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KEEP IN MIND!
A newsletter for friends and supporters of the Massachusetts Alzheimer’s Disease
Research Center and The Memory Study. Visit us at: madrc.org
SPRING / SUMMER 2020 VOL.8 ISSUE 1
A MESSAGE FROM OUR CHIEF
It feels like eons since we’d last produced and train a wonderful set of Harvard students and junior
another issue of our Center’s KEEP IN MIND colleagues each year, and often also get to host students
newsletter, and we’ll like to thank everyone for from throughout our country and indeed, from Asia,
their patience as we pull together the pieces of a Europe, Australiasia, South America and the Middle East
lengthier newsletter this time around. each year. As you peruse this issue, you will be thrilled to
This issue is of great pride to us, as it showcases some learn more about the awards & achievements of some
of the talented students and scientists from all over the of these teammates who join us in our fight against
world who travel to the MGH in order to train in our devastating brain diseases.
labs and learn more about outstanding patient care.
The accompanying image beside this message is taken
from the front page of the October 3, 1996 issue of the
Harvard Gazette and it is certainly an ‘ancient’ image of
our Center’s Associate Director (Dr. Teresa Gomez-Isla)
and I discerning brain-cell images in our lab during that
era. Teresa was one of our first international trainees/
fellows who had travelled to our shores from Spain to
engage in Alzheimer’s disease research for a few years
before returning to Spain. It is indeed gratifying to see
her come full-circle since that time, returning to MGH
after becoming a leading clinician scientist in Europe, Photo Credit: https://news.harvard.edu/gazette/story/1996/10/
aging-brains-lose-less-than-thought/
to take on the challenge of serving as the Associate
Director of our Center! We have had the honor to recruit Continued on the next page
MORE INFORMATION WAYS TO GIVE
If you would like to learn more about our For information about ways to support the clinical
research studies, please call: 617.643.5200 or care, research, teaching and community health
visit us at www.madrc.org activities of the Massachusetts ADRC, please contact
Liang Yap at 617.726.3987 lyap@partners.org
A MESSAGE FROM THE CHIEF contribute to our growing collection of specimens in
Continued from Page 1 our Center’s “biobank” in order to partner with us in this
innovative research!
To mirror and reinforce our efforts in training the next I know that many of us are concerned about developing
generation of first-rate clinician-scientists, we held dementia in early midlife, right when we are still
our inaugural “John H. Growdon, MD symposium” at providing for our families and actively engaged in our
the MGH on November 25, 2019. The symposium is workplaces and our beloved communities. I would
named in honor of Dr. John Growdon – the founder urge everyone to check out page 28 for a study (the
of our Center and of the MGH’s Memory Disorders ‘HATCH’ study – yes, an acronym again!) led by Dr. Jill
Unit (MDU) clinic and the MGH’s Movement Disorders Goldstein to identify the risks of developing Alzheimer’s
Unit clinic. Dr. Growdon had welcomed and trained so disease in early midlife. A close MGH colleague of ours,
many of our mentees since the beginning of memory Dr. Goldstein has led the federally-funded Clinical
and dementia care at the MGH, and we all owe our Neuroscience Laboratory of Sex Differences in the Brain
heartfelt appreciation to all the speakers, panelists and (www.cnl-sd.mgh.harvard.edu) for decades and she
Keynote Speakers --- all trained by Dr. Growdon – who’d is an expert on sex differences in health and diseases
associated with the central nervous system such as
depression and its connection to heart disease.
In past issues, we had sometimes showcased the talents
of research participants and patients (when they permit
us!) and in that tradition, we are honored to feature the
works and life of novelist Shiao-Shen Yu in the centerfold
of the newsletter. I am sure that you will enjoy learning
more about her books!
On the home front, I am certain that many of you have
Photo courtesy of Dr. John Growden already met our wonderful Ambassador of Clinical
Research – Judy Johanson. We had last featured a
presented at the outstanding event. You can find out
piece written by her in the Spring/Summer 2016 of our
more about the symposium (and Dr. Growdon’s own
newsletter and four years later, we again welcome her
reflections!) on pages 40 & 41 of this issue!
perspectives on her life-paths on page 36!
