said.
Clinical trials that patients want
Expansion of clinical trials — with the goal of increasing the annual accrual of cancer patients from the current 500 new patients a year to 1,500 new patients — will be felt across the Southeast.
“Clinical trials are effectively experiments where you are testing new drugs versus the standard care,” Birrer said. “What the patient would normally get is compared to something new, and this is how the field moves forward. It’s how we discover new effective therapies.”
The center offers a mix of what Birrer calls “different flavors” of trials — including national multi-center trials and drug company-sponsored trials.
Birrer especially favors a third type — early drug development trials — for two reasons that can benefit Birmingham and Alabama.
“The first reason is that’s what patients want,” Birrer said. “Drug development has changed radically over the past 10 to 15 years. It used to be a gamble, in the sense that most drugs fail, and it was a bit of a random chance. Now, with all the molecular biology that we have and all the preclinical testing, the chance that a drug is going to work is much higher, and patients know that.”
“They come here asking for these drugs.”
Best route to economic development
“The other reason,” Birrer said, “and one that is very important from my perspective, is that the companies involved in early drug development are not only Big Pharma but also Biotech,” Birrer said, using the nickname for the biotechnology industry, which has a mix of many smaller players. “I think we can create a UAB/Biotech collaboration here in Birmingham that will help our patients and also drive innovation and revenue for the city.”
“UAB has some high-profile programs like neuroscience and precision medicine,” he said. “But the most branded program at UAB — and the one that has clearest route to economic development in Birmingham — is cancer, unfortunately because it is a common disease and patients need treatments.”
Birrer says he has already found one receptive listener for the concept of a future Birmingham biotechnology park — Birmingham Mayor Randall Woodfin. “The economic impact can be huge,” Birrer said. With the now exploding Biotech industry, I think there is a real opportunity.”
Alabama has a comparative advantage, he says, since labor costs for biotechnology companies in Cambridge are probably twice what they would be in Birmingham. “UAB has 20,000 undergraduates who are well-trained, we have the patient volume, and we have expertise in clinical trials.”
Craft O’Neal, chairman and CEO of O’Neal Industries, says he recognizes the economic impact the $30 million O’Neal gift will make, and suggests the gift may be an impetus to get other philanthropic snowballs rolling.
“My understanding is, for every dollar invested in the cancer center, there is at least a $14 return,” O’Neal said. “That’s pretty spectacular, and I love the fact our gift will help in that regard. It makes me proud, and I’d love to see others come forward with large gifts as well.”
The gift and naming will be formally considered for acceptance by the University of Alabama System Board of Trustees at its February meeting. For more information on the gift, go to www.uab.edu/news.
A two-time childhood cancer survivor, Rusty Duvall will graduate from the University of Alabama at Birmingham with his bachelor’s degree in industrial distribution Saturday, Dec. 15, and start his dream job with the United Parcel Service in January.
When Duvall was 7 years old, physicians found a brain tumor that his parents knew would impact his life. At age 11, Duvall was diagnosed with a rare cancer in the bones of his eye socket.
“Sometimes I feel like my childhood was ripped from me in the blink of an eye,” said Duvall, a senior in the UAB Collat School of Business from St. Clair County, Alabama. “I spent a lot of time in the hospital. I didn’t get to grow up doing a lot of the things that I wanted to do. When I did get to go home, I was really weak and tired.”
Within the first four weeks of his brain tumor diagnosis, Duvall had four surgeries related to the brain tumor and a fifth surgery later that year. At one point, Duvall had fluid leaking from his brain and had to have emergency surgery to place a shunt in order to stop the drainage.
Duvall did not suffer any serious problems from brain surgery, but has felt the lifelong effects from the high dosage of chemotherapy and the surgeries that followed. Duvall has chronic peripheral neuropathy, where the nerves in his right leg are dead, leaving him without muscle strength. He had several surgeries over the course of three and a half years to fix the nerve damage in his leg and eventually help him walk better in the future.
“I have a slight limp when I walk from the lack of muscle strength in my right leg,” Duvall said. “Unfortunately, they were never able to fully repair the nerves, but were able to prevent further damage. My legs and ankles are still very weak.”
The high dosage chemotherapy made Duvall very sick, lose his hair and become extremely underweight. Because of the surgeries and chemotherapy, Duvall missed most of his second- and third-grade years in school. His teachers at Odenville Elementary School made sure he did not miss out on his education by working with his parents to complete assignments at home.
