At the 25^th Annual USF Health Research Day, keynote speaker Dr. David Swerdlow of the CDC talked about how lessons learned from the work of disease detectives investigating previous outbreaks –the influenza A (H1N1) virus and Middle East Respiratory Syndrome (MERS) – could be applied to Ebola.

USF Health Research Day 2015 keynote speaker Dr. David Swerdlow, an infectious diseases specialist, helped lead the CDC’s emergency responses to the Influenza A (H1N1) and MERS outbreaks.

Dr. Swerdlow, a medical epidemiologist and associate director for science at the CDC’s National Center for Immunization and Respiratory Diseases, has plenty of experience leading emergency responses at the front lines of emerging infectious diseases. During the H1N1 flu pandemic in 2009 he co-led the field investigation determining how the new virus spread, its severity and causes of death. He also coordinated the CDC’s response to the deadly MERS virus when the first U.S case was identified in 2014.

During the H1N1 pandemic, the CDC periodically produced estimates of the total disease burden associated with infection by the swine-origin virus.

“Rapid epidemiological field investigations are critical for helping answer questions about emerging infectious diseases,” Dr. Swerdlow said. “We found that the severity of H1N1 was much less than that of the 1918 flu pandemic – probably more similar to seasonal influenza.”

Early recognition by the CDC that the highest rates of disease and complications affected younger people in the United States (rather than those 65 and older) was critical to creating pandemic vaccine policies, focusing surveillance strategies, and communicating risks to the public and health care professionals.

The first case of MERS arose in Saudi Arabia in 2012 and spread to other places in the Middle East before the first of two cases hit the U.S. in 2014. The illness, which had a high fatality rate (25-30 percent) and no known treatment, raised global concern.

Led by Dr. Swerdlow, the CDC applied the lessons learned from Severe Acute Respiratory Syndrome, or SARS, to the emergency response operation for MERS.  SARS was another respiratory illness, and close cousin of the MERS virus, that caused more than 8,200 illnesses and about 800 deaths when it arose in China in 2002.

Those lessons included rapid surveillance for identifying cases, making sure patients identified were isolated, quarantines of at-risk health care workers exposed to the MERS virus, and good infection control measures.

“With MERS, we found clear evidence of some person-to-person spread, but not sustained. Camels were likely a source of exposure, but it’s unknown what proportion of cases has camel exposure,” Dr. Swerdlow said.  “We also found many people were getting sick by exposure to health care workers, so there was an amplification of illness from this population.”

Finally, speaking about the recent Ebola epidemic, “the largest of its kind in history,” Dr. Swerdlow said most cases were and still are confined to Guinea, Liberia and Sierra Leone.

To help contain the epidemic, the CDC worked with international partners and focused on providing technical assistance in surrounding African countries identified by the World Health Organization as being at increased risk of Ebola.  Among its activities, the agency enhanced entry screening at airports, tracked travelers from the three highest-risk countries who came to the U.S., and tightened infection control guideline for health care workers.

The number of new Ebola infections in West Africa has declined sharply since late last year, but Dr. Swerdlow and others tracking the outbreak are hesitant to say the deadly hemorrhagic disease is done.

“Everyone is thrilled the Ebola cases have decreased dramatically, but getting to zero is going to be more difficult,” he said. “There are challenges, largely because of an overburdened health care system in these West African countries – unpaid health care workers, insufficient treatment centers, medical supplies and personal protective equipment.”

Dr. Swerdlow concluded that epidemiological research is vital for understanding how to help prevent geographic spread of epidemics and effectively respond to future global health security threats.

“The risk remains,” he said.” We live in a very interconnected world where diseases are only a flight away.”

Photo by Eric Younghans, USF Health Communications

RELATED STORY:
USF Health News 25th USF Health Research Day: A celebration of research and collaboration

The  academic outlets relied upon to disseminate science  often have limited influence on contemporary cultural or policy debates.  Are there ways to promote your findings and ideas to a broader audience?

An upcoming workshop sponsored by the USF Office of Community Engagement and Partnerships will focus on ways to get your research off the shelf and into the public discourse.

