USF Health researchers applied CRISPR technology to study the very large human non-protein coding gene expressed only in placenta, stem cells and certain cancers

TAMPA, Fla (March 16, 2020) — The placenta, an organ which attaches to the lining of the uterus during pregnancy, supplies maternal oxygen and nutrients to the growing fetus. Abnormal formation and growth of the placenta is considered an underlying cause of various pregnancy complications such as miscarriages, stillbirth, preeclampsia and fetal growth restriction. Yet, much remains to be learned about molecular mechanisms regulating development of this blood-vessel rich organ so vital to the health of a pregnant woman and her developing fetus.

Hana Totary-Jain, PhD, an associate professor of molecular pharmacology and physiology in the USF Health Morsani College of Medicine, was senior author of the study published in Scientific Reports.

University of South Florida Health (USF Health) Morsani College of Medicine researchers recently discovered how a very large human non-protein coding gene regulates epithelial-to-mesenchymal transition (EMT) – a process that contributes to placental development during early pregnancy, but can also promote cancer progression.

During the first trimester, fetal-derived placental cells known as trophoblasts invade the maternal uterine lining and modify its blood vessels to allow oxygenated blood to flow from the mother to fetus. However, trophoblast invasion requires tight regulation of EMT. If inadequate, trophoblast invasion is too shallow to adequately remodel the maternal blood vessels, and adverse pregnancy outcomes can occur. Conversely, excess EMT can cause exaggerated trophoblast invasion through the uterine wall leading to placenta accreta, a condition that can cause hemorrhage and often requires hysterectomy at delivery.

The USF Health researchers used a powerful genome editing technology called CRISPR (shorthand for “CRISPR-dCas9) to activate all of the chromosome 19 microRNA cluster (known as C19MC), so they could study the gene’s function in early pregnancy. C19MC — one of the largest microRNA gene clusters in the human genome — is normally turned off but becomes expressed only in the placenta, embryonic stem cells and certain cancers.

Dr. Totary-Jain discusses the molecular aspects of placenta development and pregnancy complications with research collaborator Umit Kayisli, PhD, a professor of obstetrics and gynecology at USF Health.

In their cell model study, published Feb. 20 in Scientific Reports, a Nature research journal, the USF Health team showed that robust activation of C19MC inhibited EMT gene expression, which has been shown to reduce trophoblast invasion.

But when trophoblast-like cells were exposed to hypoxia – a lack of oxygen similar to that occurring in early placental development — C19MC expression was significantly reduced, the researchers found. The loss of C19MC function causes differentiation of trophoblasts from stem-like epithelial cells into mesenchymal-like cells that can migrate and invade much like metastatic tumors. This EMT process helps explain trophoblast invasion and early placental formation.

“We were the first to use CRISPR to efficiently activate the entire gene, not just a few regions of this huge gene, in human cell lines,” said the paper’s senior author Hana Totary-Jain, PhD, an associate professor in the Department of Molecular Pharmacology and Physiology, USF Health Morsani College of Medicine. “Our study indicates C19MC plays a key role in regulating many genes important in early implantation and placental development and function. The regulation of these genes is critical for proper fetal growth.”

Above: Chromosome 19 microRNA cluster (stained purple) expressed in first-trimester placenta.  Below: In preparation for pregnancy, fetal trophoblast cells (brown) from which the placenta arises invade maternal decidual cells (pink) in the uterus lining. | Images courtesy of Hana Totary-Jain, originally published in Scientific Reports: doi.org/10.1038/s41598-020-59812-8

“You need EMT, but at some point the process needs to cease to prevent adverse pregnancy outcomes,” Dr. Totary-Jain said. “You really need a balance between not enough invasion and too much invasion, and C19MC is important in maintaining that balance.”

Dr. Totary-Jain and others in her department collaborated with colleagues in the medical college’s Department of Obstetrics and Gynecology on the project.

“The USF Health study offers new insight into how trophoblasts interact with the maternal uterine environment to become more invasive or less invasive in the formation of the placenta,” said coauthor Umit Kayisli, PhD, a USF Health professor of Obstetrics and Gynecology. “More research on microRNA expression and how it inhibits EMT may help us better understand the causes and potential prevention of preeclampsia and fetal growth restriction, which account for 5-to-10 percent of all pregnancy complications as well as spontaneous preterm births.”

