A father's gift
Before Jackson Pineda was born, doctors told his parents, Gerald and Jennifer, that their son’s kidneys would not last past the age of 10. A prenatal ultrasound showed one enlarged kidney and the other, they believed, would not be strong enough to make up the difference.
To the couple’s amazement, the doctors’ forecast proved accurate almost to the day.
Doctors had removed the enlarged kidney when Jackson was 2 years old, and his remaining kidney functioned at only half of healthy capacity. By age 4, kidney insufficiency prevented Jackson from growing normally, and daily injections of growth hormone became a way of life.
On Nov. 6, 2010, two days short of his 10th birthday, University Transplant Centersurgeons removed one of Gerald Pineda’s kidneys and placed it in his son’s body.
"We never gave it a second thought," said Gerald Pineda. For years he had known he was a good match to be a donor for his second-oldest son, whenever the time came.
With the transplant center’s Robert Esterl, M.D., leading the team performing Jackson’s surgery, and Kenneth Washburn, M.D., professor of surgery in the Long School of Medicine, leading Gerald Pineda’s team, the transplant took three hours. It was a success.
The University Transplant Center, a clinical partnership of the Health Science Center and the University Health System, offers one of the only pediatric kidney transplant programs in the region. The one-year survival rate for University Transplant Center pediatric kidney patients is 100 percent, according to the Scientific Registry of Transplant Recipients. The one-year survival rate of adult kidney recipients, 94.8 percent, surpasses the national average.
The center also has one-year patient survival rates that exceed national rates in two other signature services, with 85.1 percent for lung transplants and 94.1 percent for liver transplants. The team is the only one in San Antonio to offer the option of living-donor liver transplants.
"I’m very happy with where the University Transplant Center is today," said Glenn Halff, M.D., professor of transplant surgery and director of the center. "It has grown into a mature program that continues to refine the quality of care and medical treatment options that we provide."
Living-donor organs enable children and adults to receive transplants sooner, Dr. Halff said. Roughly 30 percent of transplants at University Hospital involve live donors such as Gerald Pineda. That’s a number the doctors would like to see increase, said Greg Abrahamian, M.D., associate professor of surgery in the Health Science Center's School of Medicine and surgical director of the kidney transplant program.
"We would like to get that up to 50 percent, because the wait time without a living donor is roughly six years in our region," Dr. Abrahamian said. "With living donors, many patients can be transplanted before having to go through dialysis."
That was the case for Jackson.
"He never had to have dialysis because he had a living donor," Jennifer Pineda said. "My husband was willing and able, and spared Jackson from it. We were so fortunate."
And since the majority of kidney donor surgeries are laparoscopic, with only a small incision needed for the donated kidney to be removed, the recovery for Gerald Pineda had resulted in less post-operative pain, a quicker recovery and a shorter time in the hospital.
Both father and son healed well immediately after the transplant, but two months after receiving his new kidney, Jackson was afflicted with a virus infection called BK, which frequently occurs in organ transplant patients and can cause progressive kidneydamage.His nephrologist at the time, Mazen Arar, M.D., medical director of pediatric nephrology with the University Transplant Center, said it was the worst case of BK virus that he’d ever seen, leading to Jackson’s eventual readmission to the hospital with dangerously high blood pressure.
"That was the scariest moment," Gerald Pineda said. "We had this good kidney that we had given him—and we were in danger of losing it."
Thankfully, Jackson’s body responded to treatment. His blood pressure stabilized and his health returned.
Jackson is now 13 and a member of his seventh-grade golf team at San Antonio’s Hector Garcia Middle School. He recently shot a nine-over-par 38 on nine holes, leading all players in a middle school tournament. His skills extend to the fine arts, as well. This year he was recognized as one of the state’s best pianists in his age group.
He’s mellow and carefree, his parents said. And father and son have a few other things in common.
"He loves golf, just like me," Gerald Pineda said. "Whether a shot is good or bad, you can’t tell whether he’s upset."
They don’t talk much about Jackson’s rocky first years. There’s really no need to.
"He’s so normal, you would never know that he had a bad kidney," Gerald Pineda said. "We don’t talk about it very much at all. It’s just part of life."
