Alzheimer's disease Archives - USF Health News

USF Health research team studying role that little-known protein plays in the riddle of Alzheimer’s disease

Admin — Wed, 14 Dec 2022 14:39:02 +0000

USF Health researchers are studying how a little-known protein known as BIN1 may contribute to the formation of tangles in the brain that are a hallmark of Alzheimer’s disease, a degenerative brain condition that affects more than 6 million Americans today.

Their findings have been published in the peer-reviewed Brain: A Journal of Neurology. Leading the study was Gopal Thinakaran, PhD, CEO of the USF Health Byrd Alzheimer’s Center and Research Institute and professor of molecular medicine in the USF Health Morsani College of Medicine. Contributing to the report were Moorthi Ponnusamy, PhD, and other members of the Thinakaran Lab at the Byrd Institute.

The paper focuses on a protein called Bridging Integrator 1 – or BIN1 – a protein that is found in cells in the brain and other organs. Understanding BIN1 has been a challenge because it appears in different forms in brain cells, but breakthroughs could lead to improved therapies for people who develop Alzheimer’s as they age.

“Aging is the leading risk factor for Alzheimer’s disease,’’ Dr. Thinakaran said. “A comparison of small changes in the DNA of people worldwide with and without Alzheimer’s disease found up to 40% carry small changes in the BIN1 gene, and many of those are at a higher risk for developing the disease.’’

Until recently, other proteins, such as beta amyloid and tau, which contribute to the formation of plaques and tangles in the brain, have received more attention from researchers. But now scientists are turning to risk factors such as BIN1, believing understanding their function might offer targets for potential treatments.

BIN1 is the second-most prevalent genetic risk factor identified for late-onset Alzheimer’s disease. It encodes an adaptor protein that regulates certain functions in the brain, and evidence suggests BIN1 can alter the dynamics of cell membranes within the brain.

Thinakaran’s team looked at whether the presence of BIN1 inside the brain’s neurons favors the accumulation of tau, a toxic protein, in structures called tangles. Greater numbers of these tangles in the brain have been associated with memory loss and the death of brain cells.

The team found that laboratory mice without BIN1 in their neurons developed only milder degeneration in the regions of the brain essential for memory. Also, brain inflammation was reduced by the loss of BIN1, suggesting that BIN1 in neurons also influences nerve, or glial, cell activation during the development of Alzheimer’s disease.

“These findings mean that BIN1 in neurons promotes Alzheimer’s disease tau pathology, stimulates brain inflammation, and contributes to memory loss, thus identifying BIN1 as a possible drug target,’’ Dr. Thinakaran said.

The timing of the team’s work is critical: The number of Americans affected is expected to rise to 13 million by 2050 and cost the United States more than $1 trillion, according to the Alzheimer’s Association, a global voluntary health organization dedicated to care, support and research.

Alzheimer’s is a specific brain disease that progressively and irreversibly destroys memory and thinking skills. Eventually, Alzheimer’s disease takes away the ability to carry out even the simplest tasks.

The vast majority of people who develop Alzheimer’s dementia are age 65 or older. Experts believe this late-onset Alzheimer’s, like other common chronic diseases, develops as a result of multiple factors rather than a single cause. Although a handful of laboratories worldwide are studying how BIN1 is involved in the disease process, Thinakaran’s team is leading the research efforts to define how BIN1 acts as a risk for Alzheimer’s disease in the elderly.

Their work is funded by three major research grants totaling $7 million from the National Institute on Aging, which is part of the National Institutes of Health, along with grants from the Cure Alzheimer’s Fund and the Alzheimer’s Association.

In June, the USF Health group published a related study in the journal Molecular Neurodegeneraton, which described BIN1’s impact on glial cells, which are responsible for brain inflammation.

— Story by Kurt Loft for USF Health News

USF Health Taneja College of Pharmacy students accepted into USF Connects cohort for their innovative health startup

Ryan Rossy — Wed, 02 Nov 2022 14:17:22 +0000

USF Connect – Student Innovation Incubator Orientation.

Two students in the USF Health Taneja College of Pharmacy (TCOP) launched a company that may have the newest innovation in diagnosing Alzheimer’s disease, and their work opened the way for acceptance to USF Connect, the university’s premier technology and design incubator.

TCOP pharmaceutical doctoral students Siegrid Pregartner and Laura Borgerding founded Janus AI (Artificial Intelligence), which designed a tool that aims to aid in the early detection of Alzheimer’s using AI technology.

The goal of their company is to give patients with Alzheimer’s disease the opportunity to take control of their lives and make the best healthcare decisions they can before the disease progresses too far.

“There are treatments coming out every single month for Alzheimer’s disease and the amount of money for research increases every single year but, we still do not have a way to know who does and who does not have the disease before symptom onset. Our tool will be able to diagnose patients for when more effective treatments come out to give people extra years to their lives when they are comfortable and in control,” said Pregartner.

USF Connect – The Business Incubator Program.

Recently, their health care startup company won first place and $15,000 at the Florida Blue Health Innovative Challenge, and has been accepted into USF Connects cohort.