Investigating the effects of altered C19MC expression on cell differentiation and trophoblast invasion has implications not only for a better understanding of normal and abnormal placental development, but also for cancer and stem cell research, Dr. Totary-Jain added.

Dr. Totary-Jain and Dr. Kayisli

Photos by Freddie Coleman, USF Health Communications and Marketing

Inside the mother’s womb, a fetus exchanges oxygen through the umbilical cord. Once the fetus is delivered, the umbilical cord is clamped, giving the baby the ability to breathe oxygen independently. In rare cases, the fetus has a severe congenital abnormality that obstructs the airway and makes independent breathing after delivery difficult or impossible. Instead of a traditional birth, an innovative surgical procedure, the Ex Utero Intrapartum Treatment (EXIT), is performed to deliver the baby. During this procedure, the baby’s head and shoulders are delivered by an elective Cesarean section, leaving the umbilical cord and placenta intact while pediatricians establish an independent, free airway. After the airway is well established by the pediatricians, the umbilical cord is clamped, and the baby is delivered completely. The procedure may take up to five to ten minutes and requires full coordination between obstetrics, anesthesia, and pediatric teams. USF Health and Tampa General Hospital’s multidisciplinary team performed its first EXIT procedure in 2009 and second in 2016. January 2019 marked the third time in order to deliver a baby with a growth from the tongue that was compressing the airway.

The January 2019 EXIT delivery team featured Sarah Obican, MD, high-risk obstetrician, maternal-fetal medicine subspecialist, who performed the surgery and delivery of the baby in order for the airway to be established. (Photo courtesy of the USF Health Fetal Care Center of Tampa Bay)

“When you do cases of such complexity, you can’t do it alone. You need to have an institution that offers all these subspecialists in one setting and that’s what USF offers,” said Prasad Burjonrappa, MD, MBA, division chief of Pediatric Surgery. Dr. Burjonrappa’s role during the 2019 EXIT procedure was to work alongside Jaime Flores-Torres, MD, neonatologist, to evaluate the infant’s airway and determine if he was a candidate for endotracheal intubation, the placement of a tube into the trachea through the mouth or nose, or if the baby needed a tracheostomy, a surgical procedure to create an opening through the neck into the trachea.

(Left) The baby was born with a growth from the tongue that was compressing his airway. (Right) After the removal of the mass, the baby went home a few days later with no complications. (Photos courtesy of the USF Health Fetal Care Center of Tampa Bay)

An EXIT procedure involves two patients – mother and baby – who each need specialized care to avoid complications. This is why the procedure requires a multidisciplinary team of up to 20 physicians and other health practitioners. With such a large team working together, the procedure needs to be highly coordinated because it’s critical that everyone knows their role, when to act, and how long they have to finish. The USF-TGH team establishes protocols and contingency plans and practices mock surgeries to prepare for every outcome. To ensure the procedure runs smoothly, Anthony Odibo, MD, MSCE, FRCOG, FACOG, director of the USF Health Fetal Care Center of Tampa Bay, oversees and directs the various teams that come together to make the high-risk delivery a success.

“The most challenging part of this is the unknown,” said Sara Zientara, fetal care coordinator for the Fetal Care Center. “You don’t know exactly how that baby is going to come out. You don’t know exactly how that surgery is going to go and you just have to take it as it comes and be able to multitask and problem solve, so preparing everyone for what their role is and could be is important.”

Thanks to the well-established USF Health Fetal Care Center at Tampa General Hospital and the prepared and coordinated team, the January 2019 delivery was yet another success. Once the baby was born and was transferred to an ICU, the baby stayed intubated until the procedure to remove the mass was complete, and then the mother and baby went home a couple of days later without any major complications.

A small part of the EXIT procedure team at the USF Health Fetal Care Center of Tampa Bay located at Tampa General Hospital. (From left to right) Amy Amato, clinician of operations for the TGH women’s operating room, Jaime Flores-Torres, MD, neonatologist, Prasad Burjonrappa, MD, MBA, division chief of Pediatric Surgery, Sarah Obican, MD, high-risk obstetrician, maternal-fetal medicine subspecialist, Sara Zientara, coordinator for the Fetal Care Center, Chinedu Nwabuobi, MD, MS, 3rd-year maternal-fetal medicine fellow. (Photo by Allison Long)

Learn more about the USF Health Fetal Care Center’s multidisciplinary team involved in this EXIT procedure.