It takes a team
The University Transplant Center is a clinical and academic partnership with transplants performed at University Hospital by physicians from UT Health San Antonio, the faculty practice of the Long School of Medicine at the UT Health Science Center San Antonio.
"We have an exceptionally knowledgeable and skillful faculty," said Glenn Halff, M.D.,Dielmann Chair in Transplant Sciences, professor of transplant surgery and director of the center. "The team works in a unique multidisciplinary environment that optimizes patient care."
Surgeons include:
- Robert Esterl, M.D.
- Kenneth Washburn, M.D., Valero President’s Distinguished Chair in Transplantation
- Greg Abrahamian, M.D., Joan Wish Endowed Professorship in Transplant Surgery
- Francisco G. Cigarroa, M.D., chancellor of The University of Texas System, who will return full time to the University Transplant Center once his successor as chancellor is named.
The surgeons collaborate with a team of pediatric nephrologists and hepatologists:
- Mazen Arar, M.D.
- Daniel Ranch, M.D.
- Ikuyo Yamaguchi, M.D., Ph.D.
- Naveen Mittal, M.D.
- Jaime Echartea Gonzalez, M.D.
Dr. Halff said the University Transplant Center is successful because of its many partnerships and collaborations.
"Our outcomes are excellent," he said. "For patients who live in this region of Texas, there is no reason to go anywhere else."
An estimated 1,000 South Texans are on the organ recipient wait list. To sign up as an organ donor, go to donatelifetexas.org or call 1-888-336-9633.
Big relief through a hole the size of a dime
Nanette Hathaway well remembers when the pain began. It was Christmas 2009, and she had flown down from Seattle, Wash., to visit her daughter in San Antonio.
"I was in bed when a sharp pain hit my vocal cords and never went away," she said. "The pain was so strong that I couldn’t talk for the whole vacation. I thought it was a flu or something. I went to a pain management place and they guessed it was neuralgia. I kept yelling, help me, help me get rid of this pain."
Doctors put her on hydromorphone, a narcotic analgesic, but the medicine only masked the pain.
"It was like I drank acid through my mouth," she said. "It was the worst pain in the whole world, and eventually it made me want to commit suicide. I lived through it for my children because I always asked myself, what would happen if I did commit suicide? They would have to live with it."
She coped with the pain for four years. Neurosurgeons and ear, nose and throat doctors sent her away with medications and referrals. Then in September 2013, two months after she permanently moved to San Antonio, Hathaway broke her neck in a traffic accident. She was taken to University Hospital where she met David F. Jimenez, M.D., FACS, professor and chairman of the Department of Neurosurgery in the Long School of Medicine at the UT Health Science Center San Antonio.
He repaired her neck, but her vocal cord pain continued. After more rounds of medications and referrals, she returned to Dr. Jimenez for help.
"He looked at an MRI of the brain and showed me where it was abnormal," she said. "He kept me there for at least an hour, showing me all the pictures. He explained it all to me."
A large blood vessel had shifted over her brain stem and was touching a nerve with every pulse of blood. It was fixable, Dr. Jimenez said, and surgery would be minimally invasive.
On March 3, through a hole the size of a dime and with instruments the size of a pencil lead, Dr. Jimenez finally relieved her pain.
A new generation
From the brain to the hands, neurosurgical procedures are going the way of the endoscope, and Department of Neurosurgery faculty members are routinely performing these surgeries at St. Luke’s Baptist Hospital and University Hospital.
Dr. Jimenez is an internationally recognized expert at the neurosurgical use of endoscopy, which offers an internal view of the body using a flexible tube with a small camera attached at the tip. He also is editor of Intracranial Endoscopic Neurosurgery, a textbook published by the American Association of Neurosurgical Surgeons. He wrote three chapters of the book, including one with his wife, Constance M. Barone, M.D., FACS, on endoscopy-assisted surgeries for the management of craniosynostosis.
"Endoscopy is an important and interesting area in neurosurgery today," Dr. Jimenez said. "Instead of performing a full craniotomy with a large bone flap and scar from ear to ear, we can access an area of interest through a hole the size of a dime. We are able to do things inside the brain and spinal cord to alleviate suffering and improve lives. The hole is repaired with a tiny titanium plate that is as thin as a piece of paper but is not vulnerable. The patient can live worry free."
