USF Health preclinical discovery may help identify new therapeutic targets for Alzheimer’s disease, traumatic brain injury and other neurodegenerative diseases

TAMPA, Fla (Nov. 5, 2021) — Neuroinflammatory diseases, including Alzheimer’s disease and traumatic brain injury, have been linked to deposits of a tough protein known as fibrin, derived from the blood clotting factor fibrinogen. These mesh-like fibrin deposits occur outside blood vessels in the brain, contributing to the death of certain central nervous system cells (neurons) that eventually leads to impaired memory.

Now for the first time, a team at the University of South Florida Health (USF Health) Morsani College of Medicine, reported that before soluble fibrinogen is converted into insoluble fibrin molecules that can adversely accumulate, it can connect directly with neurons and cause a damaging inflammatory reaction. The researchers further discovered that fibrinogen specifically binds to two fibrinogen receptors on the surface of neurons: cellular prion protein (PrP^C) and intracellular adhesion molecule-1 (ICAM-1).

USF Health’s David Lominadze, PhD, a professor of surgery and molecular pharmacology and physiology, investigates how microvascular changes induced by neuroinflammation may damage cognition, including short-term memory. | Photo by Allison Long, USF Health Communications.

Their preclinical study was published Sept. 18 in a special issue of MDPI–Biomolecules entitled “Prions and Prion-Like Mechanisms in Disease and Biological Function.”

The findings have implications for identifying targeted therapies to help prevent or stop neurodegeneration in Alzheimer’s disease, traumatic brain injury, or other chronic neuroinflammatory diseases associated with abnormal vascular permeability (leakage) in the brain.

“Fibrinogen is one of the overlooked culprits involved in the processes of neurodegeneration and resulting memory loss,” said principal investigator David Lominadze, PhD, a USF Health professor of surgery, and molecular pharmacology and physiology. “Our study shows that fibrinogen is not only a marker (biological indicator) of inflammation but can be a cause of inflammation in the brain.”

Fibrinogen is a blood plasma protein naturally produced in the liver and travels throughout the bloodstream to other organs and tissues. Outside of blood vessels, fibrinogen is converted by the enzyme thrombin into fibrin during blood clot formation, playing a key role in wound healing.

Dr. Lominadze’s laboratory focuses on understanding molecular changes affecting circulation of blood in the body’s smallest blood vessels — including how microvascular changes induced by inflammation may damage cognition, in particular short-term memory.

Dr. David Lominadze (sitting) with postdoctoral research scholar Nurul Sulimai, PhD (left), and senior biological scientist Jason Brown | Photo by Allison Long, USF Health Communications.

Dr. Lominadze and others have shown that inflammatory disease is associated with a higher concentration of fibrinogen in the blood, increased generation of potentially damaging free radicals, neuronal cell activation and microvascular permeability. In previous studies using their mouse model for mild-to-moderate traumatic brain injury, Dr. Lominadze’s group reported that fibrinogen after crossing the vascular wall accumulated in spaces between the microvessels and astrocytes (another brain cell type connecting vessels and neurons) and activated the astrocytes. This activation coincided with increased neurodegeneration and reduced short-term memory.

In this latest study, the USF Health researchers tested whether fibrinogen, beside interacting with astrocytes, could connect directly with neurons — nerve cells critical for carrying information throughout the human body and coordinating all necessary functions of life.

They treated healthy mouse brain neurons grown in a petri dish with fibrinogen. Fibrinogen increased the death of these neurons, a process that was not influenced by the presence or absence of a thrombin inhibitor preventing the conversion of fibrinogen to fibrin. The finding suggests that soluble fibrinogen and, at later stages, fibrin can have similar toxic effects on neurons.

Furthermore, blocking the function of PrP^C and ICAM-1 fibrinogen receptors on the surface of neurons (essentially stopping fibrinogen from binding tightly to these receptors) reduced inflammatory reactions resulting in neurodegeneration.

“The study revealed that an interaction between fibrinogen and neurons induced an increase in the expression of proinflammatory cytokine interleukin-6, enhanced oxidative damage, and neuronal death, in part due to its direct association (contact) with neuronal PrP^C and ICAM-1,” the study authors wrote.

