USF Health Byrd Alzheimer’s Center and Research Institute
Research News
- Gopal Thinakaran, PhD, Byrd research investigator and CEO among those honored for 2023 USF Outstanding Research Achievement. Gopal Thinakaran has contributed significantly to cell and molecular characterization of BIN1, the second most significant Alzheimer's disease risk gene. In 2022, he was awarded two 5-year R01 grants from NIH with total funding of $7,255,070 to investigate how variations in BIN1 elevate someone's risk for Alzheimer's disease. His research investigated BIN1 function using cell-type-specific conditional knock-out and transgenic mouse models of Alzheimer's disease. He published four papers in 2022, including one in Brain (Impact Factor, 15.26) highlighting BIN1 regulation of region-specific tau pathogenesis and neurodegeneration in a novel mouse model and another in Molecular Neurodegeneration (Impact Factor, 18.88) detailing the discovery of BIN1 function in neuroinflammation. His work has been cited 567 times in 2022. He also organized a successful workshop to train USF researchers on how to apply the state-of-the-art nanoString DSP spatial transcriptomics approaches in their research.
- Danielle Gulick, PhD, Byrd research investigator among those honored for 2023 USF Outstanding Research Achievement. In 2022, Danielle Gulick earned her first R01 funding as a PI, as well as an Alzheimer's Association grant, Pharmaceutical funding and Florida High Tech Corridor funding, all to study various aspects of how alcohol addiction can be driven by external factors and how this addiction impairs neurodevelopment in return. A second R01 submitted in 2022 is pending funding with a percentile score of 12 percent. Gulick also published multiple papers from both her lab’s solo work and collaborations across USF. She earned two awards related to her research in medical education, which she maintains along with her robust teaching responsibilities in both the medical and graduate schools. During 2022, Gulick was also featured in podcasts by the Southern Medical Journal for her research.
- Byrd research Investigator Dr. Blair is awarded the 2023 Cathy and Paul Douglas Scholars in Alzheimer’s Discovery Award. The Byrd Institute announces the award of a $150,000 Douglas Scholar grant to Laura Blair, PhD, an Associate Professor here and Co-PI Brian Blagg, PhD at Notre Dame. With the project title of, “An Aha(1) Disrupter for Tauopathies”, Dr. Blair and Dr. Blagg are supporting the efforts in developing a novel therapeutic for the treatment of Alzheimer’s disease. In addition to the monetary grant support, they will receive access to some of the nation’s leading drug development experts as advisors and mentors through the Harrington Discovery Institute Therapeutics Development Center.
- The USF Neuroscience Institute announces the 2023 winners of the Dorothy Benjamin Graduate Fellowship in Alzheimer’s Disease are Karthick Mayilsamy and Abigail Esquivel.
Karthick Mayilsamy - With a bachelor`s degree in biotechnology from India, I moved to the USA in 2016 to pursue an MS in biotechnology at the Morsani College of Medicine, USF. During this period, I got an opportunity to join the lab of Prof. Subhra Mohapatra as a research assistant. My research work involved understanding the chemokine signaling pathways involving the spleen-brain axis in regulating neurodegeneration in a mouse model of traumatic brain injury (TBI). We also successfully developed a combined nano-cell-based therapy that improved pathological and behavioral outcomes by attenuating neuroinflammation in TBI mice. My doctoral research currently investigates the neurological sequelae of SARS-CoV-2 infection. This study mainly focuses on understanding the cellular and molecular mechanisms involved in developing the early onset of tauopathy due to severe SARS-CoV-2 infection in aged mice. I am honored to receive the Dorothy Benjamin Graduate Fellowship which will support my research and help me to gain insights in the Alzheimer's Disease field by attending conferences and workshops.
- The Byrd Institute congratulates Dr. Gulick and Dr. Blair on their promotions and grant awards.
Dr. Danielle Gulick, PhD- A researcher at the Byrd Institute, was recently promoted to Associate Professor with Tenure. Dr. Gulick also received an Alzheimer's Association research grant award to study how maternal and adolescent alcohol exposure increases the risk of neurodegeneration in the aged brain.
