Called the Women’s Health Mini Residency Program, the sessions will help prepare VA health care teams who treat our nation’s women Veterans.

USF Health CAMLS (Center for Advanced Medical Learning and Simulation) was selected by the U.S. Department of Veterans Affairs to be the dedicated facility to host sessions that train VA health care providers from across the country who treat women veterans.

In the five-year agreement with the VA, CAMLS is hosting VA health providers up to twice yearly for training focused on breast and pelvic health, when more than 300 physicians, nurse practitioners and other health professionals travel to Tampa to tap into the expertise offered at CAMLS, including team training facilities, standardized patients and simulation training.

Called the Women’s Health Mini Residency Program, the effort is meant to bolster the expertise of the VA’s primary care health teams for a range of medical needs specific to women veterans.

In a press release sent out earlier this week, VA Secretary Robert Wilkie said: “More women Veterans are choosing VA for their health care than ever before. This mini residency program provides a unique learning opportunity for our clinical teams while addressing the extraordinary growth in VA services to women Veterans.”

Dr. Haru Okuda shares details about CAMLS and the Women’s Mini Residency Program with local reporters.

“We are proud that the VA has tapped into the expertise here at USF Health and at CAMLS for their efforts to enhance care for women veterans,” said Haru Okuda, MD, FACEP FSSH, executive director of USF Health CAMLS, executive director of USF Health Interprofessional Education and Practice, and professor in the Division of Emergency Medicine in the USF Health Morsani College of Medicine.

“For CAMLS, for USF Health, and for the greater Tampa Bay region, this is a significant achievement. We are now the national training site for incredibly important training for the coming five years, when health providers in VA medical facilities and clinics from across the country will train at USF Health CAMLS so they can return to their facilities to provide enhanced care for our increasing population of our nation’s women veterans.”

The number of women serving in the military is growing significantly, and a flagship training program is key in VA’s effort to have a workforce prepared to care for women Veterans, said Christine Kolehmainen, MD, director of Women’s Health Education, Women’s Health Services for the Office of Patient Care Services/Veteran Health Administration.

Dr. Christine Kolehmainen, director of VA Women’s Health Education, is interviewed about the Women’s Mini Residency Program hosted at CAMLS.

“Women veterans is the fastest growing veteran population in the VA and accounts for 30 percent of all newly enrolling Veterans,” Dr. Kolehmainen said. “Since 2001, women veterans seeking care within the VA has grown 200 percent from 160,000 to over 500,000 patients. The Women’s Health Mini Residency Program is part of VA’s continued effort to provide cutting-edge health care to the ever-increasing number of women Veterans seeking VA health care. The facilities at CAMLS, including their standardized patients, are invaluable to these trainings and are often cited on evaluations as the best part of the training.”

Central to the success of these training sessions are the standardized patients offered through CAMLS. Gynecologic teaching associates (GTAs) are specially trained standardized patients who helps facilitate medical scenarios during medical histories and examinations for these VA training sessions.

Barb Palmer, deputy field director for Women Health Services, describes the standardized patients used in the VA training.

“GTAs are such a critical component of this training,” said Barb Palmer, deputy field director for Women Health Services at the Veterans Affairs Central Office. “Their efforts contribute significantly to improving providers’ ability to perform or assist with a breast and pelvic exams and help them modify their approach in practice to completing pelvic exams for patients who have military sexual trauma.”

Central to the VA training sessions are standardized patients, offered through the USF Health Morsani College of Medicine. In an early practice session at CAMLS, Marcia Weller (center), meets Heather Rogers (right), a nurse practitioner, and Liane Marshall, a nurse, both with the Hershel Woody Williams VA Medical Center in Huntington WV. Photo by Allison Long.

Other scenes from the media event at CAMLS:

Rhea Law, chair of the Board of Directors for the USF Health Professions Conferencing Corp, which oversees CAMLS.

Dr. Susan Perry, vice dean for Faculty and Community Affairs, USF College of Nursing, and a retired Colonel from the U.S. Air Force., with Josh Harris, associate director of sales for Hilton Tampa Downtown.