Dr. Jimenez and Dr. Barone, who joined the Health Science Center in 2004 from the University of Missouri, pioneered endoscopic surgery for craniosynostosis, the premature closing of one or more sutures on a baby’s skull. The brain triples in size from birth to 3 years of age and grows tremendously fast in the first six months. To accommodate this expansion, the skull has five elastic sutures, or seams. If even one of the sutures is closed in the womb or at birth, headaches, eye problems and permanent disfigurement can result. The disfigurement occurs because the brain presses on other parts of the skull, resulting in elongation of the head, a bulging forehead and other deformities.
Before endoscopy-assisted craniectomies for craniosynostosis, babies went untreated or their skulls were opened from ear to ear. Dr. Jimenez said the technique remains largely the same, but a new set of endoscopic instrumentation is making it even better. The operation, which once took two hours, is shorter, easier and safer. To date, Dr. Jimenez, Dr. Barone and their surgical teams have treated more than 600 children.
These less-invasive endoscopic approaches help another high-risk population—the elderly.
Dr. Jimenez operated on a 96-year-old woman who could no longer walk to her mailbox because of pain in her back that radiated down to her legs. She had spinal stenosis, a narrowing of the open spaces within the spine that puts pressure on the nerves of the spinal cord. This results in pain, numbness and muscle weakness.
After a short surgery, her pain was eliminated almost instantly, Dr. Jimenez said. Within a month, she was back to bowling and dancing with her boyfriend.
"Traditional surgery is associated with higher risks for elderly patients," Dr. Jimenez said. "Minimally invasive surgery provides an excellent option for this population of patients who otherwise would not be treated and would have to suffer in pain, as was the case with my patient until she had the surgery."
People with carpal tunnel syndrome are experiencing relief through endoscopy, too. In patients suffering from carpel tunnel, the carpal ligament that connects the hand bones becomes thickened and hard through repetitive use such as typing, and this compresses the median nerve, which runs from the spinal cord down to the fingers. This pressure results in severe pain, tingling, numbness and weakness in the palm and ring finger, sometimes extending into the arm, Dr. Jimenez said.
Historically, carpal tunnel release was accomplished with an incision several inches long. Because the hand is very highly sensitive and nerve-rich, patients faced a six- to eight-week recovery with considerable pain. But Dr. Jimenez can free the carpal tunnel through two tiny incisions, inserting a special endoscope. The pain is greatly reduced, and patients recover in one to two weeks.
"I’ve worked on administrators who had endoscopic surgery on a Thursday and went back to work the following Monday," said Dr. Jimenez, who has performed endoscopic carpel tunnel releases for 20 years.
Patients who have had both procedures—open surgery on one hand and endoscopic surgery on the other—said the endoscopic procedure is overwhelmingly better.
"I’ve had a lot of patients who suffered for years, who then had the endoscopy and kicked themselves for waiting," Dr. Jimenez said.
The Department of Neurosurgery is training a new generation of neurosurgeons, and action in 2014 by the Accreditation Council for Graduate Medical Education approved the expansion of the department’s residency program to 17 residents, one of the largest neurosurgery residency programs in the country. Endoscopies are part of their training.
"Every resident who leaves here is capable of doing these surgeries," Dr. Jimenez said, noting that he is establishing the Center for Neurosurgical Endoscopy by July to further education, research and patient care using the minimally invasive approaches.
For patients, this training will be invaluable, he said.
"If you were given the option of having a very invasive and long surgery," Dr. Jimenez asked, "versus one that involves making a hole the size of a dime, what would you rather have?"
A new life
Months removed from her endoscopic surgery, Nanette Hathaway’s outlook is remarkably changed. For the first time in years, the acid feeling in her mouth is gone. She said she is starting to date for the first time in eight years.
Sheknows exactly how long she suffered from the pain: four years and three months. It took years to diagnose her ailment, just two hours to fix it.
While she continues to recover from the dime-size hole and intrusion of endoscopic instruments into her skull, the vocal cord pain is a thing of the past.