Story by Torie Doll. Videos by Torie Doll and Allison Long.

Midwives from USF Health will host a free screening of The Mama Sherpas at 6 p.m., Monday, Sept. 28, at the Center for Advanced Medical Learning and Simulation (CAMLS) second-floor auditorium, 124 S. Franklin St., Tampa, FL 33602.  The documentary will be followed by a panel discussion with midwives, physicians and other representatives from the USF Department of Obstetrics and Gynecology.

The film tells the story of midwives attending births in hospital settings, working in partnership with physicians.  Research has demonstrated that collaborative care models produce better outcomes for mother and baby, including fewer C-sections.  The documentary offers an intimate look at how midwives across the United States work within the hospital system to help improve the birthing process.

The event is open to the public, but please RSVP at https://usfmidwivesmamasherpas.eventbrite.com

Treatment at the USF Health Center builds on leading translational research by Dr. Lockwood’s laboratory team

By Saundra Amrhein

The photographs arrive year after year: cherubic-faced babies, teetering toddlers, precocious kindergartners.

They are reminders to two USF Health doctors of the ultimate outcomes of years of research and struggles that often play out in their offices, the joyful results balanced against quiet frustration and painful loss.

Now, USF Health is announcing a major new initiative through which those doctors and a team of researchers hope to make a dent in the years of futile and heartbreaking attempts of expectant mothers to carry their pregnancy to full term – a hope to ensure that more efforts by area couples end in healthy childbirth.

Last month, USF Health launched The Pregnancy Loss Prevention Center — a clinic lodged at the USF Health South Tampa Center for Advanced Healthcare on the campus of Tampa General Hospital on Davis Islands.

Dr. Charles Lockwood and Dr. Stephanie Romero practice at the new Pregancy Loss Prevention Center, which is housed at the USF Health South Tampa Center for Advanced Healthcare.

At the helm is Dr. Charles Lockwood – the new dean of the USF Morsani School of Medicine and senior vice president for USF Health. His internationally renowned and award-winning research has long focused on preventing premature births, stillbirth, miscarriage and maternal thrombosis. While dean of Ohio State University’s College of Medicine, his institution was one of three Ohio universities and affiliated hospitals to receive a total of $10 million from the March of Dimes to fund the study and prevention of prematurity – which is the leading cause of infant death, blindness, mental disabilities and lung disorders in children.

At USF, he will run the new clinic with Dr. Stephanie Romero, a USF Health obstetrician and gynecologist and an assistant professor of obstetrics and gynecology and maternal fetal medicine. Dr. Romero, also an award-winning researcher, likewise has spent years studying factors – including genetic causes – that lead to pregnancy loss and premature birth.

The multi-disciplinary clinic – which will work with other USF departments and divisions, including genetics, and reproductive endocrinology – will first and foremost seek to give patients a clear and early understanding of what is happening to them so they can better chart a path through treatment or other options, like seeking an egg donor, that are realistic with their circumstances. In doing so, the doctors hope to offer extra office time and individualized care to cut through the uncertainty, anxiety and trauma that so many mothers, couples and families face, sometimes enduring multiple miscarriages and not knowing why or what to do.

“Time is a great resource we can provide, which a busy doctor in daily practice with thirty or forty patients a day can’t do,” says Dr. Lockwood, whose research team – among other accomplishments – has been credited with the development of “fetal fibronectin,” the first biochemical predictor of prematurity.

“That’s the most important ingredient we bring to the table,” he adds. “And also it brings a lot of psychological support, so they know what’s going on. That can have a magical effect on their ability to continue to pursue pregnancy.”

THE CENTER

Dr. Romero walked through the hushed and peaceful hallways of the maternal-fetal division on the fourth floor of the USF South Tampa Center, past examination and ultrasound rooms, stopping to greet and hug a staff member.

It is here where the Pregnancy Loss Prevention Center is based, initially starting out on two Monday mornings a month with plans to eventually expand to once a week as the center’s patient base grows, Dr. Romero said.

Likely to be referred here by physicians, gynecologists, infertility specialists or other medical personnel, patients will have experienced multiple miscarriages, stillbirths or premature births or the risk factors leading to them – from preeclampsia, diabetes and lupus to inflammation and infection.