Dr. Laura Blair, PhD- A researcher at the Byrd Institute, was recently promoted to Associate Professor with Tenure. Dr. Blair was also awarded a grant from the Alzheimer’s Association International Research Grant Program to develop a novel model to study resilience in neuropsychiatric symptoms in AD.
- Laura Blair PhD, a researcher at the Byrd Institute, announces her R01 renewal was co-funded by NIA and NINDS. This award will support the validation FKBP51 as a target for tauopathies, like Alzheimer’s disease, and explore the molecular landscape by which FKBP51 genetic variants create a vulnerability for neuropsychiatric symptoms. Neuropsychiatric symptoms are often co-morbid with Alzheimer’s disease and other tauopathies correlate with a faster decline in patients. The total direct costs for this award are $3,438,962 over 5 years.
- The 2023 USF Research Day announces the winners of the poster and oral presentations as Emily Sandefur, Niat Gebru, and Aryeh Sudwarts.
Emily Sandefur- I was an undergraduate student at USF and began basic science research as a volunteer at the Byrd Institute in the Summer of 2015 in the laboratory of Drs. Gulick and Gamsby. I was first motivated to pursue Alzheimer's Disease Research because my grandfather had Alzheimer's. I got admitted to the Integrated Biomedical Sciences Ph.D. program at USF in 2020 and joined Dr. Angèle Parent's laboratory at the Byrd in January 2021. I am investigating how the signaling cascades associated with amyloid precursor protein in select brain areas of the brain can impact wake/sleep patterns and memory consolidation. I am looking into how this signaling can reduce the formation of amyloid beta and pathological tau protein, two hallmarks of Alzheimer's disease. Results emanated from this study were recently presented at the Advances in Sleep and Circadian Science conference and the USF Health Research Day. I was honored to receive the "Best Poster in the Field of Neuroscience" at USF. I especially thank my current and past mentors and lab members for their support and guidance throughout the project.
Aryeh Sudwarts- We found that Alzheimer’s disease risk gene BIN1 is important for microglial phenotypic responses to amyloid and tau pathologies. BIN1 seems to regulate the surface localization of receptors, which are crucial for microglia to respond to CNS challenges. This means that BIN1’s function has consequences highly specific to each pathology. Interestingly, BIN1 effected levels of phosphorylated tau specifically in females, showing that cell type-specific sex differences can affect disease.
- Gopal Thinakaran, PhD, CEO of the USF Health Byrd Alzheimer’s Center and Research Institute along with the members of the Thinakaran lab, 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. Their findings have been published in the peer-reviewed journal Brain: A Journal of Neurology
- The USF Neuroscience Institute announces the 2022 winners of the Dorothy Benjamin Graduate Fellowship in Alzheimer’s Disease are Niat Gebru and Joseph McMillan.
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Niat Gebru- "Born and raised in Eritrea, I moved to the states
to pursue my higher-level education. As a doctoral student in Dr. Laura Blair’s
lab, my work focuses on elucidating the relationship between FKBP51 and
neuropsychiatric disorders, like PTSD and Alzheimer's disease (AD).
FKBP51 in concert with Hsp90 regulates tau proteostasis and positively
correlates with pathological tau. The goal is to identify ways to target FKBP51
to mitigate tau burden in AD pathophysiology. I am grateful to Dorothy Benjamin
and the selection committee for the opportunity and incentive to further my
professional development as well as AD research."
Joseph McMillan- "I’m interested in discovering how genetic risk factors for Alzheimer’s disease led to people getting the disease later in life. In Dr. Gopal Thinakaran’s lab, I’m studying how one of these genetic risk factors, BIN1, contributes to development of Alzheimer’s disease, which is currently a mystery. Using a cool technique called TurboID, I hope to discover BIN1’s protein neighborhood in neurons, allowing us to better understand BIN1’s role in Alzheimer’s disease. I am honored to receive the Dorothy Benjamin Graduate Fellowship, which will support this work and hopefully bring us ever closer to an effective treatment for this devastating disease."