"I’m pain-free, it’s gone," she said. "It disappeared immediately after surgery. I was sedated and when I woke up, Dr. Jimenez was right there. He kept asking me, ‘Does your mouth hurt? Is it gone? Is it gone?'"
Hathaway hopes her story will be an encouragement to others who suffer from the same condition, who look normal yet endure pain so unrelenting and severe that it causes suicidal thoughts.
"God gave me the strength, from the love of my children, to stay alive until I found Dr. Jimenez," she said. "Now I’m going to make a difference. I want to start saving lives of people with this disorder."
Learn more about minimally invasive endoscopic surgery.
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Neurosurgery’s history begins with a “Story”
Neurosurgery’s history in the Long School of Medicine dates back to the school’s infancy. The Division of Neurosurgery was founded in 1967 by Jim L. Story, M.D., at the Robert B. Green Hospital in downtown San Antonio. In 1974, the residency training program became fully accredited by the Accreditation Council for Graduate Medical Education (ACGME). Dr. Story trained nearly two dozen neurosurgery residents before his retirement in 1996.
In 2004, the Long School of Medicine recruited David F. Jimenez, M.D., FACS, (pictured above) from the University of Missouri. Since that time, Dr. Jimenez has built a Department of Neurosurgery that has 70 faculty, staff and residents and recently gained ACGME approval to expand to become one of the country’s largest neurosurgery residency programs. The department also obtained authorization to offer a prestigious spine fellowship.
In 2008, Department of Neurosurgery faculty agreed to staff the Baptist Health System’s Brain & Stroke Network, which provides neurosurgery support to stroke victims around the clock, 365 days a year. Prior to the network’s establishment, some stroke patients from Bexar County and the region were transferred to hospitals in other cities when care was not locally available.
Watch an interview of Dr. Story.
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Dr. Xin-Yun Lu: Mentor, mom, scientist
"Mentor," "mom," "scientist" and "game-changer" are fitting words to describe Xin-Yun Lu, M.D., Ph.D., associate professor of pharmacology in the School of Medicine at the Health Science Center. As a devoted mom, Dr. Lu attentively raises her children and steers them on a path toward success. Similarly, as a dedicated researcher, Dr. Lu is consistently raising up scientific discoveries that could pave the way to a novel class of medications for depression. One recent discovery even offers a solid clue as to why the risk of depression is doubled in persons with Type 2 diabetes.
Xin-Yun grew up in Northern China, where she attended medical school at Binzhou not far from Beijing. In 1992 after several years of study, she moved to the United States, where in a few years she completed her Ph.D. at Washington State University and a postdoctoral fellowship at the University of Michigan. Today Dr. Lu is one of the leading women scientists at the Health Science Center. Her novel studies of fat hormones’ role in depression – including the idea that these hormones could treat the disease without the metabolic side effects of current antidepressants – are highly cited by other scientists in journal articles worldwide.
"Fat secretes a lot of hormones, two of which are leptin and adiponectin," Dr. Lu says. "Our team has shed light on their role in mood disorders and their potential as antidepressant agents." In 2006 her lab reported that leptin, which regulates appetite, was decreased in rats that exhibited depression-like behaviors such as anhedonia (reduced pleasure seeking) and learned helplessness. The team’s findings led to more recent discoveries by other scientists that leptin is decreased in a broad spectrum of women with depression.
Another milestone came in 2012 when the lab published its discovery that levels of adiponectin, a circulating hormone that sensitizes the body to insulin, are lower in mice undergoing chronic social stress. When the team injected mice with adiponectin, this effect was reversed. This offers an intriguing connection between diabetes and depression. Current antidepressants raise the risk of obesity and Type 2 diabetes and do not help all depressed patients.
Dr. Lu is raising two daughters, Wendy, now 17, and Jenny, 11, with her husband, Wei Zhang, M.D., Ph.D., a third-year pathology resident in the Long School of Medicine. And even while overseeing a lab that includes four postdoctoral fellows, one Ph.D. student and one junior faculty member, Dr. Lu still finds time for her family’s activities. Since 2003 Dr. Lu has supervised at least 10 postdocs. She also has a lab and is a visiting professor at Binzhou Medical University, the institution that birthed her biomedical career.