“Winning the challenge will not only help us to develop our business but, also it made us realize that this could be a genuine business that could change lives,” Pregartner said.

Students who join a cohort through the USF Connect Incubator will be able to gain access to an abundance of resources such as business experts, legal, and investors. That will assist them in growing their business, concept, and product.

“USF Connect is going to help build a cohesive model and connect us with mentors that will help us with the implementation of our prototype and how to move forward as a business,” Borgerding said.

By utilizing their artificial intelligence tool, they could also contribute to further research and prove that certain drugs have a preventative effect on Alzheimer’s.

“Having the dean and our professors support us from the start at The USF Health Taneja College of Pharmacy, has been more than them just doing their job… that is them caring about our future and I think that has been the most important factor in our success,” Borgerding said.

(Left to right): Siegrid Pregartner and Laura Borgerding

Story and photos by Ryan Rossy, USF Health Communications and Marketing

“If we can reduce the chances of progressing to Alzheimer’s disease and related dementias with a cognitive training regimen – an inexpensive and safe non-drug intervention – that would be a huge public health advance,” Dr. Edwards said. “Research suggests that delaying the onset of dementia by even one year would result in millions of fewer cases over the next 30 years.”

Jerri Edwards, PhD, professor of psychiatry and behavioral neurosciences at the USF Health Morsani College of Medicine, is USF site principal investigator for the PACT study.

The multisite trial is expected to expand the study to enroll 7,600 healthy adults at various US locations who are ages 65 and older with no signs of cognitive impairment or dementia. People with mild cognitive impairment experience more memory problems than expected for those the same age. MCI can increase the risk for dementia. Within two years, Dr. Edwards said, about 15% of people with MCI progress to dementia with more serious cognitive decline that interferes with everyday tasks, such as preparing a meal, doing laundry, or driving.

Published research by Dr. Edwards and others indicates that targeted computerized training can help maintain mental and physical function. In the breakthrough Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, healthy older adults randomized to receive such training had a 29% lower risk of dementia after 10 years than the untreated control group. Those completing additional training benefited even more; they were 48% less likely to show signs of dementia 10 years later.

“As an academic medical center with a growing Neuroscience Institute and well-established Byrd Alzheimer’s Center, USF Health is at the forefront of the latest research attacking Alzheimer’s disease and related dementias on multiple fronts,” said Charles J. Lockwood, MD, senior vice president of USF Health and dean of the USF Health Morsani College of Medicine. “This pivotal study, based on compelling preliminary evidence, moves us one step closer to answering a critical question: Can computer-based cognitive training prevent dementia and help keep our brains healthy as we age?”

With the PACT study, Dr. Edwards’ team seeks more conclusive evidence about whether and how computerized training can protect against age-related cognitive impairment and dementia. The researchers will identify through comprehensive medical evaluation any study participants who develop MCI or dementia three years after enrollment in the PACT study. They will use brain scans to diagnose dementia such as Alzheimer’s disease and to see if those with amyloid protein in the brain (a hallmark protein of the neurodegenerative disease) benefit from the training.

Dr. Edwards emphasizes the need for more African-American and Hispanic/Latino study volunteers as the Alzheimer’s Association reports they are populations at highest risk for Alzheimer’s disease and other dementias.

USF Health expects to continue enrolling participants across the Tampa Bay region in the PACT study over the next three years. Study participants cannot have dementia or other neurological disorders, but a family history of Alzheimer’s disease does not disqualify an otherwise healthy person. Two initial supervised training sessions will be conducted onsite (with strict adherence to CDC guidelines for COVID-19), and study participants will complete the remaining brain training sessions independently at home over the next two years.

For more information, please visit the PACT study website at pactstudy.org or call (813) 974-6703.

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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 Taneja College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and USF Health’s multispecialty physicians group. The University of South Florida is a high-impact global research university dedicated to student success. Over the past 10 years, no other public university in the country has risen faster in U.S. News & World Report’s national university rankings than USF. For more information, visit health.usf.edu

New vaccine targeting toxic amyloid-β could help halt Alzheimer’s disease progression, preclinical study finds

Anne DeLotto Baier — Tue, 20 Oct 2020 13:22:02 +0000

University of South Florida Health neuroscientist suggests the therapeutic immunomodulatory vaccine may be safer for those with age-associated decline in immunity

In the Alzheimer’s disease brain, the amyloid beta peptide clumps together to form hardened plaques between nerve cells.

TAMPA, Fla (Oct. 20, 2020) — Our immune system’s capacity to mount a well-regulated defense against foreign substances, including toxins, weakens with age and makes vaccines less effective in people over age 65. At the same time, research has shown that immunotherapy targeting neurotoxic forms of the peptide amyloid beta (oligomeric Aβ) may halt the progression of Alzheimer’s disease, the most common age-related neurodegenerative disease.

A team led by Chuanhai Cao, PhD, of the University of South Florida Health (USF Health), has focused on overcoming, in those with impaired immunity, excess inflammation and other complications that interfere with development of a therapeutic Alzheimer’s vaccine.

