USF Health Byrd Alzheimer’s Center and Research Institute
- 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.
- 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.