The  “GoPublic!” workshop will be held from 10 a,m. to noon, Thursday, Oct. 23, in the USF Health Morsani College of Medicine’s Group Learning Space (2,4 and 6).   The workshop will be led by Vickie Chachere, director of special projects, University Communications and Marketing, and Wayne Garcia, associate director of the USF School of Mass Communications and instructor in journalism.

Workshop attendees will learn how to:

• Frame academic research for a broader public
• Build partnerships with newspapers and other media outlets.
• Be proactive with the news media by framing and defining issues under public discussion.
• Provide expertise for op-ed pages.
• Translate academic discourse into plain language.
• Compose newsworthy narratives that correct misinformation and misunderstandings in the public discussion.

So, save the date if  you are interested in learning how to communicate clearly and vividly about your scientific work and why it matters.

The workshop is free; however a reservation is requested.  Please CLICK HERE to RSVP.   For more information, contact the Office of Community Engagement at 813-974-3233, or e-mail communityengagement@usf.edu.

It’s an impressive testament to the center’s emphasis on a community-based participatory research model – one that listens to what people in communities need and translates the research into effective public health practices and policies to improve health.  The successful model has produced social marketing interventions to reduce eye injuries in citrus workers, prevent smoking and underage drinking in middle-school students and get children to be more physically active and eat better.

Still, nothing is guaranteed in a new highly-competitive funding cycle.

The stakes are even higher when the number of federal grant proposals continues to swell while the funding available shrinks.  This time around the Centers for Disease Control (CDC) would cut from 37 to 26 the number of prevention research centers in its prestigious nationwide network.

FPRC Director Carol Bryant, PhD, told the Tampa Bay Business Journal she breathed a sigh of relief when USF’s proposal scored highly and ultimately beat out some stiff competition to secure $750,000 for the first year of a new center grant. The CDC grant will total $4.35 million over five years.

“Some of the more prestigious institutions that have had centers in the past were not selected this year,” Bryant said.  “Most notable and surprising were Harvard, Emory, the University of Michigan, University of Wisconsin, University of Texas, and University of California at San Diego.”

USF also beat out the University of Florida, which gave FPRC its first in-state competition.

The Florida Prevention Research Center, based at the USF College of Public Health, is led by Carol Bryant, center right, and Julie Baldwin, center left.

The win took a strategic team effort.

“The USF College of Public Health’s prevention research center benefits from our longstanding and deep relationship with the Florida Department of Health. Their active involvement in planning and developing the proposal, we believe, was instrumental in our success,” said Donna Petersen, ScD, dean of the College of Public Health.

“And, there is no better team than the one led by Drs. Carol Bryant and Julie Baldwin. These seasoned scholars and public health professionals know how to promote health and improve lives while also building the critical knowledge base needed for success in an era of scarce resources.”

The new funding comes with a new emphasis.

FPRC will work with the Florida Department of Health, Moffitt Cancer Center and various community partners to study the most effective ways to get underserved populations at high risk for colorectal cancer screened early for the disease.  Initially, they will identify people in Hillsborough, Pasco and Pinellas counties most likely to benefit from tests to help find colorectal polyps or cancer.

Moving forward the FPRC will apply its model to help understand and improve the cancer screening and follow-up system — from patients and healthcare practitioners to clinic administration and referral sources.

“We will look at the entire system at multiple levels to find potential barriers to care and identify changes that can make the system easier to use,” Bryant said.

That’s how Weeber, professor and chief scientific officer at the USF Health Byrd Alzheimer’s Institute, launched his TEDx presentation  “What We Know About the Human Brain.”  The May 15 talk was part of a series of short, powerful presentations intended to expose attendees to an eclectic mix of innovative ideas.

USF Health neuroscientist Edwin Weeber spoke at TEDx TampaBay 2014.

Weeber leads one of a handful of laboratories nationwide working to understand the molecular mechanisms underlying cognitive disruption in a mouse model for Angelman syndrome, a rare neurogenetic disorder affecting children. He is principal investigator for a recently completed clinical trial testing the effectiveness of the antibiotic minocycline in treating Angelman syndrome.

In his presentation, Weeber recalled the vivid experiences in his own life that helped shape a career focused on the neurobiology of learning and memory.

His beloved grandmother’s slow decline from early signs of memory loss — like burning cookies because she forgot to turn off the oven — to Alzheimer’s disease happened while he was away at college.