Interactions of blood plasma protein fibrinogen with its receptors, cellular prion protein (above) and intercellular adhesion molecule (below), on the surface of neurons are shown with red dots using a method called proximity ligation assay.  The presence of red dots indicates interaction of the target protein with its receptor. Neuronal nuclei are shown in blue.  — Microscopic images courtesy of Lominadze Laboratory, USF Health

More research is needed. But altogether the USF Health study suggests that short-term memory problems stemming from neurodegenerative diseases with underlying inflammation may be alleviated by several interventions, Dr. Lominadze said. These include “dampening general inflammation, decreasing fibrinogen concentration in the blood by reducing the synthesis of fibrinogen, and blocking the binding of fibrinogen to its neuron receptors,” he said.

The USF Health research was supported by a grant from the National Heart, Lung and Blood Institute, part of the National Institutes of Health.

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Distinguished USF Health Professor Cesario Borlongan, PhD, is internationally recognized for translational research on the neuroprotective and neurorestorative effects of stem cell therapies in stroke.

Over the last 22 years, his innovative work in the field of neuroscience has encompassed other neurodegenerative diseases and traumatic brain injury as well as stroke.  Dr. Borlongan, director of the Center of Excellence for Aging and Brain Repair at USF, does not hesitate to take calculated risks when it comes to following a different path of inquiry that may lead to a new discovery.

Take, for example, his recent study — with lead author Sandra Acosta, PhD, a postdoctoral fellow in Dr. Borlongan’s laboratory – published in the September issue of the American Heart Association journal Stroke.  The study showed that human bone marrow stem cells intravenously administered to post-stroke rats migrated to the spleen, an abdominal organ that plays a critical role in immune function, and significantly reduced chronic inflammation in the stroke brain.

“Next we want to explore whether transplanting these cells directly into the spleen, rather than peripherally, can lead to better functional recovery, including central nervous system improvement,” Dr. Borlongan said. “Even though stroke is a brain disorder, it has a major peripheral component – and in this case it may be the spleen that should be monitored more closely in our stroke patients.”

USF neuroscientist Cesario Borlongan, PhD, does not hesitate to take calculated risks when it comes to following a different path of inquiry that may lead to a new discovery.

In another study published in the journal PLOS ONE in 2013, Dr. Borlongan and colleagues suggested a new view of how stem cells may help repair the brain following trauma.   In a series of preclinical experiments they reported that transplanted cells appear to build a “biobridge” that links an uninjured brain site where new neural cells are born with the damaged region of the brain.  Based in part on the data reported by Dr. Borlongan’s group, the U.S. Food and Drug Administration approved a limited clinical trial to transplant SanBio 623 cells (an adult stem cell therapy) in patients with traumatic brain injury.  The trial has begun enrolling patients at Stanford University Medical Center.

Additionally, Dr. Borlongan’s bench to bedside research has led to to five FDA-approved clinical trials of cell transplantation in stroke, including the first cell therapy in adult stroke patients.

“One thing that distinguishes our center at USF from many others is its emphasis on translational research” he said. “We like basic science, but we want to see the discoveries in the petri dish translated to animal models of brain disorders and eventually go into the clinics…  At the end of the day, we ask the question:  Can this science be translated into saving lives and make a difference in the lives of patients with stroke and traumatic brain injury?”

National Institutes of Health (NIH) Scientist Emeritus Barry Hoffer, MD, PhD, says despite Dr. Borlongan’s relative youth as a scientist, his insight and creativity has yielded many discoveries advancing the understanding of ischemic brain injury, blood-brain barrier pathophysiology, traumatic brain injury, and stem cell transplantation.

“If I were to make a list of young neuroscientists who are already superstars, Dr. Borlongan would be at the top of my list,” said Dr. Hoffer, an adjunct professor of neurosurgery and proteomics and genomics at Case Western Reserve University School of Medicine.

Dr. Borlogan with Sandra Acosta, PhD, one of the postdoctoral fellows in his laboratory at the USF Center of Excellence for Aging and Brain Repair. “They are the ones who come up with the paradigm-shifting approaches to the experiments and drive the science,” he says of the trainees and students.