Now, a preclinical study by Dr. Cao and colleagues indicates that an antigen-presenting dendritic vaccine with a specific antibody response to oligomeric Aβ may be safer and offer clinical benefit in treating Alzheimer’s disease. The vaccine, called E22W42 DC, uses immune cells known as dendritic cells (DC) loaded with a modified Aβ peptide as the antigen.

The Alzheimer’s mouse model study of this new investigational vaccine was published early online Oct. 13 in the Journal of Alzheimer’s Disease.

One of the two hallmark pathologies of Alzheimer’s disease is hardened deposits of Aβ that clump together between nerve cells (amyloid protein plaques) in the brain; the other is neurofibrillary tangles of tau protein inside brain cells. Both lead to damaged neurological cell signaling, ultimately causing the onset of Alzheimer’s disease and symptoms.

“This therapeutic vaccine uses the body’s own immune cells to target the toxic Aβ molecules that accumulate harmfully in the brain,” said principal investigator Dr. Cao, a neuroscientist at the USF Health Taneja College of Pharmacy, USF Health Morsani College of Medicine and the university’s Byrd Alzheimer’s Center. “And, importantly, it provides strong immunomodulatory effects without inducing an unwanted, vaccine-associated autoimmune reaction in the aging mice.”

Unfortunately, clinical trials of all anti-amyloid treatments for Alzheimer’s disease so far have failed – including the initial vaccine trial targeting Aβ (AN-1792), which was suspended in 2002 after several immunized patients developed central nervous system inflammation. “Inflammation is a primary symptom of Alzheimer’s disease, so any possible treatment which has neural inflammation as a side effect essentially pours gas on the fire,” Dr. Cao said.

A next-generation anti-amyloid vaccine for Alzheimer’s would ideally produce long-lasting, moderate antibody levels needed to prevent Aβ oligomers from further aggregating into destructive Alzheimer’s plaques, without over-stimulating the immune systems of elderly people, Dr. Cao added.

In this study, the researchers tested the vaccine they formulated using modified Aβ-sensitized dendritic cells derived from mouse bone marrow. Dendritic cells interact with other immune cells (T-cells and B-cells) to help regulate immunity, including suppressing harmful responses against healthy tissues. “Because we use dendritic cells to generate antibodies, this vaccine can coordinate both innate and acquired immunity to potentially overcome age-related impairments of the immune system,” Dr. Cao said.

USF Health neuroscientist Chuanhai Cao, PhD, led the preclinical study testing a novel therapeutic Alzheimer’s vaccine.

The study included three groups of transgenic (APP/PS1) mice genetically engineered to develop high levels of Aβ and behavioral/cognitive abnormalities that mimic human Alzheimer’s disease. One group was vaccinated with the investigational E22W42 DC vaccine, another received an endogenous amyloid beta peptide to stimulate dendritic cells (wild-type vaccine group), and the third was injected with dendritic cells only, containing no Aβ peptide (DC control group). A fourth group was comprised of untreated healthy, older mice (nontransgenic control group).

Among the study findings:

– The vaccine slowed memory impairment in the Alzheimer’s transgenic mice, with mice in the E22W42 DC vaccinated group demonstrating memory performance similar to that of the nontransgenic, untreated mice. In a cognitive test called a radial arm water maze, the E22W42 DC-vaccinated mice also showed significantly less errors in working memory than the mice injected with non-sensitized dendritic cells only (DC controls). Loss of working memory makes it difficult to learn and retain new information, a characteristic of Alzheimer’s disease.

– No significant differences were found in the quantities of inflammatory cytokines measured in the plasma of the vaccinated mice, versus amounts in the control mice. The researchers concluded that the E22W42 DC vaccine has “little potential for over priming the immune system.”

– E22W42 DC-vaccinated mice showed higher levels of anti-Aβ antibodies in both in their brain and in their blood than the transgenic control mice administered dendritic cells containing no modified Aβ peptide.

– Only Aβ peptides with mutations introduced in the T-cell epitope (the distinct surface region of the antigen where complementary antibodies bind) can sensitize the dendritic cells to target toxic oligomeric forms of Aβ, the researchers reported. A major advantage of E22W42 is that the antigen can stimulate a specific T-cell response that activates the immune system and silence some T-cell epitopes associated with an autoimmune response, they added.

“Though the E22W42-sensitized DC vaccine is being developed for patients with Alzheimer’s disease, it can potentially help strengthen the immune system of elderly patients (with other age-related disorders) as well,” the study authors concluded.

Dr. Cao conducted the study with collaborators from Tianjin University of Traditional Chinese Medicine and Michigan State University. The team’s research was supported by grants from the National Institutes of Health, Florida High Tech Corridor matching funds, and MegaNano Biotech Inc. The University of South Florida holds a patent related to E22W42 DC vaccine technology.

Research Day speaker shares insights on the race to cure Alzheimer’s disease

Anne DeLotto Baier — Mon, 24 Feb 2020 14:07:49 +0000

USF Health Research Day 2020 keynote speaker Allan Levey, MD, PhD, spoke about some of his work with national collaborators from various disciplines. He directs Emory University School of Medicine’s Goizueta Alzheimer’s Disease Research Center, one of 32 NIH-funded ADRCs in the U.S.