Dr. Lisa Hardman, deputy director of VA Women’s Health Education, and Elizabeth Jackson, a veteran who shared details of her health care experience with a provider trained through the Women’s Mini Residency Program.

Photos by Freddie Coleman, USF Health Office of Communications.

His team searches beyond the hallmark Alzheimer’s disease proteins for alternative treatments

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In his laboratory at the USF Health Byrd Alzheimer’s Center, neuroscientist David Kang, PhD, focuses on how different types of proteins damage the brain when they accumulate there. In the case of Alzheimer’s disease, decades of good science has zeroed in on amyloid and tau, as the two types of hallmark proteins driving the disease process that ultimately kills brain cells.

Dr. Kang and his team investigate molecular pathways leading to the formation large, sticky amyloid plaques between brain cells, and to the tau neurofibrillary tangles inside brain cells –including the interplay between the two proteins. But, he is quick to point out that amyloid and tau are “not the full story” in the quest to understand how normally aging brains go bad.

“Our goal is to understand as much of the entire Alzheimer’s disease process as possible and then target specific molecules that are either overactive or underactive, which is part of the drug discovery program we’re working on,” said Dr. Kang, professor of molecular medicine and director of basic research for the Byrd Alzheimer’s Center, which anchors the USF Health Neuroscience Institute.

Neuroscientist David Kang, PhD, (third from left)  stands with his team in his laboratory at the Byrd Alzheimer’s Center, which anchors the USF Health Neuroscience Institute.

Attacking dementia from different angles 

Dr. Kang’s group takes a multifaceted approach to studying the biological brain changes that impair thinking and memory in people with Alzheimer’s, the most common type of dementia, as well as Lewy body, vascular and frontotemporal dementias.

That includes examining how damaged mitochondria, the energy-producing power plants of the cell, contribute to pathology in all neurodegenerative diseases. “Sick mitochondria leak a lot of toxins that do widespread damage to neurons and other cells,” Dr. Kang said.

Dr. Kang’s team was the first to identify how mutations of a gene, called CHCHD10, which contributes to both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), cause both mitochondrial dysfunction and protein pathology called TDP-43. Their findings on the newly identified mitochondrial link to both neurodegenerative diseases were published in Nature Communications in 2017.

The role of selective degradation in ridding cells of abnormal proteins, old or damaged organelles (including mitochondria) and other debris is another key line of research pursued by Dr. Kang and colleagues.

A single stained nerve cell | Microscopic image courtesy of Kang lab

“We believe something more fundamental is going wrong in the brain during the aging process to tip the balance toward Alzheimer’s disease – beyond what we call proteinopathy” or deposits of malformed proteins like toxic amyloid and tau, said Dr. Kang, whose work is bolstered by nearly $8 million in grant funding from the National Institutes of Health (NIH), the Veterans Administration (VA merit awards) and the Florida Department of Health.

“I think one of the fundamental things happening is that the (cellular) plumbing system isn’t working to clear out all the accumulating junk,” he said. “That’s why we’re looking at the protective clearance mechanisms (autophagy and mitophagy) that would normally quickly remove misfolded proteins and dysfunctional mitochondria.”

Unfortunately, pharmaceutical trials to date have yielded no effective treatments for Alzheimer’s disease, the sixth leading cause of death in the U.S.  Most clinical studies have centered on developing medications to block or destroy the amyloid protein plaque formation, and a few have targeted the tau-containing neurofibrillary tangles. The five Alzheimer’s drugs currently available may provide temporary relief of symptoms, such as memory loss and confusion. But, they do not prevent or delay the mind-robbing disease as toxic proteins continue to build up and dismantle the brain’s communication network.

Lesson learned: The critical importance of intervening earlier

Some scientists argue that the “amyloid hypothesis” approach is not working. Dr. Kang is among those who maintain that amyloid plays a key role in initiating the disease process that leads to brain atrophy in Alzheimer’s – but that amyloid accumulation happens very early, as much as 10 to 20 years before people experience memory problems or other signs of dementia.