“I visited her when I was home from school, and she could not recognize me. That hurt and really affected me,” Weeber said. “Yet, I was struck by how her long-term memories of 50, 60 or 70 years ago remained intact.”

That experience prompted him to change his graduate studies from microbiology to neuroscience.  The more he learned about the brain, Weeber said, the more he realized that the brain’s potential to store information may be unlimited, or at least that its capacity is greater than we think.   He wondered if it might be possible to recover the processes underlying memory, even for a short time, in people with Alzheimer’s disease.

After receiving his PhD in neuroscience, he joined the laboratory of David Sweatt, PhD, a neuroscientist at Baylor University College of Medicine renowned for his multidisciplinary approach to studying learning and memory.  Meanwhile, down the hall from Sweatt’s laboratory, another scientific team identified the single gene defect causing Angelman syndrome and then disrupted that gene in a mouse to create a mouse model of human cognitive disorder.

Today, the genetically-altered Angelman syndrome mice mimic the same major symptoms seen in children with the disorder, including problems with memory and balance.

Mice, which share more than 90 percent of the genes found in people, make good models for studying the human brain, Weeber says.

As he worked with the Baylor mice models, Weeber discovered that he could reverse the neurological effects of Angelman syndrome by preventing the inhibition of CaMKII, an enzyme critically involved in the proper functioning of synapses and processes underlying learning and memory.

Along the way, he met a young girl with Angelman syndrome – an experience he says showed him the human side of the disease and “transformed the way” he thought about his research.

Ainsley exhibited the symptoms of the syndrome. Developmentally delayed, she had trouble walking and speaking, and suffered difficult-to-control seizures. But she was also mischievous, with an engaging sense of humor.

“In that way, she was a lot like my own child, but her parents faced day-to-day challenges difficult to comprehend,” Weeber said.

Since then, Weeber has connected with families across the world touched by Angelman syndrome.  The motivation to move his team’s scientific discoveries from lab to clinic took on a greater sense of urgency as parents shared their hopes for a cure or a first treatment to make the lives of their children better.

The preclinical work in Weeber’s Byrd Institute laboratory helped fast track minocycline as a drug candidate for one of the first clinical trials for Angelman syndrome.   Those trial results are expected to be published later this year.

“The internal rate of return for every dollar of NIH spending is 37 percent”  said Dr. Charles Lockwood, the new senior vice president for USF Health and dean of the Morsani College of Medicine. “I would invest all my money if I could achieve that kind of return.”

USF Health Senior Vice President Dr. Charles Lockwood commented on the economic benefits of federal research funding at the Biomedical Research Roundtable hosted by Moffitt Cancer Center and USF.

Dr. Lockwood’s point was one emphasized by several participants at the May 12 Biomedical Research Roundtable convened by the University of South Florida and Moffitt Cancer Center to highlight the importance of biomedical research to the Tampa Bay area.  The long-term benefits of robust federal research funding – sparking innovations that lead to longer lives, improved health and reduced disease and disability as well as spurring job creation and local economic growth — far outweigh its costs.

Dr. Lockwood spoke from the audience during the question-and-answer portion of the program, which featured panelists Dr. Alan List, Moffitt CEO; Dr. Thomas Sellers, center director at Moffitt; USF President Judy Genshaft; Dr. Paul Sanberg, senior vice president for research and innovation at USF; and three representatives from Florida’s Congressional delegation, U.S. Rep. Kathy Castor, U.S Rep. David Jolly and U.S. Rep. Dennis Ross.

Moderator John Schueler, chief operating officer of the Tampa Bay Partnership, called USF and Moffitt the anchors of biomedical research and development activities across the Tampa Bay region – fueling the discoveries and public-private partnerships that lead to intellectual property and new companies.

L to R:  Dr. Thomas Sellers, center director at Moffitt; Dr. Paul Sanberg, USF senior vice president for research and innovation; and USF President Judy Genshaft, were among the panelists at the roundtable discussion.

The clinicians, scientists, postdoctoral fellows, fellows and others attending expressed concern that the progress made by USF and Moffitt to help benefit patients with cancer and other diseases could be slowed if fiscal strains on NIH funding continue.