While studies have shown that 50 percent of all fertile women trying to conceive suffer a miscarriage, about 10 percent of women suffer repeat miscarriages, a rate that increases with age, Dr. Romero said.

The clinic will run examinations on patients – and their partners, if necessary – and conduct laboratory tests to help determine problems or pre-dispositions for troubled pregnancies, she said.

Echoing Dr. Lockwood’s sentiments, Dr. Romero stressed one of the most important factors of the new clinic: quick communication. Patients will not only receive in-depth care, but they will have access to her personal email.

“You really want to get back to them as fast as possible,” she said, adding that the patient’s anxieties as well as physical symptoms need to be addressed right away. “Timeliness is such a big deal, especially at the beginning of pregnancy.”

High levels of anxiety dominate the conversations, she added, and run the risk of further impacting the mother and fetus’ health, as well as determining the patients’ willingness to even attempt another pregnancy.

“You are helping someone through a grieving process,” she said. “I’ve definitely had patients, more than one, say that if it happens again, I can’t go through this again.”

TREATMENT AND SUPPORT

The patients’ trauma from previous losses matched with years of searching in the dark with big unknowns and uncertain outcomes make it essential for the doctors to spend a lot of time with the expectant mothers.

“Some folks don’t even realize it’s a disease entity,” Dr. Romero said. Other times, patients endure multiple miscarriages not knowing they were due to uterine abnormalities, something the center could diagnose and get fixed right away.

“That’s something so easy to correct with surgery. Otherwise you would have no clue,” she said.

Depending on the patients’ conditions and causes for past losses, Dr. Lockwood added, approaches aside from surgery could include everything from heparin and aspirin therapy, to treatment of the immune system, hormone treatments, weight loss and bed rest. A team of researchers working with Dr. Lockwood in laboratories on the USF Tampa campus will be on hand for further investigation of maternal as well as fetal tissue following a miscarriage.

“What we’d like to be able to do is offer detailed genetic analysis, if that’s the explanation,” Dr. Lockwood said. “Or an evaluation for immunology abnormalities, if that’s the explanation.”

For instance, before the 10-week gestation point, most pregnancy losses are due to genetic factors, Dr. Lockwood says. That could include extra copies or deletions of chromosomes passed on to the embryo. The most common feature of such cases is advanced maternal reproductive age. Often such loses are a harbinger of the premature start of menopause – which is, in turn, most influenced by when her mother started menopause. The older her mother was before starting menopause, the longer the patient could likely go before showing higher rates of abnormal chromosomes and miscarriage. On average, if her mother started menopause at the age of 52, the patient could start showing higher chromosome abnormalities by age 35, and by age 40 a miscarriage rate of 50 percent, according to Dr. Lockwood. “However, if her mother was menopausal at 42, increased miscarriage rates may occur at age 30.”

“So it does vary significantly from a biological standpoint,” he added.

Another cause of genetic abnormality is when both parents carry a gene that is lethal to the developing embryo, Dr. Lockwood said.

Between 10 weeks and 20 weeks of gestation, genetic abnormalities are less frequently the cause for miscarriages, and other issues become more prevalent, such as Antiphospholipid antibody syndrome, lupus or other auto-antibody diseases and immunological disorders, he said.

After 20 weeks and before 32 weeks, inherited abnormalities in the cardiac conduction system can result in stillbirths. However, in this timeframe, the most common cause for stillbirths and premature delivery is inflammation and infection, something that can be diagnosed and addressed, Dr. Lockwood said. Other factors include hemorrhaging and stress on the fetus – including when there are twins and triplets.

With a clear diagnosis, he said, the patients can gain a sense of control and make an informed plan about the next step – whether that is with a positive prognosis for another pregnancy attempt or the practical necessity to try something else, such as IVF or an egg donor.

“They get closure,” Dr. Lockwood said. “It may not be good news, but it does provide closure and then helps them make some decisions.”

THE RESEARCH

Last spring when Dr. Lockwood left Ohio State University, where he was dean of the College of Medicine, to take over as dean of USF’s Morsani School of Medicine, he did not come alone. Joining him were three other researchers from his lab, including Dr. Frederick Schatz, who has worked with Dr. Lockwood for 35 years – from New York University to Yale University and then Ohio.