Alzheimer’s disease, affecting as many as one out of every two people over age 85, is an impending epidemic in the U.S., where the rate of people living into their 80s and beyond continues to rise.

Despite the failure of pharmaceutical trials to yield any treatments to halt or delay the devastating brain degeneration of this complex, chronic disease, Allan Levey, MD, PhD, this year’s Research Day keynote speaker, encouraged the audience of experienced and emerging USF Health scientists to remain optimistic.

“Now more than ever is the time to invest in research. We have powerful new tools and interdisciplinary approaches that are helping us discover more about the root causes of Alzheimer’s disease and related dementias,” said Dr. Levey, professor and chairman of neurology at Emory University School of Medicine and director of Emory’s Alzheimer’s Disease Research Center. “So, there is great reason for hope, but we need to wake up the country about the looming crisis.”

Dr. Levey, a practicing neurologist and widely respected neuroscientist, shared his perspectives on the race to cure Alzheimer’s disease as well some data from his own work at Emory and with national collaborators. He co-leads a National Institutes of Health-funded, multi-institutional Open Drug Discovery Center for Alzheimer’s Disease dedicated to advancing and diversifying the pipeline for innovative therapeutics. He also co-chairs an advisory council of the U.S. Department of Health and Human Services’ National Alzheimer’s Project Act Plan, which ambitiously lists as its top goal to “prevent and effectively treat Alzheimer’s disease and related dementia by 2025.”

Deanna Chan, Department of Molecular Pharmacology and Physiology, discusses her neuroscience research poster with Dr. Levey.

Dr. Levy commended the work of USF Health faculty and trainees at the Byrd Alzheimer’s Center, who are embracing new approaches to better understand the underlying causes of Alzheimer’s disease and related neurodegenerative disorders, and to translate those discoveries into urgently needed, effective treatments.

“If you have a foundation of outstanding clinical care like you have here, that becomes a basis for a number of (regional and national) collaborative research opportunities,” he said. “There are huge opportunities for you to make a difference.”

Some highlights from Dr. Levey’s presentation follow:

Alzheimer’s disease and related disorders belong to a broad family of overlapping neurodegenerative diseases including Lewy body, vascular, and frontotemporal dementias. Studies of postmortem brains show that it’s “extraordinarily rare” for an individual with Alzheimer’s disease to have only the hallmark features of amyloid plaques and neurofibrillary tau tangles, Dr. Levey said. “Alzheimer’s is almost always accompanied by other co-existing pathologies.” Some brain changes shared with Alzheimer’s include alpha-synuclein pathology (present in Lewy body dementia and Parkinson’s disease) and TDP-43 (also found in frontotemporal dementia and ALS).
Underlying damage to the brain typically builds for 15-20 years before the first symptoms of cognitive decline, like problems with thinking and memory, appear. That presents a major challenge requiring low-cost, noninvasive biomarkers (substances that indicate the presence of disease) to better understand specifically how Alzheimer’s progresses and to help predict the disease’s onset early and what type of treatments are more likely to work. Dr. Levey works with a company developing a simple eye test to visualize accumulating amyloid protein deposits in the retina. And, currently under review is the first potential blood test to measure very low levels of amyloid in the circulation. “We need to intervene before the (brain) degeneration occurs,” he said. “I’m very confident that we’re going to have dramatic advances in detection and diagnosis capabilities over the next year or two, and that would be a game changer.”
For nearly 20 years, clinical trials mostly focused on developing Alzheimer’s medications and vaccines to block or destroy amyloid plaque formation – without clear success. “What we’ve learned, slowly and painfully, is that we can remove amyloid from the brains of individuals with mild-to-moderate Alzheimer’s disease without changing the progression of dementia,” he said. Now, armed with new genomic and proteomic technologies, researchers are looking for additional molecular and cellular pathways (implicated in inflammation, membrane trafficking, synaptic trafficking, to name a few), which may identify new treatment targets, beside amyloid and tau.
Some people with genetic risk factors never get Alzheimer’s disease. So, researchers have begun to amass and analyze large amounts of data on modifiable environmental/lifestyle factors — including diet, physical and mental exercise, and cardiovascular risk factors like cholesterol, high blood pressure, and diabetes. What they learn could help keep the brain healthy and stave off cognitive decline in high-risk individuals as they age. Identifying and treating even a third of the (modifiable) risk factors “could have a huge public health impact,” Dr. Levey said.
Over 200 proteins have been nominated as potential new treatment targets through the NIH’s Accelerating Medicines Partnership-Alzheimer’s Disease. Levey leads one AMD-AD multi-institutional project focused on discovering and validating novel proteomic targets. The researchers apply the latest systems and network biology approaches to integrate proteomic data from donated postmortem human brains (healthy and at various stages of disease). They’ve identified groups of proteins associated with inflammation, and expressed at higher levels in people as cognitive impairment increases, which appear promising as targets for treating early-stage Alzheimer’s disease.