Nicole Carrier, Ph.D., learned about Dr. Lu’s research while at the National Institutes of Health. Dr. Carrier is interested in why females are 2.5-times more prone than men to develop depression. "I came here to study gender differences in how leptin affects depression," Dr. Carrier said. "This was the only lab in the country doing this. The novelty is that this lab pioneered the whole idea of leptin in depression."
Jing Liu, Ph.D., instructor/research, said: "I joined Dr. Lu’s lab in 2006 and since then Dr. Lu has been a great mentor for me and a role model of a successful woman scientist. Her research has opened a whole new aspect of understanding mood and emotion regulation by hormones derived from adipocyte (fat). As a brilliant scientist, Dr. Lu’s enthusiasm and complete devotion to scientific research, together with her great wealth of knowledge, inspires and supports everyone in her group. As a respected mentor, she strongly encourages the development of both analytical and grant-obtaining skills, the two critical abilities for future scientific career development. It is exactly the fusion of her passion, charisma, intelligence and the exemplary style of her mentorship that makes me very confident about my future scientific career."
Women scientists lead efforts to fight cancer
Vivienne Rebel, M.D., Ph.D., assistant professor of cellular and structural biology, and Gail Tomlinson, M.D., Ph.D., professor of pediatrics, are two women in science who play crucial roles at the Greehey Children’s Cancer Research Institute. Dr. Rebel dedicates her time to research that could one day translate to new therapies, while Dr. Tomlinson cares for seriously ill children and seeks to translate research discoveries.
Dr. Tomlinson, who holds the Greehey Distinguished Chair in the Genetics of Cancer, is division chief of hematology-oncology. She also holds the Greehey Distinguished Chair for the Children’s Cancer Research Institute Director at the Greehey Institute where she serves as interim director. She sees hospitalized children and has a grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to study pediatric liver cancer. This work is developing into a national and international clinical research trial.
Dr. Rebel investigates the properties of stem cells in a bone marrow disease called myelodysplastic syndrome (MDS). "Stem cells are the only cells in the body that have a seemingly unlimited capacity to proliferate, just like cancer cells," she said. "I thought that by studying stem cells, we may learn about cancer." Dr. Rebel’s laboratory is using a mouse model to try to understand what is going wrong in the production of blood-forming stem cells that may eventually lead to MDS and, in some cases, to leukemia. "It is thought that the culprit cell of MDS is the blood-forming stem cell," she said.
Dr. Tomlinson became intrigued by the molecular basis of cancer while a biochemistry student at Duke University. "I was interested in how some of the biochemical findings could influence the cure of pediatric diseases such as leukemia," she said. "After I became more established, I focused my efforts on understanding genetic causes of pediatric tumors, all with a translational goal in mind to help guide therapies or understand causes so that, whenever possible, diseases could be prevented or detected early. Most pediatric cancers have historically not been thought to be preventable. It is a goal, albeit a long way out."
Dr. Tomlinson is principal investigator on a $2.7 million CPRIT grant to empower health-care providers to map out cancer risks of their patients and to share information about family history as an important factor. The grant, awarded in 2012, also supports screening services for people at high risk for cancer who may not have adequate access to screening.
Dr. Rebel admires women scientists such as Bettie Sue Masters, Ph.D., the Robert A. Welch Foundation Distinguished Chair in Chemistry at the Health Science Center. "Dr. Masters is amazing," Dr. Rebel said. "She has faced the real difficulty of being from a generation when being a woman scientist wasn’t easy. Over time, there has been improvement." Dr. Rebel also greatly respects Dr. Tomlinson for juggling both a clinic schedule and the institute. "I decided to stay with research and not go into the clinic," she said.
As these two women apply their intellect, compassion and resources to understanding pediatric cancers, the children of Texas and the world are the beneficiaries.
Using an infant virus to fight cancer
School of Medicine researchers’ discovery proves effective as cancer treatment
Discoveries in science sometimes come by serendipity, when hard and consistent work done in one area of interest leads to a stunning discovery in a related or even unrelated area. Santanu Bose, Ph.D., associate professor of microbiology and immunology in the Joe R. and Teresa Lozano Long School of Medicine at the Health Science Center, knows by experience that this can happen.