The new Pregnancy Loss Prevention Center at USF is modeled on similar practices Dr. Lockwood has run with his associates at NYU, and Yale and will build on his team’s laboratory research, much of which has been funded by grants from the National Institutes of Health and the March of Dimes Foundation.

A federally-funded Ob-Gyn translational research team working with Dr. Lockwood in laboratories on the USF Tampa campus complements the treatment provided to patients who have experienced multiple miscarriages, stillbirths or premature births or the risk factors leading to them. L to R: Ozlem Guzeloglu-Kayisli, PhD, assistant professor; Frederick Schatz, PhD, professor; Nihan Semerci, biological scientist; and Umit A. Kayisli, PhD, associate professor.

Dr. Schatz and his fellow researchers – Umit Kayisli and Ozlem Guzeloglu-Kayisli – called what they do “translational science” – the goal of taking their discoveries in the laboratory to the clinical level to treat patients.

Ultimately, Dr. Schatz said, their successes in preventing stillbirth and premature births will have a ripple effect that extends out from the immediate families to the entire medical industry and society.

“Statistically it’s a very serious problem,” Dr. Schatz said of prematurity and the disorders and millions of dollars in care it leads to over the course of a lifetime. “It creates a tremendous burden on the health care industry and society.”

In addition to being credited with discovering fetal fibronectin, Dr. Lockwood and his research team have more recently focused on such crucial conditions as preeclampsia – a disease marked by high blood pressure and abnormal protein levels in the urine. Preeclampsia affects between 6 percent and 8 percent of pregnancies in the United States. It is also a major indicator for premature birth, a leading cause of prenatal death and is responsible for 8 percent of maternal deaths, according to a research article by Dr. Lockwood and fellow researchers published in the American Journal of Pathology in September 2013.

Dr. Shatz holds a slide with sections of human placenta immunostained for the presence of the progesterone receptor, which may be related to preterm birth.

A major finding recorded in the research article identifies and describes a specific factor called IP-10 that was found at elevated levels in fluids of first-trimester women. The article calls it a new and “robust” early predictor of preeclampsia – a crucial discovery to help doctors confront a disease that becomes very dangerous in later stages of pregnancy or if left untreated.

Another important area of study for the researchers funded by the March of Dimes has centered on the mechanisms by which progesterone receptor levels suddenly drop during pregnancy, inducing a premature birth.  The research has zeroed in on the correlation or role in these cases of spiking levels of thrombin – the enzyme that facilitates the clotting of blood – and interleukin-1beta, a hormone involved in inflammation.

And most recently, in promising research for which the team has applied to NIH for funding, the group is working with an Ohio State University researcher who has isolated a probiotic in laboratory cultures. The probiotic, incubated with maternal cells, leaves healthy bacteria alone while inhibiting bad bacterial growth. The hope is that the probiotic might one day be able to block in pregnant women the onset of infection and inflammation – the leading causes of premature deliveries between the second and third trimesters.

The probiotic is being used or taken in Europe, but it has not yet been tested on pregnant women, Umit Kayisli said.

While Dr. Lockwood is immersed in all these examples of cutting edge laboratory research, he said he also has drawers full of photographs, cards and letters from happy families that remind him of what is at stake.

“When you do have a healthy baby,” Dr. Lockwood said, “there’s nothing better than that.”

For more information on the Pregnancy Loss Prevention Center or to schedule an appointment, please call (813) 259-8500.

Photos by Eric Younghans, USF Health Communications

USF Health faculty among authors of national study published in Obstetrics and Gynecology

Multistate, hospital-based quality improvement programs can be remarkably effective at reducing early elective deliveries of babies, a study published April 8 in the journal Obstetrics & Gynecology reports.

The March of Dimes, which partly funded the study, calls the findings good news, because babies delivered before full-term are at increased risk of serious health problems and death in their first year of life.

In the group of 25 participating hospitals, the rate of elective early-term deliveries (i.e., inductions of labor and Cesarean sections without a medical reason before a baby reaches a full 39 weeks gestational age) fell significantly from 27.8 percent to 4.8 percent during the one-year project period, an 83 percent decline.

Florida did even better than the other four states involved in the March of Dimes national project, said William Sappenfield, MD, MPH, director of the Lawton and Rhea Chiles Center for Healthy Mothers and Babies at the USF College of Public Health.  Dr. Sappenfield, co-chair of the March of Dimes prematurity initiative, and John Curran, MD, an associate vice president at USF Health and executive director of the Florida Perinatal Quality Collaborative (FPQC), were among the authors of the multistate study.