Federal funding for biomedical research has remained flat for more than a decade, outpaced by inflation, even as the need for upgrades in laboratory infrastructure and demands for a highly-trained scientific workforce grow. Grant applications have doubled yet fewer grants are funded, affecting both the number and dollar amounts of awards.

Dr. Lockwood pointed out that this downward trajectory disproportionately affects public research universities like USF, which last year received 61 percent of its $151 million in federally-funded grants from the NIH.

He suggested some ways to build upon the health and economic benefits driven by federally-supported biomedical advances and clinical breakthroughs and to remain competitive in a global research environment:

–          Tie federal research funding to the gross domestic product at a level comparable to investments by China, which is scaling up its research and development spending at a rate of growth projected to surpass the United States in the next few years.

–          Reassess the methods for determining the administrative overhead or “indirect” costs that are paid to universities by federal agencies as part of administering a grant.

–          Streamline regulations and critically evaluate and eliminate NIH extramural programs not proven to be cost-effective.

In addition to Dr. Lockwood, Dr. David Morgan, CEO of the USF Health Byrd Alzheimer’s Institute, and Dr. Aimee Klein, associate professor and coordinator of post-professional residency education at the USF School of Physical Therapy & Rehabilitation Sciences, were among the faculty members participating in the roundtable discussion.

L to R: Florida Congressional representatives,  David Jolly, Kathy Castor and Dennis Ross. The lawmakers listened to concerns by scientists, clinicians, and business and economic development leaders about the effects of declining federal  funding on the pace of research and development.

I expected to hear some interesting things about neuroscience related to brain disorders of aging, because that’s the expertise of Dr. Simpkins, director of the Center for Basic and Translational Stroke Research at West Virgina University.

I wasn’t disappointed.

USF Health Research Day 2014 speaker Dr. James Simpkins wove lessons he’s learned about
the politics of science into the discussion of his research on brain disorders of aging.

Dr. Simpkins recapped his years of preclinical research looking at estrogen’s capacity to protect against neurodegeneration – a course he stayed because the evidence was strong — even when news from the federally-funded Women’s Health Initiative (which did not initially report the trial findings stratified by age) created a commotion about the use of estrogen therapy in postmenopausal women.

He discussed the search for selective compounds containing estrogen that could protect nerve cells against diseases like Alzheimer’s or stroke without the risk of cancer associated with the use of estrogen. And he talked about his team’s latest study — investigating the molecular mechanisms that might help explain why a significant percentage of strokes are preceded by infections.

But, what I found even more interesting was the advice and observations he shared with the enthusiastic young student scientists in the room, gleaned from his career of, well, running against the wind.   Here’s a few lessons he says he’s learned about the politics of science along the way:

–          Associate with really smart people (smarter than you).

–          Your inspirations will come unexpectedly.

–          Scientific agendas set by bureaucrats are almost always bad.

–          The data are usually right and our biases are often wrong.

–          Your contribution to an area of research may be underappreciated or ignored (keep moving forward).

The kicker, though, was this:  “We are witnessing the decline of U.S biomedical research.”

Federal funding for biomedical research has remained flat since 2003, Dr, Simpkins said, which has ultimately slowed the pace of scientific advancement nationwide.

That means fewer NIH grants funded; fewer positions for faculty, postdoctoral fellows, and, in some places, even graduate students; and delays in infrastructure upgrades, he said.  “Part of the problem is that we don’t hang in the same circles as those who make decisions affecting biomedical research.”

Dr. Simpkins concluded by urging all the senior, junior and aspiring scientists in the audience to “tell the story of biomedical research and its struggle” to congressional representatives, legislative aides, potential donors and anyone else with the power to influence biomedical research policy and funding.

The story is not all glum.

At USF, there have been bright spots of sustained, even increased, research productivity.   University leaders point to our strong focus on translating science and technology from the laboratory to the marketplace along with USF’s strategic success in capturing more private and non-governmental grants and contracts while continuing to aggressively compete for federal and state research dollars.

Last year, USF moved up to 43^rd in the National Research Foundation’s ranking of research spending among both public and private universities – a 10-place improvement. The university attained a record $413.6 million in external research funding, more than half of which ($246 million) was generated by USF Health.

In her Research Day welcoming remarks, USF President Judy Genshaft recognized USF Health’s vital role in advancing the university’s research profile across the state, nation and globally.