Dr. Bose was studying the immune response of normal and cancerous cells to RSV (respiratory syncytial virus), which causes respiratory infections in infants and young children. Without specifically looking for a cancer treatment, he saw that the virus was "oncolytic" - it preferentially infected and damaged cancer cells while leaving the healthy cells alone. This propelled a new line of research. Dr. Bose teamed with Bandana Chatterjee, Ph.D., of the Long School of Medicine and the South Texas Veterans Health Care System, to test RSV in her mouse model of prostate cancer. Those results again showed a robust anti-cancer effect of RSV. Mice with prostate tumors were treated with the virus and within a week the tumors were gone. "We kept the mice for four months, and the tumors never came back," Dr. Bose said.
Now Dr. Bose is the inventor on a pending U.S. patent of RSV as an oncolytic therapy. This represents a new use for the virus. Dr. Chatterjee, professor of molecular medicine, is the co-inventor. CZ BioMed Corp. of Tampa, Fla., licensed the oncolytic use of RSV in an agreement with South Texas Technology Management (STTM), a regional University of Texas technology-transfer office managed by the Health Science Center. RSV is already showing effectiveness in human trials abroad, according to a company statement.
Dr. Bose, whose work is funded by the National Institutes of Health, said, "This is an exciting development because this is a homegrown invention that is being tested in humans, and therefore this scientific discovery has direct clinical, translational relevance."
"We are pleased that CZ BioMed has agreed to work with us to commercialize Dr. Bose’s and Dr. Chatterjee’s exciting discovery to efficiently target and treat different forms of cancer," said STTM Executive Director Arjun Sanga, J.D., assistant vice president for technology transfer at the Health Science Center.
Dr. Chatterjee said it is significant that the virus killed tumors even in mice with competent immune systems. This mirrors human patients who have functioning immune defenses. RSV also worked whether it was injected directly into the tumor or systemically through the abdomen. "This is important because there are some tumors to which you can inject the drug directly, whereas others you can’t and a drug must work systemically," Dr. Chatterjee said.
Her work on the RSV project is funded by a Merit-Review grant from the U.S. Department of Veterans Affairs (VA), a VA Senior Research Career Scientist Award, and a grant to Drs. Bose and Chatterjee from the National Cancer Institute.
RSV is expected to be safe because it is a children’s virus - it does not infect adults.
It also only infects the lungs. "Normal cells have weapons to shoot down viruses, but cancer cells have lost their anti-viral arsenal," Dr. Bose explained. "For this reason viruses can establish themselves in a tumor, grow and induce cell death."
A press release from CZ BioMed said: "Results from human trials overseas have been extremely successful and exciting to date, with minimal side effects as compared to traditional chemo or radiation therapies." The company’s statement also indicates its plan to conduct a clinical trial with oncolytic RSV in the U.S.
Grants from the San Antonio Life Sciences Institute and the Cancer Therapy & Research Center at the UT Health Science Center San Antonio also supported this research.
Center for Innovation in Drug Discovery translates homegrown discoveries
Taking homegrown discoveries - research findings from laboratories in San Antonio - and turning them into drugs to treat disease is the focus of a new center built through a collaboration between the UT Health Science Center San Antonio and The University of Texas at San Antonio (UTSA). The Center for Innovation in Drug Discovery (CIDD) will help develop drugs out of original discoveries made at the Health Science Center and UTSA to treat all forms of disease and infection.
The earliest phases of pre-clinical drug discovery can take many forms. Unique changes in the behaviors or patterns of protein expression of normal and diseased cells are being used by several laboratories to screen for new drugs to treat cancer
and neurodegenerative and infectious diseases. In addition, high-resolution structural studies at the Health Science Center have identified specific protein targets for therapy in Alzheimer’s disease, Parkinson’s disease, HIV infection, diabetes, cancer and other disorders. Both strategies can be very effective in guiding the design of new drugs, said center Co-Director Bruce Nicholson, Ph.D., professor and chair of biochemistry in the Long School of Medicine at the Health Science Center. The CIDD will facilitate this.