- Dr. Moorthi Ponnusamy, a post-doctoral scholar at the Byrd Institute, was awarded a Fellowship from the Alzheimer’s Association International
Research Grant program.
"I was born, raised, and received my doctorate in India (2018). I have been a neurobiologist for 13 years and am passionate about finding novel strategies to treat devastating neurodegenerative disorders like Alzheimer’s. During my doctoral research, I had the opportunity to participate in a collaborative study with the Thinakaran Lab. and was pleased that he generously accepted me to be a part of his team. As a post- doctoral scholar for the past four years, I have been actively investigating the molecular mechanisms behind the GWAS gene BIN1 as a susceptibility risk factor for late-onset Alzheimer’s disease using cell-type-specific conditional knock-out and transgenic mice. One of the crucial findings from my research is that neuronal BIN1 positively regulates hippocampal microglial APOE expression and the severity of tau pathology. Over the next three years, this Alzheimer’s Association Research Fellowship will help me characterize the interplay between BIN1 and APOE (the top two risk genes for late-onset Alzheimer’s disease) tau pathophysiology and elucidate the molecular mechanisms underlying BIN1-dependent APOE modulation of tauopathy. Finally, I am extremely grateful for receiving the AARF award, and I thank my mentor Prof. Gopal Thinakaran, my dear colleagues, the USF members, and Alzheimer’s Association team members."
- Danielle Gulick, PhD was awarded an NIH RO1 grant for $2,163,989 for over 5 years.
“Effects of circadian desynchrony during adolescent alcohol exposure on immediate and long-term risk of alcohol addiction: role of sleep homeostasis and stress signaling”
This proposal will test the independent contributions of disrupted circadian rhythms and sleep in adolescence to long-term alcohol addiction liability, as well as the potential for chronotherapy to reduce alcohol consumption in both adolescents and adults.
- Bradlee Heckmann, PhD was awarded an NIH RO1 grant for $1,868,750 for over 5 years.
“Regulation of LC3-associated endocytosis and neuroinflammation”
Neuroinflammation is a hallmark of neurodegenerative diseases including Alzheimer’s Disease (AD). The mechanisms which regulate inflammatory responses in the brain are poorly defined. This project is directed at understanding the mechanistic contribution of a novel cellular trafficking pathway, LC3-associated endocytosis (LANDO) to regulating neuroinflammation and putative roles in mitigating neurodegeneration. This project will open new therapeutic avenues for treating neuroimmune diseases including AD.
- Gopal Thinakaran, PhD was awarded an NIH RO1 grant for $2,174,618 for years 1-3; and $1,487,799 for years 4 & 5.
“The role of Alzheimer's disease GWAS risk factor BIN1 in tau neuropathology and propagation in vivo”
Alzheimer’s disease (AD) is a devastating age-associated neurodegenerative disorder with no treatment or means that would prevent it, cure it, or even slow its progression. BIN1, which encodes an adaptor protein, is a significant risk factor for late-onset AD. Our investigation will use inducible and cell-type-specific BIN1 conditional knock-out mice to test BIN1’s role in tau pathogenesis and pathology propagation in vivo and develop novel insights into the role of BIN1 as a late-onset AD risk factor. For more information go to the Thinakaran lab.
- Laura Blair, PhD was awarded an Alzheimer's
Association Research Grant (AARG) for $150,000 for 3 years.
“Developing risk and resiliency models of neuropsychiatric symptoms in AD”
Neuropsychiatric symptoms, like depression, are common early in Alzheimer’s disease (AD). AD patients with affective symptoms experience a faster decline in cognition. One of the current limitations in developing therapeutics to address these issues is a lack of preclinical models. Through this funding, we will develop novel mouse models to address this gap, so we can better understand how neuropsychiatric symptoms speed up AD progression and if resilience can be achieved by regulating associated genes. For more information go to the Blair lab.
- Bradlee Heckman, PhD was awarded $400,,00 for two projects for Asha Therapeutics & Florida Hightech Corridor Sponsored Research.