Early detection and treatment are key, Dr. Kang says, because as protein plaques and other lesions continue to accumulate in the brain, reversing the damage may not be possible.

“One reason we’ve been disappointed in the clinical trials is because so far they have primarily targeted patients who are already symptomatic,” Dr. Kang said. “Over the last decade we’ve learned that by the time someone is diagnosed with early Alzheimer’s disease, or even mild cognitive impairment, the brain has degenerated a lot. And once those nerve cells are gone they do not, for the most part, regenerate… The amyloid cascade has run its course.”

As protein plaques and other lesions continue to accumulate, becoming apparent with MRI imaging, reversing the damage may not be possible.  So, for anti-amyloid therapies – or even those targeting downstream tau – to work, patients at risk of Alzheimer’s need to be identified and treated very early, Dr. Kang said.

USF Health is recruiting healthy older adults with no signs of memory problems for a few prevention trials. A pair of Generation Program studies will test the effectiveness of investigational anti-Alzheimer’s drugs on those at high genetic risk for the disease before symptoms start. And, the NIH-sponsored Preventing Alzheimer’s with Cognitive Training (PACT) study is examining whether a specific type of computerized brain training can reduce the risk of mild cognitive impairment and dementias like Alzheimer’s disease in those age 65 and older.

To accelerate early intervention initiatives, more definitive tests are needed to pinpoint biomarkers that will predict Alzheimer’s disease development in genetically susceptible people. Dr. Kang is hopeful about the prospects.  His own team investigates how exosomes, in particular the lipid vesicles that shuttle proteins and other molecules from the brain into the circulating bloodstream, might be isolated and used to detect people at risk of proteinopathy.

“I think within the next five years, some type of diagnostic blood test will be available that can accurately identify people with early Alzheimer’s brain pathology, but not yet experiencing symptoms,” he said.

Graduate research assistant Yan Yan, a member of Dr. Kang’s research team, works at a cell culture hood.

Searching for alternative treatment targets

Meanwhile, Dr. Kang’s laboratory continues searching for other treatment targets in addition to amyloid and tau — including the enzyme SSH1, which regulates the internal infrastructure of nerve cells, called the actin cytoskeleton. SSHI, also known as slingshot, is needed for amyloid activation of cofilin, a protein identified by the USF Health neuroscientists in a recent study published in Communications Biology as a possible early culprit in the tauopathy process.

“Cofilin is overactive in the brains of Alzheimer’s patients so if we can inhibit cofilin by targeting slingshot, it may lead to a promising treatment,” Dr. Kang said.

Ultimately, as with other complex chronic diseases, Alzheimer’s may not be eliminated by a single silver-bullet cure.  Rather, Dr. Kang said, a combination of approaches will likely be needed to successfully combat the neurodegenerative disorder, which afflicts 5.8 million Americans.

“I think prevention through healthy living is definitely key, because brain aging is modifiable based on things like your diet as well as physical activity and brain exercises,” he said.  “Also, we need to focus on earlier diagnosis, before people become symptomatic, and develop next-generation drugs that can attack the disease on multiple fronts.”

Xingyu Zhao, PhD, a research associate in the Department of Molecular Medicine, is among the scientists in Dr. Kang’s laboratory studying the basic biology of the aging brain.

Fascinated by how the brain works — and malfunctions

Dr. Kang came to USF Health in 2012 after nearly 20 years as a brain researcher at the University of California San Diego, where he earned M.S. and PhD degrees in neurosciences and completed NIH National Research Service Award fellowships in the neuroplasticity of aging.

As an undergraduate Dr. Kang switched from studying engineering to a dual major in science/psychology. He began focusing on neurosciences in graduate school, he said, because tackling how the brain works and malfunctions was fascinating and always challenged him.

“With every small step forward, we learn something else about the basic biology of the aging brain,” said Dr. Kang, “It’s not just helpful in discovering what therapeutic approaches may work best against Alzheimer’s disease – we’re also learning more about other neurodegenerative conditions affecting the brain.”