A high-content/high-throughput screening core facility at the Joe R. and Teresa Lozano Long Campus of the Health Science Center, under the direction of Matthew Hart, Ph.D., assistant professor of biochemistry, will enable researchers to use these assays to rapidly sift through thousands of potentially therapeutic compounds in search of lead candidates for the drugs of the future. Analysis and refinements of these lead compounds to make them more effective drugs will then be achieved through a medicinal chemistry core facility under the direction of Doug Frantz, Ph.D., center co-director, and Stanton McHardy, Ph.D., medicinal chemistry core director, located on the West Campus of UTSA.
State and private funding of $3.5 million launched the center. Support from the Texas Legislature enabled renovation of research space and equipment purchases, along with initial operating costs through an award from the San Antonio Life Sciences Institute.
CTSA funding continues to spark translational initiatives
The Clinical & Translational Science Award (CTSA) program, which selected the Health Science Center and its South Texas partners for CTSA funding in 2008, is undergoing an evolution at the National Institutes of Health, where a new institute, the National Center for Advancing Translational Sciences (NCATS), now administers the CTSA program.
The CTSA program at the Health Science Center, under the auspices of the Institute for Integration of Medicine & Science (IIMS), is also evolving in its scope and outreach, said IIMS Director Robert A. Clark, M.D., assistant vice president for clinical research at the Health Science Center.
The IIMS provided CTSA funding to develop electronic health record capability at 24 different practice-based research network sites, a vital lifeline that ties health care providers in the community to academic resources in the Long School of Medicine at the Health Science Center. "We are developing capabilities to pull clinical data from electronic health records at these practices and merge this information with clinical research data," Dr. Clark said.
CTSA funding also makes possible a robust education, training and career development program that developed a translational science Ph.D. program to educate the next cadre of scientists focused on translating research discoveries from bench to bedside. The first five graduate students in the program began course work last fall. The program is in collaboration with UT San Antonio,
UT Austin and the UT Houston School of Public Health.
These and other initiatives - including a pilot projects program supporting research that is jointly funded by various partners - has the CTSA on a continuing high trajectory.
Hyundai Hope on Wheels gives $250,000 to support childhood leukemia research
Hyundai Motor America and local Hyundai dealers brought the Hyundai Hope on Wheels™ program to San Antonio, presenting a $250,000 Hope Grant to scientists in the School of Medicine at the UT Health Science Center San Antonio.
The Hope Grant will support studies of myelodysplasia and leukemia conducted by Alexander Bishop, D.Phil., and Vivienne Rebel, M.D., Ph.D., assistant professors in the Department of Cellular and Structural Biology. These scientists work in laboratories at the Greehey Children’s Cancer Research Institute (CCRI), where Hyundai officials presented an oversized check.
Myelodysplastic syndromes are serious blood cell disorders in which the bone marrow does not function normally. Dr. Rebel said the syndromes are difficult to treat, prompting the search for novel ways to address them.
Dr. Bishop studies DNA repair defects in syndromes such as Bloom’s syndrome, a rare inherited disorder that frequently leads to cancer and often displays myelodysplastic syndrome. DNA, the genetic blueprint in cells, undergoes insults and repair constantly. The insults are from environmental and other factors.
"We’re very excited about this grant," Dr. Bishop said. "We asked whether the cells defective in patients with myelodysplasia have DNA repair defects, and the answer is yes. With this grant we can now ask why."
"Everyone knows someone, perhaps a child, who has been touched by cancer," said Gail Tomlinson, M.D., Ph.D., who holds the Greehey Distinguished Chair in the Genetics of Cancer at the UT Health Science Center. "These university-community relationships are so important."
Outsmarting osteoporosis
Virginia Bowden, Ph.D., loves the slopes of Telluride, Colo., where she and her husband, Charles Bowden, M.D., own a condominium. "We’ve been skiing since the 1970s, currently about 30 days a year," she said. "For me the appeal is the mountain views." In 1997 she fractured her hip while skiing at Winter Park. The bone did not heal after the Colorado surgeon inserted a pin, so the following year she underwent a hip replacement at University Hospital in San Antonio. The surgeon sent a bone specimen for clinical testing, which revealed osteoporosis.