“School was always important to me, but it was hard to keep up with the work during this time,” Duvall said. “I would try my best to get up and go to school, but I was just physically too weak and sick to be there. Luckily, my teachers and my mom helped me through, and I passed both grades.”
Four years later, he was diagnosed with a rare bone cancer near his eye that was completely unrelated to the brain tumor. Duvall was devastated to learn that he had cancer again and became depressed. The physicians at Children’s of Alabama did a biopsy on the bone cancer to determine that it was easily treatable. Duvall underwent two surgeries to remove the cancer and another year of chemotherapy and steroids.
“My parents and I couldn’t believe that we had to go through this again,” Duvall said. “The treatments made me very sick, and I was out of school for most of my sixth-grade year, too.”
Duvall’s teachers worked with him to help him finish up the school year on time. On Aug. 18, 2008, he received his last chemotherapy treatment just in time to start seventh grade. He had 13 surgeries related to the two cancer diagnoses, with the last surgery taking place when he was a senior in high school.
“Cancer has changed me and made me a better person,” Duvall said. “Every day is a new day, and each day is a chance to get better and improve myself.”
In 2005, Duvall started attending Camp Smile-A-Mile, an organization that provides year-round programming that serves children and their families from diagnosis and throughout the years of treatment. Taylor Lawrence was his camp counselor from 2010-2014 and is a UAB Collat School of Business alumni. Lawrence and Duvall discussed his future and what he wanted to do. Lawrence would tell Duvall what college classes were like and the career opportunities that could follow upon graduation.
“I knew I wanted to go to UAB to pursue my degree and secure my future,” Duvall said. “But college was not looking like an option because of financial constraints. My parents worked hard to provide for me and my siblings, but college just seemed far-fetched.”
Upon graduation from St. Clair County High School in 2014, Duvall continued to pursue his dreams of higher education by applying for The Smith Scholarship Foundation, which provides scholarships to deserving Alabama students who have served their communities and have also faced adversity throughout their lives.
“Rusty is the type of person we should all want to be: kind, considerate and dedicated,” said Ahrian Dudley, executive director of the The Smith Scholarship Foundation. “He achieves through perseverance and grit. Securing his degree and job was not easy. Rusty learned to adapt both academically and professionally by maturely dealing with obstacles. He combined his hard work and support systems in place at UAB, the Foundation and community to succeed. He has accomplished more than he dreamed possible when he first set foot on campus. We are so proud of him and the positive impact he has already made on so many people.”
During Duvall’s high school years, he had volunteered and served his community for more than 300 hours. His ability to overcome his challenges, alongside giving back to his community, led to his selection as a Smith Scholar. The scholarship and support programs enabled him to attend UAB and complete his degree.
In the fall of 2014, Duvall started UAB in pursuit of a nursing degree. He had been in and out of hospitals so much as a young child, and thought this was his calling. After speaking with his mentor, Lawrence, he learned about the UAB Collat School of Business’s Industrial Distribution program. During Duvall’s junior year, he switched his major looking to find a career in the business industry.
Duvall received an internship with UPS before his junior year at UAB, where he learned the inner workings of industrial engineering at the Memphis distribution center. Duvall was invited back to intern with UPS before his senior year at the Birmingham distribution center. Upon graduation, Duvall will work at UPS full time as an industrial engineer supervisor.
“The experience I received at UPS really proved that I had taken the right career path,” Duvall said. “When they offered me a job, I couldn’t believe that I achieved my dreams amid all of the challenges I faced as a child.”
Preclinical experiments by University of Alabama at Birminghamresearchers suggest the cancer drugs vorinostat, belinostat and panobinostat might be repurposed to treat infections caused by human papillomaviruses, or HPVs.
HPV infections caused an estimated 266,000 deaths from cervical cancer worldwide in 2012, according to the World Health Organization. Routine screening by Pap smears or HPV DNA tests has reduced death rates in developed countries compared to less developed regions of the globe. Still, an estimated 12,200 United States women are diagnosed with cervical cancer each year.
Highly efficacious vaccines against HPV infection exist — including the recently approved Gardasil 9, which immunizes against nine genotypes of HPV known to cause cervical, vulvar, vaginal and anal cancers, and genital warts. But the vaccine needs to be given before a person becomes sexually active, since it has no therapeutic efficacy against existing HPV infections.
“Safe, effective and inexpensive therapeutic agents are urgently needed,” said N. Sanjib Banerjee, Ph.D., assistant professor of Biochemistry and Molecular Genetics at UAB and lead author of the vorinostat study.