In addition to leading day-to-day research operations at the Byrd Center and helping to recruit new Alzheimer’s investigators, Dr. Kang holds the Mary and Louis Fleming Endowed Chair in Alzheimer’s Research and serves as a research neurobiologist at the James A. Haley Veterans Haley Veterans’ Hospital.

He has authored more than 50 peer-reviewed journal articles on brain aging and Alzheimer’s disease research. A member of the NIH Clinical Neuroscience and Neurodegeneration Study Section since 2016, he has served on multiple national and international editorial boards, scientific panels and advisory boards.

Dr. Kang sits next to a computer monitor depicting stained microscopic images — a single neuron (far left) and the two hallmark pathological proteins for Alzheimer’s disease, tau tangles (center) and amyloid plaques (right).

Some things you may not know about Dr. Kang

• His parents were Presbyterian missionaries in Africa, so he spent nine years of his early life (third through 10^th grade) in Nigeria.
• Dr. Kang practices intermittent fasting, often forgoing breakfast and eating only within an 8-hour window. Animal studies indicate the practice may contribute to lifespan and brain health by improving cellular repair through the process of autophagy, he said. “Autophagy really kicks your cells’ plumbing system into gear to clear out all the waste.”

-Video and photos by Allison Long, USF Health Communications and Marketing

Backed by a diverse research team, Jun Tan, MD, PhD, often takes the road less traveled when it comes to searching for new treatments for disorders affecting both the end and beginning of the lifespan:  Alzheimer’s disease and autism.

Dr. Tan, a professor of psychiatry, holds the Robert A. Silver Endowed Chair in Developmental Neurobiology at the USF Health Morsani College of Medicine.  His translational research laboratory, based at the Silver Child Development Center, is staffed by scientists whose expertise includes molecular biology, neuroscience, clinical neurology, animal models and behavioral analysis.

Supported by a new R21 grant from the National Institute on Aging, Dr. Jun Tan has been studying the therapeutic potential of a flavonoid found in the pulp and peel of citrus fruit (diosmin) in helping prevent and reduce Alzheimer’s disease pathology.

His knack for pursuing new approaches began in 1998, when he starting asking if Alzheimer’s disease could be linked with disorders of immunity.  This inquiry led Dr. Tan to focus on how amyloid beta (Aβ) peptide, which forms the sticky deposits in the brains of patients with Alzheimer’s, affects microglia, the resident immune cells of the brain.  He showed that Aβ activates microglia by increasing expression of a pro-inflammatory molecule, called CD40.  In addition, when microglia and nerve cells (neurons) were combined in a petri dish, treatment with Aβ caused neuronal injury by activating CD40.

It appears that when a switch (CD40) on the surface of microglia is turned “on,” these immune cells cease their usual defensive work.  They stop cleaning up the Ab protein that kills neurons. Instead, Dr. Tan explained, they begin to produce small proteins called cytokines, which damage neurons.  “Alzheimer’s disease is a trickster, able to harm and kill neurons using the brain’s own immune defenders,” Dr. Tan said.

Earlier studies by Dr. Tan and others, which generated worldwide response, established that delivering a vaccine transdermally, a method akin to a skin patch, could offer a potentially safe and effective treatment strategy for Alzheimer’s.

Dr. Tan and his team in one of their laboratories at the USF Health Silver Child Development Center.

Most recently, Dr. Tan has been studying the therapeutic potential of a flavonoid found in the pulp and peel of citrus fruit (diosmin) in helping prevent and reduce Alzheimer’s disease pathology (plaques and tangles) and curbing inflammation in the brains of mice genetically engineered to have the symptoms of the neurodegenerative disease.

With support from a new R21 grant from the NIH’s National Institute on Aging, Dr. Tan’s group will investigate the ability of oral diosmin to reduce memory impairment and other behavioral deficits in these mice – work that may lead to clinical trials testing diosmin dietary supplements in people at highest risk for Alzheimer’s or with mild cognitive impairment.  Their work is supplemented by a grant from the Florida Department of Health’s Ed and Ethel Moore Alzheimer’s Disease Research Program.