Dr. Borlongan has received continuous federal funding totaling more than $15 million from the U.S. Department of Veterans Affairs, the Department of Defense and the NIH since 2002 and also serves as the principal investigator on several industry grants.  Recently, he was awarded a two-year R21 grant from the National Institute of Neurological Disorders and Stroke to study the effects of endothelial stem cells on inflammation in the stroke vasculome — specific genes expressed on the interior surface of blood vessels in the brain following stroke.  The research may have implications for regulating inflammatory genes to treat chronic stroke.

The 30-member laboratory led by Dr. Borlongan includes graduate and doctoral students, a neurosurgery resident, and postdoctoral fellows – emerging scientists who contribute greatly to the research team’s vibrancy, innovation and passion for scientific discoveries.

“We need these young minds to challenge the existing paradigm. They are the ones who come up with the paradigm-shifting approaches to experiments and drive the science,” Dr. Borlongan said.  “I encourage, help facilitate and direct them to the literature, but it’s their show… I try to stay in the background rather than get in their way. That’s the most valuable thing I learned from my mentors.”

He also lets students know that it’s OK when experiments yield unexpected or negative results, because they can learn and move forward even if the initial hypothesis does not hold up. “Be logical, but follow the data; don’t change its direction,” he said. “It may lead you to something novel.”

Dr. Borlonghan with some of the emerging young scientists in his laboratory. They were recently filmed by LabTV.

Dr. Borlongan received his PhD in physiological psychology in 1994 at Keio University in Tokyo, Japan. He pursued fellowships in neuroscience at USF and the NIH, National Institute on Drug Abuse.  He was an associate professor at Medical College of Georgia, where he directed the Department of Neurology Cell Transplantation, before returning to USF as a faculty member in 2008.

He regularly serves on peer review panels for the NIH, VA and the American Heart Association and is an editorial board member for numerous scientific journals, including Cerebral Blood Flow and Metabolism, Stem Cells, PLOS ONE and Brain Research.  He holds several patents for inventions related to investigational cell therapies for brain disorders.

A fellow of the American Association for the Advancement of Science and member of the USF chapter of the National Academy of Inventors, Dr. Borlongan is 2015-16 president of the American Society for Neural Therapy and Repair.

Photos and video by Sandra Roa,  USF Health Communications and Marketing

Umbilical cord cell and growth factor treatment tested in animal models could offer hope for millions, including U.S. war veterans with traumatic brain injuries

USF Health neuroscientist Cesar Borlongan, PhD, the study’s lead author.

Tampa, FL (March 20, 2014) — Traumatic brain injuries (TBI), sustained by close to 2 million Americans annually, including military personnel, are debilitating and devastating for patients and their families. Regardless of severity, those with TBI can suffer a range of motor, behavioral, intellectual and cognitive disabilities over the short or long term. Sadly, clinical treatments for TBI are few and largely ineffective.

In an effort to find an effective therapy, neuroscientists at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery in the USF Health Morsani College of Medicine, University of South Florida, have conducted several preclinical studies aimed at finding combination therapies to improve TBI outcomes.

In their study of several different therapies—alone and in combination—applied to laboratory rats modeled with TBI, the USF researchers found that a combination of human umbilical cord blood cells (hUBCs) and granulocyte colony stimulating factor (G-CSF), a growth factor, was more therapeutic than either administered alone, or each with saline, or saline alone.

The study appeared in a recent issue of PLoS ONE.

“Our results showed that the combined therapy of hUBCs and G-CSF significantly reduced the TBI-induced loss of neuronal cells in the hippocampus,” said study lead author Cesar V. Borlongan, PhD, professor of neurosurgery and director of USF’s Center of Excellence for Aging and Brain Repair. “Therapy with hUBCs and G-CSF alone or in combination produced beneficial results in animals with experimental TBI. G-CSF alone produced only short-lived benefits, while hUBCs alone afforded more robust and stable improvements. However, their combination offered the best motor improvement in the laboratory animals.”

For full story, go to: http://www.research.usf.edu/absolute-news/templates/template1.aspx?articleid=2106&zoneid=1

University of South Florida researchers have suggested a new view of how stem cells may help repair the brain following trauma. In a series of preclinical experiments, they report that transplanted cells appear to build a “biobridge” that links an uninjured brain site where new neural stem cells are born with the damaged region of the brain.