Dr. Levey with Stephen Liggett, MD, USF Health associate vice president for research and senior vice president for research at the Morsani College of Medicine

Dr. Levey also described a clinical trial he recently completed at Emory to test in patients with mild cognitive impairment the effects of atomoxetine, a selective norepinephrine transport inhibitor FDA approved to treat attention deficit disorder. The study results proved encouraging enough to begin designing a larger multiphase drug trial, he said.

-Photos by Freddie Coleman, USF Health Communications and Marketing

USF Health celebrates 30th Research Day with record number of poster submissions

toriedoll — Fri, 21 Feb 2020 21:52:50 +0000

The familiar sea of colorful research posters decorated the USF Tampa campus Marshall Student Center ballroom on the morning of Feb. 21. USF Health Research Day 2020 marked 30 years of showcasing the best interdisciplinary scholarly research from students, faculty and staff across all health disciplines.

USF Health Research Day 2020 marked 30 years of showcasing the best interdisciplinary scholarly research from across all health disciplines.

More than 340 poster presentations out of over 400 submissions were on display representing the profound span of research conducted within the colleges of Medicine, Nursing, Public Health and Pharmacy, as well as health-related collaborations with other USF colleges and several hospital affiliates. Research Day is the largest interdisciplinary research event at the University of South Florida, and both spotlights existing collaborations and encourages the formation of new ones.

Presentations ranged from pilot, preliminary, empirical and case studies to systemic reviews and reviews of literature or charts.

Yingwei Yang, doctoral student at the College of Public Health and one of the 12 Joseph Krzanowski Invited Oral Presenters, explains her poster presentation on the co-occurring impact of individual and community risk factors on youth’s perceived safety.

Stephen Liggett, MD, associate vice president for research at USF Health, welcomes attendees to Research Day 2020.

Stephen Liggett, MD, associate vice president for research at USF Health, described the poster presentation room as a “beehive” of activity and said, “the energy that you feel during Research Day is contagious. The enthusiasm that researchers have for their own work creates a special environment.”

The Roy H. Behnke keynote speaker was Allan Levey, MD, PhD, Betty Gage Holland Professor and Chair, Department of Neurology, Emory University, and Director, Emory Alzheimer’s Disease Research Center. Dr. Levey presented, “Racing to a Cure for Alzheimer’s Disease.” Dr. Levey was excited to participate in USF Health’s Research Day, saying that Emory University does not currently have an event like it.

Deanna Chan discusses her poster presentation with keynote speaker, Allan Levey, MD, PhD.

The Roy H. Behnke keynote speaker was Allan Levey, MD, PhD, who presented on his Alzheimer’s disease research.

Dr. Levey is a neurologist and neuroscientist internationally recognized for his work in neurodegenerative disease. He has more than 270 research publications. His work has contributed to understanding the brain systems and mechanisms involved in neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, and in identifying molecular targets for new therapeutic strategies.

Dr. Levey thinks about his passion for Alzheimer’s research at every graduation he attends. “If we don’t do something quickly, 1 out of every 2 of those graduates is going to develop Alzheimer’s disease,” Dr. Levey said.

The goal in the USA National Plan is to prevent and effectively treat Alzheimer’s disease by 2025. Dr. Levey urges interdisciplinary collaboration because he believes that what’s needed for Alzheimer’s research is “people from other fields to join and bring fresh ideas.”

Jasmine Carter and Miranda E. Essa, research assistants in the College of Nursing, set up their poster presentation on the adaption of a web-based intervention system specifically for firefighters and first responders.

Jasmine Carter and Miranda E. Essa, research assistants in the College of Nursing and recent USF graduates of psychology, were part of a team of seven whose research focused on tailored messages aimed towards firefighters for the web-based Tailored Intervention Messaging System (TIMS©). TIMS© is an existing intervention designed to increase cancer screening behavior, and the goal of Jasmine and Miranda’s study was to gather information specifically on firefighters to inform the adaption of this web-based intervention system. The chances of getting colorectal cancer, one of the most preventable of all cancers, is very high in a firefighter and first responder’s environment.

“Firefighters risk their lives for others, but it’s also important that they take care of themselves and get screened for colorectal cancer,” Carter said.

This presentation of research was a culmination of eight months of qualitative work into the risks and barriers for why firefighters and first responders often don’t receive annual colorectal screenings. Essa joined Carter at USF Health Research Day 2020 and was excited to see their research come together in a display.

“We are so excited and hyped to show off all this hard work we’ve been doing for the past eight months and to be able to explain it to people,” Essa said. “This is one of the few cancers you can genuinely prevent, so I think it’s really important information to get out there to everyone.”

Charles Lockwood, MD, MHCM, dean of the Morsani College of Medicine and senior vice president of USF Health, learns about Salma S. Abdelmaboud’s team’s research on sigma-1 receptors.

Salma S. Abdelmaboud, a research assistant in the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, presented research on the protective effects of the sigma-1 receptor on lymphatic endothelial cells. The study aimed to test the role of sigma-1 in lymphatic endothelial barrier function and explore its influence in lymphatic endothelial bioenergetics. Collectively, the results suggest that sigma-1 might serve as a potential future therapeutic target for the lymphatic system.