“The initiative coordinated by the FPQC at USF Health and the Chiles Center reduced the (early-term delivery) rate in Florida’s pilot hospitals to the same low national study rate of 5 percent, even though our state’s pilot hospitals started the initiative with a substantially higher rate of 38 percent,”  said Dr. Sappenfield.  “This would not have been possible without our partnership with the March of Dimes and our obstetrical consultants from Florida’s new district of the American Congress of Obstetricians and Gynecologists.”

L to R: USF leaders of the Florida Perinatal Quality Collaborative include Linda Detman PhD, Department of Community and Family Health at the Chiles Center for Healthy Mothers and Babies; William Sappenfield, MD, MPH, director of the Chiles Center; and USF Health’s John Curran, MD, executive director of the FPQC.

“Reducing unnecessary early deliveries to less than 5 percent in these hospitals means that more babies stayed in the womb longer, which is so important for their growth and development,” said Edward R.B. McCabe, MD, medical director of the March of Dimes.  “This project saw a decrease in the proportion of babies born at 37 and 38 weeks and a corresponding increase in the 39-41 week range during the one-year period studied. Additional studies, perhaps over a longer period of time, could clarify whether such quality improvement programs can also bring down a hospital’s overall preterm birth rate.”

The initiative focused on implementation of a toolkit called “Elimination of Non-medically Indicated (Elective) Deliveries before 39 Weeks Gestational Age,” to guide changes in early term delivery practices.  The toolkit was developed in partnership with March of Dimes, the California Maternal Quality Care Collaborative and the California Maternal Child and Adolescent Division within the California Department of Public Health.

This was the first project of a collaborative with perinatal quality improvement advocates from state health departments, academic health centers, public and private hospitals, and March of Dimes chapters from the five most populous states in the country: California, Florida, Illinois, New York and Texas. These five states account for an estimated 38 percent of all births in the United States.

Florida hospitals participating in FPQC pilot study were St. Joseph’s Hospital in Tampa, Lee Memorial Health System in Ft. Myers, Plantation General Hospital in Plantation, Santa Rosa Medical Center in Milton, South Miami Hospital in Miami, and Broward General Medical Center in Ft. Lauderdale.

The study targeted deliveries that were not medically necessary during the 37th and 38th week of fetal gestation. Even babies born just a few weeks early have higher rates of hospitalization and illness compared to full-term infants.

The six Florida hospitals participating in FPQC pilot study were St. Joseph’s Hospital in Tampa, Lee Memorial Health System in Ft. Myers, Plantation General Hospital in Plantation, Santa Rosa Medical Center in Milton, South Miami Hospital in Miami, and Broward General Medical Center in Ft. Lauderdale.  For an earlier story on USF’s role in the statewide, multihospital initiative, click here.

“This study is only the beginning,” said Dr. Sappenfield, a professor in the USF Department of Community and Family Health. “Not only do other hospitals in Florida need to reduce their rates of non-medically indicated deliveries, but this is the first of many needed perinatal quality improvement initiatives in Florida to assure that all our mothers and infants have access to quality health care.”

The FPQC, in coordination with hospitals, obstetricians, pediatricians, nurses and nurse midwives, is developing new statewide initiatives to reduce preterm births, avert infections and prevent maternal deaths.

The March of Dimes urges hospitals, health care providers, and patients to follow the American College of Obstetricians and Gynecologists guidelines that if a pregnancy is healthy, to wait for labor to begin on its own.  The final weeks of pregnancy are crucial to a baby’s health because many vital organs, including the brain and lungs, are still developing.

“A Multistate Quality Improvement Program to Decrease Elective Deliveries Before 39 Weeks,” by Dr. Bryan T. Oshiro and others, appears in the April 8 online edition of Obstetrics & Gynecology.

The March of Dimes is the leading nonprofit organization for pregnancy and baby health. With chapters nationwide and its premier event, March for Babies, the March of Dimes works to improve the health of babies by preventing birth defects, premature birth and infant mortality. For the latest resources and information, visit marchofdimes.com or nacersano.org.

Anne DeLotto Baier of USF Health Communications contributed to this story.
Photo by Eric Younghans, USF Health Communications