Project 1: $350,000 for 1 year
“Evaluation of a putative therapeutic target to prevent neurodegeneration and development of novel pharmacological inhibitors”
Project 2: $50,000 for1 year
“Preclinical IND-enabling evaluation of safety and efficacy in the regulation of mitochondrial function in neurodegenerative diseases”
The two industry sponsored projects are designed to test the preclinical safety and efficacy of two new therapeutic compounds for treating neurodegenerative diseases including Parkinson’s Disease and Alzheimer’s Disease. In addition, funding supports new discovery projects for novel targets in both neurodegenerative and neuroimmune diseases.
- Bradlee Hickmann, PhD was awarded $64,000 for1 year for Ventus Therapeutics Sponsored
Research.
“Inflammasome modulation in Alzheimer’s Disease”
This project is directed at evaluating the role of the NLRP3 inflammasome in Alzheimer’s Disease pathogenesis. Further studies are directed at investigating the efficacy of a novel NLRP3 inhibitor in the treatment of AD and neuroinflammation.
- Two Byrd Institute
researchers won awards at the 2021 USF Health Research Day.
Niat Gebru, a second-year Ph.D. student at the USF Health Byrd Alzheimer's Institute, won the "Best Neuroscience Poster Award"
I joined USF as a Research Technician in Dr. Laura Blair’s lab in January 2017. I was inspired by the research that was being done in the lab and at the Byrd in general, so I decided to pursue my Master’s in Bioinformatics and Computational Biology in August 2017 while working as a technician. A year later, I realized I wanted to further my education and decided to apply for the Integrated Biomedical Sciences PhD program at USF. They graciously accepted me, and I joined the class of 2019 shortly after I graduated from the MS program. Most of my work in the lab has focused on how Hsp90 co-chaperones modulate tau as we age and may contribute to Alzheimer’s disease pathology. For my Ph.D. work, I am now studying the relationships between FKBP51 (a co-chaperone of Hsp90) and its role in stress-induced PTSD.
Melike Yuksel, a Post-Doctorate Scholar at the Byrd Institute won "The Morsani College of Medicine Outstanding Post-Doctoral Scholar Research Award".
I have been working as a postdoctoral scholar in Dr. Thinakaran's lab since November 2018 (since October 2019 at USF). I work on the characterization of the biological pathways and pathogenic mechanisms regulated by BIN1, the second most common late-onset Alzheimer's disease risk factor. I am happy for the award and thankful to my mentor, Dr. Thinakaran, my co-workers and to USF community.
- Sara Cazzaro Buosi is one of two awarded the 2021 Dorothy Benjamin Graduate Fellowship
From a young age I was intrigued by how the human body operated and the way diseases could affect the functions it routinely performs. After three years of pursuing a Biology degree at the Universidad Simon Bolivar in Caracas, Venezuela, I decided to transfer to the University of South Florida to finish my undergraduate studies, where I obtained my B.S. in Biomedical Sciences during the Fall of 2016. During my time as an undergraduate student, I was determined to acquire experience in the research field specifically in the study of neurodegenerative diseases. I joined the Ph.D. program in Integrated Biomedical Sciences at USF Morsani College of Medicine during the Fall of 2017. In Dr. Kang’s lab, I have been dedicated to the study of the protein Slingshot 1 (SSH1) and how it affects mitochondria through different pathways in the context of Alzheimer’s disease. SSH1 is a protein phosphatase that has been reportedly involved in Cofilin activation, an actin filament severing protein. Our lab has found that SSH1 is able to activate Cofilin, which then migrates to mitochondria causing mitochondrial dysfunction and toxicity. Additionally, we recently published our work showing how SSH1 is also able to affect mitochondria through the blockage of mitochondrial clearance (mitophagy), due to the dephosphorylation/deactivation of the autophagy cargo receptor P62. We hope our further studies can elucidate the interplay between the different functions of SSH1 in Alzheimer’s diseased brains to better understand this disorder and provide better targets for future AD treatments. I appreciate and are truly proud to be awarded the Dorothy Benjamin Graduate Fellowship to support this research.