Their findings were recently reported online in the peer-reviewed journal PLOS ONE.

“The transplanted stem cells serve as migratory cues for the brain’s own neurogenic cells, guiding the exodus of these newly formed host cells from their neurogenic niche towards the injured brain tissue,” said principal investigator Cesar Borlongan, PhD, professor and director of the USF Center for Aging and Brain Repair.

A team led by Cesar Borlongan, director of the University of South Florida Center for Aging and Brain Repair, offers a new concept for how transplanted stem cells help prod the brain’s own repair mechanism following traumatic brain injury.

Based in part on the data reported by the USF researchers in this preclinical study, the U.S. Food and Drug Administration recently approved a limited clinical trial to transplant SanBio Inc’s SB632 cells (an adult stem cell therapy) in patients with traumatic brain injury.

Stem cells are undifferentiated, or blank, cells with the potential to give rise to many different cell types that carry out different functions. While the stem cells in adult bone marrow or umbilical cord blood tend to develop into the cells that make up the organ system from which they originated, these multipotent stem cells can be manipulated to take on the characteristics of neural cells.

To date, there have been two widely-held views on how stem cells may work to provide potential treatments for brain damage caused by injury or neurodegenerative disorders.  One school of thought is that stem cells implanted into the brain directly replace dead or dying cells.  The other, more recent view is that transplanted stem cells secrete growth factors that indirectly rescue the injured tissue.

The USF study presents evidence for a third concept of stem-cell mediated brain repair.

The researchers randomly assigned rats with traumatic brain injury and confirmed neurological impairment to one of two groups. One group received transplants of bone marrow-derived stem cells (SB632 cells) into the region of the brain affected by traumatic injury. The other (control group) received a sham procedure in which solution alone was infused into the brain with no implantation of stem cells.

At one and three months post-TBI, the rats receiving stem cell transplants showed significantly better motor and neurological function and reduced brain tissue damage compared to rats receiving no stem cells. These robust improvements were observed even though survival of the transplanted cells was modest and diminished over time.

The researchers then conducted a series of experiments to examine the host brain tissue.

At three months post-traumatic brain injury, the brains of transplanted rats showed massive cell proliferation and differentiation of stem cells into neuron-like cells in the area of injury, the researchers found. This was accompanied by a solid stream of stem cells migrating from the brain’s uninjured subventricular zone — a region where many new stem cells are formed – to the brain’s site of injury.

In contrast, the rats receiving solution alone showed limited proliferation and neural-commitment of stem cells, with only scattered migration to the site of brain injury and virtually no expression of newly formed cells in the subventricular zone. Without the addition of transplanted stem cells, the brain’s self-repair process appeared insufficient to mount a defense against the cascade of traumatic brain injury-induced cell death.

The researchers conclude that the transplanted stem cells create a neurovascular matrix that bridges the long-distance gap between the region in the brain where host neural stem cells arise and the site of injury. This pathway, or “biobridge,” ferries the newly emerging host cells to the specific place in the brain in need of repair, helping promote functional recovery from traumatic brain injury.

Article citation:
“Stem Cell Recruitment of Newly Formed Host Cells via a Successful Seduction? Filling the Gap between Neurogenic Niche and Injured Brain Site;”  Naoki Tajiri, Yuji Kaneko, Kazutaka Shinozuka, Hiroto Ishikawa, Ernest Yankee, Michael McGrogan, Casey Case, and Cesar V. Borlongan; PLOS ONE 8(9): e74857.  Published Sept. 4, 2013.

Research with rat models finds chronic inflammation, suppression of cell regeneration, and neuronal cell loss contribute to wide range of motor and cognitive deficits

TAMPA, FL  (Jan. 4, 2013) – Researchers from the University of South Florida and colleagues at the James A. Haley Veterans’ Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, over time, TBI results in progressive brain deterioration characterized by elevated inflammation and suppressed cell regeneration. However, therapeutic intervention, even in the chronic stage of TBI, may still help prevent cell death.