Paul R. Sanberg, DSc, PhD, USF’s senior vice president for research & innovation, pointed to health sciences contributions leading to new inventions, startup companies and economic growth.  For instance, last year USF ranked 15th worldwide among universities producing new U.S. patents  – and 41 percent of the 76 new patents awarded to the university came from USF Health faculty members.  Also last year, USF Health technologies created a third of the startup companies spun off from the university.

“We looking forward to working with the new USF Health senior vice president, Dr. Charles Lockwood,” Dr. Sanberg said. “He’s a champion for commercialization of intellectual properties and public-private partnerships.”

So, my interest was piqued by the recent study testing whether a USF-developed antioxidant-rich nutritional supplement, called NT-020, which includes blueberries as one of its main ingredients, could improve the mental performance of healthy older adults.

httpv://www.youtube.com/watch?v=wcaOx28CjKg&feature=share&list=UUzZzLGbYx9OHlCjN5TTSv4w

The two-month trial randomized adults ages 65 to 85 to either a group receiving the supplement or a group getting a placebo pill; neither the researchers nor the study participants knew who was receiving the supplement. That was important in attributing any benefit observed in cognitive performance to the compound itself, rather than other factors like physical activity and mental exercises.

The supplement modestly improved measures of “cognitive processing speed.”  Those taking the NT-020 were able to more quickly complete tasks like matching identical patterns or comparing lists of multiple-digit numbers.  This information processing speed is one of the first cognitive functions to slip as we age, and it appears to underlie more complex cognitive functions like memory and verbal ability.

USF Health/VA neuroscientist Paula Bickford, PhD, teamed up with USF gerontologist Brent Small, PhD, to assess the NT-020 formula patented by USF in partnership with James A. Haley Veterans’ Hospital.

She believes the concentrated doses of antioxidants and other natural components in the supplement help reduce age-related damage to stem cells in the brain and can lead to an enriched environment for the neurons there, leading to better cognitive performance.

So, why can’t you just consume lots of blueberries, strawberries, green tea or whatever your favorite antioxidant-rich food happens to be to get the benefit shown in the trial?

“It’s the unique combination and interaction of certain ingredients in just the right amounts that is most potent in boosting the cells in the body important for brain health,” said Bickford, who uses rat models to study oxidative stress and inflammation in aging.

“Ultimately, we’re interested in finding ways that people, who are living longer, can maintain their cognitive health for as long as possible,” Small said.

The supplement may be another way to prevent or delay the age-related cognitive decline that eventually affects most Americans – but both Bickford and Small emphasize it’s not a substitute for obtaining nutrients from healthy foods.

Bickford uses the commercially available NT-020 supplement daily.  She also makes smoothies with blueberries, tosses fresh or frozen blueberries onto her spinach salads, and drinks plenty of green tea — another ingredient in the supplement, which also includes vitamin D3 and amino acids.

So, I’ll keep on eating lots of blueberries, because they’re delicious.  But, since I’m not getting any younger in a fast-paced world, I’m tempted to give the NT-020 a try.

 Video Editor: Klaus Herdocia, USF Health Communications

This approach to drug discovery is gaining momentum, in part, because developing a single new drug from scratch is estimated to cost as much as $800 million over a prolonged timeline of 10 to 17 years, says Dr. Zhou, professor and chair of the Department of Pharmaceutical Sciences at the USF College of Pharmacy.

All that time and expense may yield new drugs that demonstrate only minor changes in composition and aesthetics  – with little or no added benefit for patients, he adds.

So, pharmaceutical companies are looking to capitalize on their investments – by opening new markets for approved drugs, or revisiting shelved drug candidates as potential new medicines for both common and rare diseases.

                           Dr. Shu-Feng Zhou

One example of successful repositioning cited by Dr. Zhou is the infamous drug thalidomide (Thalomid), which resulted in thousands of babies with birth defects when it was used to treat morning sickness in pregnant women in the 1950s and early 60s. Following renewed research, the approved compound was returned to market in 2006 to treat the blood disorder multiple myeloma.

Read Dr. Zhou’s perspective on drug repositioning…

His work has included investigating how to harness stem cells produced by the body itself to repair or prevent brain damage. Because they originate in the person being treated, these “endogenous” stem cells are recognized as “self” by the immune system and unlikely to trigger a potentially harmful response.  If even small numbers could be coaxed to proliferate and honed to the damaged area of the brain, the benefit could be substantial.