- Santiago Rodriguez Ospina is one of two awarded the Dorothy Benjamin Graduate Fellowship
Born in Colombia, I was raised in the US since middle school. I have always been fascinated by science. In my undergraduate years, I had the opportunity to participate in research on enzymes, biological catalyst, and their mechanism of action. Currently, I am a PhD student in the lab of Dr. Laura Blair at the USF Heath Neuroscience Institute. My work is focused on using molecular chaperones, which are helper proteins in the cell, to regulate the accumulation of tau, a primary hallmark in Alzheimer’s disease. More specifically, I am studying how heat shock protein 22 (Hsp22) affects tau. Hsp22, like other small Hsps, interacts with misfolding proteins and holds onto them until they can be processed for refolding or degradation. So far, results from my project have showed that high levels of Hsp22 in areas of learning and memory in mice with tau pathology can preserve the cognitive and nerve cell function. I am currently investigating if fragments of the Hsp22 protein can also protect against tau aggregation, and if these fragments or the full-length Hsp22 can alter tau prion-like seeding in cells. I am grateful to be a recipient of the Dorothy Benjamin Fellow, which will further allow me to study Hsp22 and its effects on Alzheimer’s Disease as well as enrich my training experience by supporting my attendance at a national conference.
- University of South Florida Health neuroscientists discover a defect early in autophagy that may help develop SSH1 inhibitors to treat Alzheimer’s and other neurodegenerative diseases
Neuroscientists at the University of South Florida Health (USF Health) Byrd Alzheimer’s Center report for the first time that the protein phosphatase Slingshot-1, or SSH1 for short, disrupts p62’s ability to function as an efficient “garbage collector” and thereby impairs the disposal of both damaged tau and mitochondria leaking toxins. In a preclinical study, the researchers showed that SSH1’s influence in halting p62-mediated protective clearance of tau was separate from SSH1’s role in activating cofilin, an enzyme that plays an essential part in worsening tau pathology. Their findings were published Oct. 12 in Autophagy.
- Byrd Institute welcomes new researcher
Byrd Institute welcomes Dr. Bradlee Heckmann, PhD, Assistant Professor of Molecular Medicine and Byrd investigator. Dr. Heckmann received his PhD from the Mayo Clinic College of Medicine and postdoctoral training from world-renowned researcher Dr. Douglas Green at St. Jude Children’s Hospital. Dr. Heckmann’s research focuses on the molecular and cellular mechanisms, as well as physiological influences that govern neuroimmunity. He recently discovered a non-canonical use of the autophagy machinery in a process called LC3-associated endocytosis. He further identified a role for this pathway in regulating neuroinflammation and in the prevention of amyloid deposition and neurodegeneration in Alzheimer’s disease. His work at USF Health and the Byrd Alzheimer’s Institute will continue to focus on understanding the non-canonical roles of the autophagy machinery and other mechanisms in regulating neuroinflammation. Cumulatively, Dr. Heckmann and his research program aim to further our understanding of how our brains are protected against neurodegeneration, and how to therapeutically target neurodegenerative diseases, infections, cancer, and beyond.
- Next steps will accelerate our Alzheimer’s Disease Research Center
The three main missions of the Byrd Alzheimer’s Center Division of Basic Research are 1.Identifying the root causes of dementia, 2. Devising promising strategies for therapeutic intervention, and 3. Early detection of dementia. This article discusses the research challenges and plans for the Byrd Institute to build a world-class Alzheimer’s disease (AD) research program.
- USF Research Day 2020 includes focus on Alzheimer’s
Keynote speaker, Allan Levey, MD, PhD, professor and chair at Emory University’s Department of Neurology, shared his perspective on “Racing to a Cure for Alzheimer’s Disease” at the USF Research Day 2020. His presentation on pursuing treatment and a cure for Alzheimer’s directly coincides with a focus of USF Health.
- Beta-arrestin2 increases neurotoxic tau driving frontotemporal dementia
Collaborative research conducted by Byrd Institute laboratories (Drs. Woo, Liggett & Kang) focuses on a new approach to prevent the buildup of brain-damaging tau tangles associated with frontotemporal dementia and Alzheimer’s disease.