Their study is published online in the current issue of the journal PLOS ONE.

“In the U.S., an estimated 1.7 million people suffer from traumatic brain injury,” said the study’s senior author Cesar V. Borlongan, PhD, professor and vice chair of the Department of Neurosurgery and Brain Repair at USF.  “In addition, TBI is responsible for 52,000 early deaths, accounts for 30 percent of all injury-related deaths, and costs approximately $52 billion yearly to treat.” 

While TBI is generally considered an acute injury, secondary cell death caused by neuroinflammation and an impaired repair mechanism accompany the injury over time, the authors said. Long-term neurological deficits from TBI related to inflammation may cause more severe secondary injuries and predispose long-term survivors to age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and post-traumatic dementia.

Since the U.S. military has been involved in conflicts in Iraq and Afghanistan, the incidence of traumatic brain injury suffered by troops has increased dramatically, primarily from improvised explosive devices (IEDs), according to Martin Steele, Lieutenant General, U.S. Marine Corps (retired), USF associate vice president for veterans research, and executive director of Military Partnerships. In response, the U.S. Veterans Administration has increasingly focused on TBI research and treatment.

Dr. Cesar Borlongan (left), senior author, and Dr. Paul R. Sanberg, co-author

“Progressive injury to hippocampal, cortical and thalamic regions contributes to long-term cognitive damage post-TBI,” said study co-author Paul R. Sanberg,  PhD, DSc, USF senior vice president for research and innovation and executive director of the Center of Excellence for Aging and Brain Repair at USF Health. “Both military and civilian patients have shown functional and cognitive deficits resulting from TBI.”

Because TBI involves both acute and chronic stages, the researchers noted that animal model research on the chronic stages of TBI could provide insight into identifying therapeutic targets for treatment in the post-acute stage.

“Using animal models of TBI, our study investigated the prolonged pathological outcomes of TBI in different parts of the brain, such as the dorsal striatum, thalamus, corpus callosum white matter, hippocampus and cerebral peduncle,” said Dr. Borlongan, principal investigator for the study. “We found that a massive neuroinflammation after TBI causes a second wave of cell death that impairs cell proliferation and impedes the brain’s regenerative capabilities.”

 Upon examining rat brains eight weeks post-trauma, the researchers found “a significant up-regulation of activated microglia cells, not only in the area of direct trauma, but also in adjacent as well as distant areas.”  The location of inflammation correlated with the cell loss and impaired cell proliferation researchers observed.

Microglia cells act as the first and main form of immune defense in the central nervous system and make up 20 percent of the total glial cell population within the brain. They are distributed across large regions throughout the brain and spinal cord.

“Our study found that cell proliferation was significantly affected by a cascade of neuroinflammatory events in chronic TBI and we identified the susceptibility of newly formed cells within neurologic niches and suppression of neurological repair,” wrote the authors.

The researchers concluded that, while the progressive deterioration of the TBI-affected brain over time suppressed efforts of repair, intervention, even in the chronic stage of TBI injury, could help further deterioration.

The study was supported by the U.S. Department of Defense, the USF Signature Interdisciplinary Program in Neuroscience funds, the USF and Veterans Administration Reintegration Funds, and the USF Neuroscience Collaborative Program.

Citation:  Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Grimmig B, et al. (2013) Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model. PLOS ONE 8(1): e53376. doi:10.1371/journal.pone.0053376

– About USF – 

The University of South Florida is a high-impact, global research university dedicated to student success. USF ranks 50th in the nation for federal expenditures in research and total expenditures in research among all U.S. universities, public or private, according to the National Science Foundation. Serving more than 47,000 students, the USF System has an annual budget of $1.5 billion and an annual economic impact of $3.7 billion. USF is a member of the Big East Athletic Conference.

News release by Randy Fillmore, special to USF Research News

Media contact:
Judy Lowry, USF Research & Innovation
813-974-3181, or jhlowry@usf.edu

Delaying surgical repair reduced secondary brain swelling, damage in TBI animal model

Tampa, FL (March 22, 2012) — Immediate skull reconstruction following trauma that penetrates or creates an indentation in the skull can aggravate brain damage inflicted by the initial injury, a study by a University of South Florida research team reports.  Using a rat model for moderate and severe traumatic brain injury, the researchers also showed that a delay of just two days in the surgical repair of skull defects resulted in significantly less brain swelling and damage.