Scientists doubt that endogenous stem cells alone can repair a sick or injured brain. A newly published study led by Dr. Borlongan bolsters evidence that indeed they cannot.

But the more compelling finding reported by his USF team was this:  Transplanted stem cells were critical to guide newborn stem cells arising in a particular part of the brain (known in scientific parlance as a neurogenic niche) to the injured site, promoting functional recovery in an animal model of traumatic brain injury.

In essence, Borlongan and colleagues present a new view of how transplanted stem cells mediate brain repair.

Cesar Borlongan, PhD

“I think our most intriguing observation was that stem cells are quite smart,” said Borlongan, who directs the USF Center for Aging and Brain Repair.

“The healthy and viable (transplanted) stem cells pave the way and form the biobridge that aids the journey of endogenous stem cells towards the injured brain tissue,” he said. “Most likely the (transplanted) cells were attracted to both a cell survival cue released by the neurogenic brain niche and the cell death signal released by the injured brain. In between these two survival and death depots, the stem cells build the biobridge.”

Once this “biobridge” is built, the hardworking transplanted cells appear to relinquish the task of carrying on repair to the brain’s host stem cells.

Previous studies have shown that even when millions of stem cells are transplanted into a sick or injured brain, only a few survive.

“Our biobridge observation provides a missing piece of the story about stem cell repair,” Borlongan said. “The transplanted stem cells actively work at night, clandestinely recruiting the new host cells, and by daytime when the biobridge is established, they disappear.”

The bone-marrow derived stem cells used in the USF study (SanBio Inc. SB632 cells) do not divide as prolifically as other types of stem cells or persist over time, so the risk of brain tumors or cancer following transplantation is highly unlikely, Borlongan notes.

A limited clinical trial to test the transplant of SB632 cells in patients with traumatic brain injury was recently approved by the Food and Drug Administration, based in part on the USF study

While the preclinical research is promising, Dr. Borlongan and others in the field of regenerative neuromedicine have plenty of challenging work ahead — from understanding the signaling cues needed to properly remodel the injured brain and finding drugs that may promote biobridge formation to identifying patient populations most likely to benefit from stem cell therapy.

When it comes to reproduction, women aren’t the only ones who may need to heed ticking biological clocks.

Newer studies, including one by researchers at the University of South Florida College of Public Health and the University of Rochester, suggest that the offspring of older men may face greater risks of harmful birth outcomes – attributed in part to age-related genetic defects passed along by the father’s sperm. Paternal lifestyle characteristics, like smoking and poor diets, and environmental toxins that lead to mounting epigenetic changes over time may also be part of the mix.

“In general, society has not talked about the age of the dad. The underlying thinking has been, since development occurs in the womb for nine months, that moms are the only ones who matter when it comes to pregnancy and birth outcomes,” said Hamisu Salihu, MD, PhD, professor of epidemiology and obstetrics at the USF College of Public Health. “But recent genetic and epidemiological research indicates that the father’s age may influence the processes of embryo development early in life.”

Dr. Salihu was quoted in the article “Too Old To Be a Dad?” appearing in the April 22, 2013 issue of Time magazine.

                                             Dr. Hamisu Salihu

 The Time piece cites a paper by Dr. Salihu and fellow investigators published last year in the American Journal of Men’s Health.

Analyzing more than 755,000 births in Missouri from 1989 to 2005, the researchers found that infants fathered by men in the 40-to-45 age group had a 24 percent greater risk of stillbirth than those fathered by men in the 25-to-29 category. Babies born to fathers older than age 45 were at 19 percent greater risk of low birth weight, 13 percent higher risk of preterm birth, and 29 percent increased risk of very preterm birth.

The exact chemical or physiological mechanisms to explain why advanced paternal age correlates with poorer birth outcomes are not yet known, Dr. Salihu says. But, he emphasized, the latest research points to the need for men to be included in preconception counseling and prenatal care to optimize the odds for a healthy baby.

“Now that we know the father’s age matters, it means we need screening protocols for older fathers, not just older mothers,” he says. “It’s going to change the paradigm of how we practice medicine.”

# # #