“This was my first time presenting my poster,” Abdelmaboud said. “Dr. Lockwood was the first person I presented my poster to, and I’m so happy that the dean liked what I did.” Abdelmaboud is applying for her PhD and is excited about her interview next week.

Byron Cheon, second-year medical student and one of the 12 Joseph Krzanowski Invited Oral Presenters, explains his poster presentation, “Open Data: Novel Uses and Old Ethical Concerns New Again.”

Tampa General Hospital, the primary teaching hospital for USF Health Morsani College of Medicine, ResearchOne and the USF Federal Credit Union, were the sponsors for USF Health Research Day 2020.

After attendees and the 124 volunteer judges had the chance to buzz around all the poster presentations and interact with the participants, the 11th Annual Joseph Krzanowski Invited Oral Presenters took their research to the Oval Theatre stage. Out of the 12 presenters, Kristi Miley, doctoral student, College of Public Health, won the Outstanding Oral Presentation Award for her presentation titled “Evaluation of Eastern Equine Encephalitis Virus (EEEV) Winter Activity in Florida.”

Kristi Miley (center), doctoral student, College of Public Health, won the Joseph Krzanowski, PhD Invited Oral Presentations Award. The USF Health Research Day TGH Presenting Sponsor Awards were presented by Sally H. Houston, MD (right), executive vice president and chief medical officer, and Matthew L. Anderson, MD, PhD (left), director of gynecologic oncology research.

The day-long celebration of research concluded with a ceremony announcing top award and certificate winners:

The Best Poster in the Field of:
- Cardiovascular Biology
  - Julia Fedorova
- Immunology and Microbiology
  - Ojas Natarajan
- Molecular and Cellular Biology
  - Dante Deascanis
- Neuroscience
  - Yan Yan
- Other Clinical Research
  - Andrew Sephien
- Nursing
  - Dorothie Durosier Mertilus
- Other Basic Research
  - Olivia Hardy

Medical Student Research:
- Year 1, 2 (Basic Science)
  - Vineet Nadkarni
- Year 1, 2 (Clinical / Translational Science)
  - John Cheng
- Year 3, 4
  - Alexander Shahin
- Case Study / Review Award
  - Zachary Makovich

Student Basic Sciences:
- Doctoral Student Research
  - Helena Hernandez-Cuervo
- COPH Doctoral Student Research
  - Nisha Vijayakumar
- Masters Student Research
  - Mitchell Farmer
- COPH Masters Student Research
  - Jan Dahrendorff
- Undergraduate Student Research
  - Alexander Llauget

Student Clinical / Translational Sciences:
- Doctoral Student Research
  - Alexandra Cochrane
- COPH Doctoral Student Research
  - Kenneth Taylor
- Masters Student Research
  - Amrita Unnikumaran
- COPH Masters Student Research
  - Emma Hume
- Undergraduate Student Research
  - Aizara Ermekbaeva

Post-Doctoral Scholar Research Award
- Jea-Young Lee

The Community Research Award (COPH):
- Doctoral Student Research
  - Marshara Fross
- Masters Student Research
  - Davies Toluhi

The USF Health Dean’s Interdisciplinary Research Award
- Caitlin Wolfe

The Outstanding Innovations in Medicine Award
- Zeinab Motawe

The Outstanding 4th Year Medical Student Poster Award (Presented by Watson Clinic)
- Yumna Ahmad

The Dr. Christopher P. Phelps Memorial Fund Annual Morsani College of Medicine Neuroscience Student Travel Award
- Sara Cazzaro

The USF Federal Credit Union Best Poster in the Field of Cancer Biology Award
- Roukiah Khalil

The Tampa General Hospital Travel Award for Clinical Fellows
- David Gajzer

The Tampa General Hospital Outstanding Medical Resident Research Award
- Evelena Cousin-Peterson

The Joseph Krzanowski, PhD Invited Oral Presentations Award
- Kristi Miley

USF bulls pride from the Research Day 2020 award winners.

More highlights from Research Day 2020

-Photos by Freddie Coleman and video by Allison Long, USF Health Communications and Research

Beta-arrestin2 increases neurotoxic tau driving frontotemporal dementia

Anne DeLotto Baier — Mon, 17 Feb 2020 20:00:56 +0000

University of South Florida study suggests a new approach to inhibit the buildup of brain-damaging tau tangles associated with FTLD, Alzheimer’s disease and related dementias

TAMPA, Fla. (Feb. 18, 2020) — The protein β-arrestin2 increases the accumulation of neurotoxic tau tangles, a cause of several forms of dementia, by interfering with removal of excess tau from the brain, a new study by the University of South Florida Health (USF Health) Morsani College of Medicine found.

A beta-arrestin2 oligomer (foreground) shown within a nerve cell (background). Oligomerized beta-arrestin2 plays a central role in impairing tau clearance and the development of tau aggregates (magenta) in frontotemporal lobe degeneration and Alzheimer’s disease. | Image courtesy of artist Cynthia Greco and Eric Lewandowski (beta-arrestin2 protein modeling)

The USF Health researchers discovered that a form of the protein comprised of multiple β-arrestin2 molecules, known as oligomerized β-arrestin2, disrupts the protective clearance process normally ridding cells of malformed proteins like disease-causing tau. Monomeric β-arrestin2, the protein’s single-molecule form, does not impair this cellular toxic waste disposal process known as autophagy.