- Gopal Thinakaran pursues genetic clues to Alzheimer’s disease pathways
Gopal Thinakaran, PhD, professor of molecular medicine and associate dean for neuroscience research at the USF Health Morsani College of Medicine is conducting research that focuses on understanding genetic risk factors that may offer new therapy targets to delay or protect against age-related cognitive decline. Dr. Thinakaran oversees a laboratory at the Byrd Alzheimer’s Institute where he uses cutting-edge cell biology techniques and mouse models to study the molecular and cellular processes underlying Alzheimer’s disease.
- The USF Neuroscience Institute announces the 2019 winners of the Dorothy Benjamin Graduate
Fellowship in Alzheimer’s Disease.
The Dorothy Benjamin Fellowship is made possible by a generous donation from Dorothy Benjamin with an Endowment for Alzheimer’s Research. Each year PhD students who are doing research in Alzheimer’s disease are eligible to apply for a one to two year fellowship that supports their research. This year two candidates were awarded $12,000 per year. The two candidates are Chao Ma and Yan Yan.
- Byrd NSI Investigator Dr. Blair launches a new
VA-funded research program
The Byrd Institute announces the award of a $950,000 Veterans Affairs (VA) grant to Laura Blair, PhD, an Assistant Professor of Molecular Medicine and a Byrd NSI Investigator. While the incidence of physical wounds has dropped in veterans, many soldiers are returning from deployment suffering from psychological wounds that manifest as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). The major goal of this 4-year study is to develop strategies to deplete the stress-associated protein FKBP51 while deepening the understanding of FKBP51 biology, with the long-range goal of enhancing the psychological resiliency of soldiers and veterans. Such efforts are also expected to help the general population suffering from stress-related neurological disorders that impair cognitive brain function.
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Byrd Institute welcomes Dr. Gopal Thinakaran, PhD, an internationally recognized Alzheimer’s disease researcher from the department of Neurobiology at the University of Chicago. Supported by $5.5 million in National Institutes of Health (NIH) grant funding, his research focuses on cutting-edge molecular and cellular processes underlying Alzheimer’s disease and related dementias. At USF Health, Dr. Thinakaran will assume leadership roles as associate dean for neuroscience research, NSI associate director of research, and Bagnor Endowed Chair in Alzheimer’s Research. He will also serve as Professor of Molecular Medicine and Byrd Institute.
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We are excited to welcome Dr. Angele Parent, PhD, from the University of Chicago. She studies how the brain remembers and what goes wrong with memory storage mechanisms in neurodegenerative diseases, focusing on communication between nerve cells (synaptic transmission) and neuronal plasticity. She recently received a 5-year $1.75 million NIH grant to examine how changes in APP metabolism affect memory in sleep-disturbed Alzheimer’s models. Dr. Parent will serve as Associate Professor of Molecular Medicine and Byrd Institute.
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Interview with Dr. Laura Blair
The April 2019 issue of the eNeuro Journal, an official online scientific journal for the Society for Neuroscience, has featured an interview with Dr. Laura Blair, a Byrd investigator. In the interview, Dr. Blair talks about her recent publication in eNeuro describing the cellular and behavioral deficits in a transgenic mouse model in which the FKBP5 gene is overexpressed. Increased FKBP5 has been associated with several psychiatric disorders. The interview goes on to describe her research philosophy and the focus of her laboratory. Full detailed transcript of the interview and paper can be found here.
- The Byrd Institute is pleased to welcome Dr. Lianchun Wang who has recently joined the Byrd Institute as a Professor of Molecular Pharmacology & Physiology.
- Byrd Institute welcomes Dr. Krishna Bhat, who has recently joined the Byrd Institute as a Professor of Molecular Medicine and the Goldsmith Endowed Chair in Alzheimer’s Disease.
- Congratulations to Dr. Jeremy Baker and Dr. Dylan Finneran for successfully defending their dissertations on November 9th, 2018. Dr. Baker, who also received the Chih Foundation Research and Publication award, will begin his postdoctoral training at the University of Washington and VA Puget Sound in early 2019.Dr. Finneran will be joining our former colleague, Dave Morgan, at Michigan State University. The USF Health-NSI wish Drs. Baker and Finneran great success in their future endeavors.