The study was published March 16, 2012 in the online journal PloS ONE.

While further investigation is needed, the findings have implications for the acute treatment of traumatic brain injury (TBI), considered the signature wound of soldiers who have served in Iraq and Afghanistan, said the study’s principal investigator Cesar Borlongan, PhD, professor and vice chair of research at the USF Health Department of Neurosurgery and Brain Repair.

“A double-edged sword,” is how Borlongan describes the inflammation and subsequent swelling of brain tissue that occurs immediately following TBI.

When the brain is initially penetrated — by a bullet, shrapnel, other debris, or even the force of blast waves, for instance — inflammation helps recruit the body’s own good (glial) cells to the damaged site to limit localized injury. For a short time, the inflammation-induced edema, or swelling of the brain, is beneficial to help relieve pressure within the skull.  However, chronic inflammation precipitates increases in intracranial pressure that perpetuate a vicious cycle leading to secondary cell injury and death.

Cranioplasty is an operation to repair malformations of the skull caused by TBI; the procedure may involve replacing a missing piece of the skull protecting the underlying brain and/or improving the appearance of the skull’s surface.  Current clinical practice emphasizes performing cranioplasty quickly upon initial hospital admission to help reduce the likelihood of infection or other complications that may arise when the brain is exposed.

“Our preclinical study indicates that reconstructing the skull too early in the brain’s natural healing process may interfere with critical therapeutic benefits of brain swelling post-TBI,” Dr. Borlongan said. “It’s better to wait at least two days.”

The USF researchers studied rats with moderate and severe TBI. Post-TBI, the animals were randomly assigned to skull bone flap replacement with or without bone wax (a sterile mixture to help control bleeding from bone surfaces); no skull reconstruction; or delayed skull reconstruction with bone wax alone, which was performed two days following TBI.

The brains of all the animals were analyzed in the laboratory five days after surgery. While immediate reconstruction provided aesthetic repair of the skull fracture, this early surgical procedure, with bone wax alone or with bone wax and skull bone flap, significantly increased cortical brain tissue damage in both moderate and severe animal models.

Overall, whether the rat model was moderate or severe TBI, delayed reconstruction limited the worsening of brain tissue damage compared to immediate reconstruction. In fact, for moderate TBI, the extent of damage observed in the brains of rats that received delayed reconstruction was on a par with that in the animals getting no reconstruction.  In those with severe traumatic brain injury, the tissue damage was significantly larger.  The authors suggest this may mean a two-day delay, while more beneficial than immediate reconstruction, was not sufficient to counteract the intracranial pressure generated by severe TBI.

The researchers concluded that the timing of cranioplasty warrants further evaluation in both laboratory and clinical settings.

“Our results suggest that delaying cranioplasty until the TBI-induced cerebral swelling has subsided may reduce unwanted exacerbation of cortical damage associated with skull reconstruction,” Borlongan said. “We need to carefully weigh the risk of infection that comes from leaving the brain somewhat exposed with the benefit of enhancing the brain’s own repair of its cells.”

“Finding a safe and effective cranioplasty regimen will require determining the optimal period of time when we let the brain repair itself and balancing that with when to best introduce a regimen of surgical skull repair and other potential therapies,” said co-author Harry van Loveren, MD, the David W. Cahill endowed professor and chair of the USF Health Department of Neurosurgery and Brain Repair.

The study was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke, the James and Esther King Foundation for Biomedical Research Program, SanBio Inc., Celgene Cellular Therapeutics, KM Pharmaceutical Consulting and NeuralStem Inc.

Citation:
“Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Damage in Experimental Traumatic Brain Injury Model;” Loren E. Glover, Naoki Tajiri, Tsz Lau, Yuji Kaneko, Harry van Loveren, Cesario V. Borlongan; PloS ONE 7(3), e33646, March 16, 2012.

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USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 34th in federal research expenditures for public universities.

Media contact:
Anne DeLotto Baier, USF Health Communications
(813) 974-3303 or abaier@health.usf.edu

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