Their findings were first published Feb. 18 in the Proceedings of the National Academy of Science (PNAS).

The study focused on frontotemporal lobar degeneration (FTLD), also called frontotemporal dementia — second only to Alzheimer’s disease as the leading cause of dementia. This aggressive, typically earlier onset dementia (ages 45-65) is characterized by atrophy of the front or side regions of the brain, or both. Like Alzheimer’s disease, FTLD displays an accumulation of tau, and has no specific treatment or cure.

“Our research could lead to a new strategy to block tau pathology in FTLD, Alzheimer’s disease and other related dementias, which ultimately destroys cognitive abilities such as reasoning, behavior, language, and memory,” said the paper’s lead author JungA (Alexa) Woo, PhD, an assistant professor of molecular pharmacology and physiology and an investigator at the USF Health Byrd Alzheimer’s Center.

“It has always been puzzling why the brain cannot clear accumulating tau” said Stephen B. Liggett, MD, senior author and professor of medicine and medical engineering at the USF Health Morsani College of Medicine. “It appears that an ‘incidental interaction’ between β-arrestin2 and the tau clearance mechanism occurs, leading to these dementias. β-arrestin2 itself is not harmful, but this unanticipated interplay appears to be the basis for this mystery.”

The USF Health research team included, from left: Stephen Liggett, MD, senior author; David Kang, PhD, coauthor; and JungA (Alexa) Woo, PhD, lead author. | Photo by Freddie Coleman

“This study identifies beta-arrestin2 as a key culprit in the progressive accumulation of tau in brains of dementia patients,” said coauthor David Kang, PhD, professor of molecular medicine and director of basic research for the Byrd Alzheimer’s Center. “It also clearly illustrates an innovative proof-of-concept strategy to therapeutically reduce pathological tau by specifically targeting beta-arrestin oligomerization.”

The two primary hallmarks of Alzheimer’s disease are clumps of sticky amyloid-beta (Aβ) protein fragments known as amyloid plaques and neuron-choking tangles of a protein called tau. Abnormal accumulations of both proteins are needed to drive the death of brain cells, or neurons, in Alzheimer’s, although the tau accumulations now appear to correlate better with cognitive dysfunction than Aβ, and drugs targeting Ab have been disappointing as a treatment. Aβ aggregation is absent in the FTLD brain, where the key feature of neurodegeneration appears to be excessive tau accumulation, known as tauopathy. The resulting neurofibrillary tangles — twisted fibers laden with tau — destroy synaptic communication between neurons, eventually killing the brain cells.

“Studying FTLD gave us that window to study a key feature of both types of dementias, without the confusion of any Aβ component,” Dr. Woo said.

Monomeric β-arrestin2 is mostly known for its ability to regulate receptors, molecules on the cell that are responsible for hormone and neurotransmitter signaling. β-arrestin2 can also form multiple interconnecting units, called oligomers. The function of β-arrestin2 oligomers is not well understood.

The monomeric form was the basis for the laboratory’s initial studies examining tau and its relationship with neurotransmission and receptors, “but we soon became transfixed on these oligomers of β-arrestin2,” Dr Woo said.

Neurofibrillary tangles laden with tau (stained red) destroy synaptic communication between neurons, eventually killing the brain cells. This tau pathology is a feature of frontotemporal dementia, Alzheimer’s disease and several other dementias. | Image courtesy of David Kang

Among the researchers’ findings reported in PNAS:

– Both in cells and in mice with elevated tau, β-arrestin2 levels are increased. Furthermore, when β-arrestin 2 is overexpressed, tau levels increase, suggesting a maladaptive feedback cycle that exacerbates disease-causing tau.

– Genetically reducing β-arrestin2 lessens tauopathy, synaptic dysfunction, and the loss of nerve cells and their connections in the brain. For this experiment researchers crossed a mouse model of early tauopathy with genetically modified mice in which the β–arrestin2 gene was inactivated, or knocked out.

– Oligomerized β-arrestin2 — but not the protein’s monomeric form – increases tau. The researchers blocked β-arrestin-2 molecules from binding together to create oligeromized forms of the protein. They demonstrated that pathogenic tau significantly decreased when β-arrestin2 oligomers are converted to monomers

– Oligomerized β-arrestin2 increases tau by impeding the ability of cargo protein p62 to help selectively degrade excess tau in the brain. In essence, this reduces the efficiency of the autophagy process needed to clear toxic tau, so tau “clogs up” the neurons.

– Blocking of β-arrestin2 oligomerization suppresses disease-causing tau in a mouse model that develops human tauopathy with signs of dementia.

Above: Control nerve cells (green), in which oligomerized beta-arrestin-2 contributes to the accumulation of disease-causing tau (magenta). Below: When the neurons are transduced with b-arrestin2 oligomerization blocking viruses, tau pathology is dramatically reduced. | Images appearing in PNAS (Fig 6D) courtesy of Alexa Woo

“We also noted that decreasing β-arrestin2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles like an eraser,” Dr. Liggett said. “This is something the field has been looking for — an intervention that does no harm and reverses the disease.”