Other recent studies by Dr. Tan demonstrated that specific autoantibodies naturally occurring in aging individuals can promote production of amyloid plaques in the brains of mice.  His team was the first to show that certain autoantibodies drive Aβ peptide formation by altering the processing of its precursor, amyloid precursor protein or APP. Findings reported last year in Cell Death & Disease laid the groundwork for understanding why the prevalence of Alzheimer’s disease increases with age and may assist with development of amyloid-specific antibodies for treatment. The results may also be useful in creating a diagnostic test for determining Alzheimer’s risk at an early age based on specific autoantibody determinations.

Laboratory manager Huayan Hou with Dr. Tan.

“My staff are the ones who often come up with game-changing ideas and experimental approaches, driving the science,” Dr. Tan said.

For instance, Dr. Tan’s group discovered that the flavonoid EGCG, an extract of green tea, can inhibit the process that kills brain cells.  And, they recently demonstrated that the beneficial effects of EGCG may be due primarily to enhanced production of sAPPα, since restoring sAPPα levels can directly reduce the process that leads to Alzheimer’s-associated amyloid deposits (Journal of Neurochemistry, 2015).

Dr. Tan with magnified images (20x to 40x) of Alzheimer’s disease cell models.

Recent studies have shown that young whole blood as well as human umbilical cord blood cells may help rejuvenate aging tissues.  In light of these findings, Dr. Tan’s team recently showed that young blood may benefit aging individuals by helping to reduce Ab production and the accumulation of memory-choking amyloid plaques in the brains of Alzheimer’s mice. The USF researchers reported that young blood contributes to Aβ clearance by activating a novel APP-specific enzyme called a-secretase.  (Cell Transplantation, 2015 July 30).

“Discovering the factor in young blood that enhances APP-specific a-secretase processing holds great promise for treatment of Alzheimer’s disease,” Dr. Tan said.  “The known a-secretases in the brain that cleave APP are nonspecific, so stimulating them could generate unwanted side effects. But, the APP-specific a-secretase promoting activity has great potential therapeutic benefit since its product, sAPPα, promotes nerve cell development and survival.”

Dr. Tan has brought his expertise in immunity and inflammation in the adult brain to bear on disorders of brain development affecting children.  His team found significantly increased levels of sAPPα in the blood of 60 percent of children diagnosed with autism.  Based on this study, the USF researchers developed transgenic mice overexpressing human sAPPα in the brain. Then, they used the mouse model to demonstrate that this neural growth factor’s over-production alters brain growth and immune homeostasis, and plays a key role in producing autism-like pathology and impaired behavior in the mice.  Elevated blood levels of sAPPα could also be a potential biomarker for early autism diagnosis, Dr. Tan said.

“While sAPPα is an important neuroprotective agent in adults, overproduction of sAPPα also has its detrimental effects, particularly in the developing brain,” he said.

Brainstorming with colleagues, and critiquing each other’s ideas, is one of the key components in coming up with innovative and sound research proposals, Dr. Tan says. Here he chats with Darrell Sawmiller, PhD, senior research associate.

Over the past 20 years, Dr. Tan has authored more than 140 original scientific papers in prestigious national and international journals such as Science, Nature Neuroscience, Nature Medicine, Nature Commutations, EMBO J, PNAS, Journal of Neuroscience, Molecular Psychiatry and Acta Neuropathologica.  He has received grants and merit awards, totaling more than $13 million, from the National Institutes of Health, Veterans Administration and other peer-reviewed funding sources.

Dr. Tan’s philosophy is that everyone on his team has a strength, and the best way to lead is to combine those strengths to build a concerted effort toward success.

“Follow your dreams,” he advises the students in his laboratory.  “You can achieve great things if you believe.”

From left, Dr. Tan with postdoctoral student Yang Xiang, PhD, and Arsan Habib, PhD student.

Doug Shytle, PhD, (right) associate professor at the USF Center of Excellence for Aging and Brain Repair, is a co-investigator on Dr. Tan’s latest NIH grant studying the therapeutic potential of the flavonoid diosmin, found in grapefruit, oranges and other citrus, in fighting Alzheimer’s disease.

Photos by Eric Younghans, USF Health Communications and Marketing