Nearly 40 million Americans suffer from osteoporosis or are at high risk for it, according to the National Institutes of Health. This bone-thinning disease is expected to cause fractures that, by 2025, will have cost patients $25 billion to repair. Osteoporosis is most common in post-menopausal Caucasian women, some of whom live their days with the knowledge that a fracture can result from stumping a toe, getting into bed or sneezing. There is great need for translational research to speed scientific discoveries to patients. Two exciting findings in the Long School of Medicine at the UT Health Science Center San Antonio hold new promise to reduce the suffering caused by bone loss.
Dr. Bowden, director emeritus of the Health Science Center libraries, is a patient of Jan Bruder, M.D., endocrinologist with UT Health Physicians, the clinical practice of the Long School of Medicine. Dr. Bruder sees patients during a weekly osteoporosis consult clinic at the Medical Arts & Research Center. "I’ve been going to Dr. Bruder annually since that time," Dr. Bowden said. "I know what my treatment is, and I think in some ways it was good to find out I had this tendency, so I know to take my calcium, exercise and do the things I should do anyway."
Bone is constantly remodeling — older bone is removed and new bone forms. Exercise places mechanical loads on bone, resulting in a healthy balance of new and old. "The need for regular exercise extends far beyond its role in reducing body fat to maintain a healthy body," said Jean Jiang, Ph.D., professor of biochemistry in the Long School of Medicine and member of the Sam and Ann Barshop Institute for Longevity and Aging Studies. "It is equally important for maintaining healthy bones to avoid osteoporosis and bone loss during aging."
Dr. Jiang’s laboratory discovered novel information about how bones, one, sense the loads being applied to them and, two, release growth factors to build new bone. The report in Proceedings of the National Academy of Sciencesspurred sufficient interest to become an Editor’s Choice article in the journalScience.
Dr. Jiang’s team discovered a lock-and-key system in load-sensing cells. A protein (integrin α5) acts as a key to open the locks, which are channels on the cells’ surface. This releases molecules that trigger bone remodeling. "Our study links the effect of mechanical forces directly to the anabolic (or growth) function of the bone," Dr. Jiang said. "This novel finding could be very useful for development of therapeutic targets to promote the opening of the channels and permit the release of bone growth factors."
Such knowledge could prevent the bone weakening and loss caused by osteoporosis, she said.
Barshop Institute member Brian Herman, Ph.D., is professor of cellular and structural biology in the Long School of Medicine, special assistant to the president of the Health Science Center and a Chancellor’s Health Fellow in Collaboration with The University of Texas System. His team published studies on age-related osteoporosis in mice. The Herman laboratory found that increasing the genetic expression of a protein called caspase 2 prevented osteoporosis development in the rodents. Their bones were 30 percent stronger than the bones of mice lacking caspase 2 expression.
"We are looking at whether caspase 2 can enhance fracture healing," Dr. Herman said. "Our plan is to license technology based on this finding or think about starting a company ourselves."
More-effective, better-tolerated treatments for bone health are needed. Bisphosphonates are the most frequently prescribed medications for osteoporosis. With continuing use, these drugs can cause nausea, abdominal pain, difficulty swallowing and risk of esophageal inflammation and ulcers. In 2010 the National Osteoporosis Foundation issued new treatment recommendations; one was for patients to take drug holidays. "There are side effects of long-term treatment of osteoporosis, and based on bone density and risk factors some people who were previously started on therapy would not be started today," Dr. Bruder, also a Barshop Institute member, said. "This is not to say that patients can go untreated, however. If you need to be on therapy, you need to be on it."
Dr. Bowden served the Health Science Center from 1970 to 2003, including as library director from 1985 to 2003. Her osteoporosis medication is re-evaluated once a year. For three years she received an annual infusion; Dr. Bruder said it was not necessary this year.
The loads from exercise on the Colorado snow continue to strengthen her bones. "I’m still skiing," Dr. Bowden said. "I stick with the intermediate-level areas and try not to fall. I was knocked down this past year on Christmas Eve by a snowboarder and broke my collarbone. The ski patrol came quickly and took me to the clinic. The bone healed within a month and I was skiing again. It (osteoporosis) hasn’t slowed me down."