“Based on our findings, the effects of inhibiting β-arrestin2 oligomerization would be expected to not only inhibit the development of new tau tangles, but also to clear existing tau accumulations due to the mechanism of enhancing tau clearance,” the paper’s authors conclude.

The work is consistent with a new treatment strategy that could be preventive for those at risk or with mild cognitive impairment, and also for those with overt dementias caused by tau, by decreasing the existing tau tangles.

The study was supported in part by grants from the National Institutes of Health, National Institute on Aging.

Get ready to celebrate scientific excellence at Research Day 2020

Anne DeLotto Baier — Thu, 13 Feb 2020 00:33:41 +0000

Physician-scientist Dr. Allan Levey of Emory University will share his perspective on “Racing to a Cure for Alzheimer’s Disease”

//www.youtube.com/watch?v=TwCV7ERPMTU

USF Health Research Day 2020 – Friday, Feb 21, in the USF Marshall Student Center — is right around the corner. The annual event showcases the best scientific work of students, residents, and postdoctoral scholars across all four USF Health colleges, as well as biomedical science-related collaborations with other USF colleges and several hospital affiliates.

Roy H. Behnke Keynote speaker Allan Levey, MD, PhD, professor and chair at Emory University’s Department of Neurology, will share his outlook on Racing to a Cure for Alzheimer’s Disease, beginning at 9 a.m. Dr. Levey, a neurologist and neuroscientist, is internationally recognized for his work in neurodegenerative diseases. He directs Emory’s Goizueta Alzheimer’s Disease Research Center and co-leads a National Institutes of Health-funded, multi-institutional Open Drug Discovery Center for Alzheimer’s Disease dedicated to advancing and diversifying the pipeline for innovative therapeutics.

No cure or treatment to address the root cause of Alzheimer’s disease currently exists. Research has taken on increased urgency in the wake of recent failures of investigational Alzheimer’s drugs from major pharmaceutical companies to halt or slow brain degeneration.

“At USF Health we have a strategic focus on trying to find the underlying basis and treatments and a cure for Alzheimer’s disease, so it’s very appropriate this year for our speaker to be an expert in Alzheimer’s and related neurodegenerative diseases,” said Stephen Liggett, MD, vice dean for research and professor of internal medicine, molecular pharmacology and physiology, and medical engineering.

“As an MD and PhD, Dr. Levey brings a unique perspective on the translation of laboratory findings into new diagnostic, treatment and preventative approaches for Alzheimer’s disease and its related dementias.”

This year, a record number of poster presentations (over 400) were submitted by trainees from the colleges of Medicine, Nursing, Public Health and Pharmacy on topics ranging from basic and translational science to clinical, epidemiological and outcomes studies.

Nearly all the trainees presenting at Research Day have a faculty mentor who helps guide them through the process of developing a hypothesis, concisely explaining their findings and why they matter, and concluding how their investigation supports or disproves the hypothesis.

“Each year the research is becoming more sophisticated, which is both a reflection of our great faculty, as well as the quality of our students,” Dr. Liggett said. “The energy you feel when you walk into that big hall is contagious… It makes for a great day.”

For the Research Day 2020 agenda, click here.

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Top 10 USF Health News Stories of 2021

Top USF Health Online Stories*

1: USF Health selected as a clinical trial site for Moderna COVID-19 vaccine for children six months to 11 years old.

2: Michael Teng’s Q&A behind the MRNA COVID-19 vaccines.

3: USF Health receives a five-year, $44 million grant to test if computerized brain training can reduce the risk of dementia.

4: USF Health researchers suggest the natural compound in basil may protect against Alzheimer’s.

5: USF Health conducted an NIH study of allergic reactions to various COVID19 vaccines

6: The USF Health Morsani College of Medicine welcomed the most academically competitive and diverse class of medical students.

7: COVID-19 couldn’t put a damper on the excitement of Match Day 2021.

8: A USF Health emergency medicine resident became a Grammy Award-winning opera choir singer.

9: USF was awarded a four-year, $69.9 million NIH grant for type-1 diabetes research.

10: In the wake of a global pandemic, USF Health returned to full operations.

Top 10 Social Media Stories*

1: USF Health selected as a clinical trial site for Moderna COVID-19 vaccine for children six months to 11 years old.

2: USF Health researchers suggest the natural compound in basil may protect against Alzheimer’s.

3: The USF Health Morsani College of Medicine class of 2024 receive their first white coats.

4: USF Health Morsani College of Medicine welcome the most academically competitive and diverse class in history.

5: USF Health physicians treat car enthusiast with ENT cancer.

6: USF Health neurosurgeons repair spine for thrill-seeking patient.

7: Our USF Health physicians make the top doctors list.

8: USF Health patient makes $25,000 gift to USF Health IBD center

9: USF Health emergency medicine resident became a Grammy Award-winning opera choir singer.

10: Taneja College of Pharmacy announces their move to downtown Tampa.

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USF awarded five-year, $44.4 million NIH grant to test whether computerized brain training reduces dementia risk