Epithelium of anogenital sites — the cervix, penis and anus — or epithelium of the mouth and throat are sites of HPV infection. But HPVs cannot be propagated in conventional cell culture, hampering the investigation into their pathogenic effects. The laboratory of Louise Chow, Ph.D., and Thomas Broker, Ph.D., in the UAB Department Biochemistry and Molecular Genetics has investigated HPV-host interactions for decades. They discovered that the productive program of HPV depends on differentiation of the epithelium into a full-thickness, squamous epithelium. Furthermore, HPV reactivates host DNA replication in these differentiated cells, such that the replication proteins and substrates become available to support viral DNA amplification.
The Chow and Broker lab re-produced a fully differentiated human squamous epithelium by culturing primary human keratinocytes at an air-media interphase for two to three weeks, a growth they call raft culture. In 2009, their lab developed a breakthrough model for a raft culture of HPV-18-infected primary human keratinocytes, allowing a robust amplification of HPV-18 DNA and production of infective viral progeny. This productive raft culture is an ideal model for preclinical investigation of potential anti-HPV agents.
Banerjee and colleagues hypothesized that inhibitors of histone deacetylases, or HDACs, would inhibit HPV DNA amplification because of their known mechanism of disrupting chromosomal DNA replication. Chromosomal replication requires HDAC alterations of histone proteins, the proteins that act like spools that wind DNA to help package and condense chromosomes and the viral genome. Vorinostat inhibits many HDACs, so it might interrupt not only chromosomal replication but also viral DNA replication.
Using the HPV-18 model raft cultures, the researchers found that vorinostat effectively inhibited HPV-18 DNA amplification and virus production. Importantly, vorinostat also induced the programmed cell death called apoptosis in a fraction of the differentiated cells. Cell death could be attributable to DNA breakage when chromosomal DNA replication was interrupted. Similar results were obtained with two additional HDAC inhibitors, belinostat and panobinostat. In contrast, the differentiated cells of uninfected raft cultures, which do not replicate their DNA, were thus largely spared in the presence of the inhibitors.
The UAB team also examined how vorinostat affected levels and functions of viral oncoproteins, and they described the mechanisms that led to programmed cell death in HPV-18-infected cultures. “On the basis of these detailed studies,” Banerjee said, “we suggest that HDAC inhibitors are promising compounds for treating benign HPV infections, abrogating progeny production and hence interrupting infectious transmission.”
The UAB team also reported that vorinostat caused extensive cell death in raft cultures of dysplastic and cancer cell lines harboring HPV-16. HPV-16 and HPV-18 are the most prevalent, high-risk HPVs responsible for causing anogenital and oropharyngeal cancers. “But further investigation would be required to verify that these agents could also be useful in treating HPV associated dysplasias and cancers,” Banerjee said.
Authors of the paper, “Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification,” published in Proceedings of the National Academy of Sciences, are Banerjee, Chow, Broker and Dianne W. Moore, UAB Department of Biochemistry and Molecular Genetics.
Support came from National Institutes of Health grant CA83679, UAB Comprehensive Cancer Center/HIV-Associated Malignancy Pilot Grant 316851, UAB Comprehensive Cancer Center Pilot Grant 5P30CA013148-43 and UAB Bridge Funding.
At UAB, Chow holds the Anderson Family Chair in Medical Education, Research and Patient Care in the School of Medicine.
Cheri L. Canon, M.D., professor and Witten-Stanley Endowed Chair of Radiology at the University of Alabama at Birmingham, has been named to the American Board of Radiology’s Board of Governors. Desiree E. Morgan, M.D., professor and vice chair for Education in the Department of Radiology at UAB, has been appointed to the American Board of Radiology’s Board of Trustees.
Canon, who previously served the ABR as a trustee, will now serve the board in matters of finance, strategic planning, priority setting, and oversight of American Board of Medical Specialty matters.
Morgan hopes her experience will enable her to improve the abdominal imaging certification process.
“As the abdominal trustee, I plan to help the ABR as it advances the quality, relevance and effectiveness of its exams for initial certification and maintenance of certification across all disciplines of radiology; but my particular expertise will be focused on the gastrointestinal, genitourinary, ultrasound, and reproductive/endocrine radiology arenas,” Morgan said. “The ABR Board of Trustees is responsible for aiding in operational decisions around certification testing, including exam goals, format, content, assembly, delivery, scoring and feedback.”
Canon will serve on the Board of Governors for four years. Morgan will serve on the Board of Trustees for three years.