Have you ever wondered about why we collect blood
In closing, I want to thank each of you for being part
samples and cerebrospinal fluid (CSF) from our research
of the family – it is your dedication and effort that
participants? Also, what is an “LP” (lumbar puncture)?
makes it possible to do everything humanly possible
These acronyms may or may not be found in the
to help each other fight these diseases, and we take
canned alphabet soups that we all enjoy now and then,
great strength and comfort in coming together. All my
but these are vital “biospecimens” that are collected to
colleagues join me in saying “thank you”!
hunt for specific “biomarkers” of dementia and related
neurodegenerative disorders. Do learn more about LPs ~ Brad
& CSFs from Dr. Pia Webb’s piece on page 29, and please
2 keep in mind!
KEEP IN MIND!
A newsletters for friends and supporters of the
Massachusetts Alzheimer’s Disease Research
Center and the Memory Study
SPRING/SUMMER 2020
VOL. 8 ISSUE 1
DIRECTOR, MASSACHUSETTS ADRC
Bradley T. Hyman, MD, PhD
Photo courtesy of commons.wikimedia.org/wiki/ CONTRIBUTING WRITERS
Iman Aganj, PhD
Alois Alzheimer (1864 –1915): “It was here in the years 1886/87
that he presented the disease named after him to the public for Rachel E. Bennett, PhD
the first time in 1906 at the local psychiatric university clinic.”
Simon Dujardin, PhD
Maria Calvo Rodriguez, PhD
IN THIS ISSUE Nancy Coppleman, BA
Sudeshna Das, PhD
Scenes and Celebrations Page 4 Jennifer R. Gatchel, MD, PhD
John H. Growdon, MD
Talent Spotlight Page 5 - 30
Jeanette M. Gunther, MS
More about Lumbar Punctures Judith A. Johanson, BA
by Dr. Pia K. Webb Page 29 Doo Yeon Kim, PhD
Development of Clinical Algorithm Masato Maesako, PhD
to Identify Risk for Alzheimer’s Disease Ayush Noori
in Early Midlife Page 31
Derek H. Oakley, MD, PhD
Words from a Novelist - Alberto Serrano Pozo, MD, PhD
Ms. Shiao-Shen Yu Page 33 Ana C. Silva-Amaral, PhD
A New Path Page 36 Pia K. Webb, MD, PhD
Liang Yap, PhD
Celebrations at the Inaugural
John H. Growdon, MD Symposium! Page 40 GUEST WRITER
Jill M. Goldstein, PhD
Shiao-Shen Yu
DESIGN AND PRODUCTION
Teresita O. Olson, MBA
Scenes and Celebrations!
with local communities, particularly those that
have traditionally been underserved. We have
worked very hard to build a welcoming path for
research participants from all walks of life, along
with their care partners. Much of our outreach
involves education: increasing awareness about
memory loss and aging in a conversational way,
establishing rapport and being available to people
wherever they may be. We do a lot of listening –
Wonderful Nancy (seen second from the left) with
community colleagues! the education process definitely goes both ways! I
see outreach as connecting the dots, seeing how
CONGRATULATIONS to Nancy one person can help another and finding creative
Coppelman of our Outreach, Recruitment solutions to very real, often tragic problems. It
& Education (ORE) Core --- on her receiving is an organic process similar to being a crafts
the 2020 Partners in Excellence Award (category: person — weaving random threads into patterns
Fostering Community). and relationships, creating a human design to
“I see this award as a recognition of all my colleagues support the groundbreaking scientific work being
at MADRC, MGH, CNY & BWH - all of us who work done at the Massachusetts Alzheimer’s Disease
in outreach and recruitment. I think the award Research Center. My role is to be a welcoming
acknowledges the importance of connecting presence at the door to this essential research.”
MORE CELEBRATORY NEWS!
by Liang Yap, PhD
Much congratulations to Yakeel Quiroz,
PhD of our ORE Core for receiving
the MGH’s 2019 Ernesto González
Award last Fall. Together with Martha
Muniz – a clinical research coordinator of the
Harvard Aging Brain study who had also receive
the award – both are commended for their
outstanding efforts to the Latino community!
For more information, visit:: https://www.
massgeneral.org/news/hotline/HTL100419/
Dr. Quiroz (L) and Ms. Muniz (R) with Dr. Gonzalez!
Photo courtesy of MGH
community-contributions
TALENT
ANA CLAUDIA SILVA-AMARAL, PHD
I am originally from Brazil,
specifically from the state
of Minas Gerais, the country’s
storehouse of mineral riches (as
indicated by the name). The state
is the largest producer of coffee
in the country (you’re welcome!)
and an important contributor to
farming and agriculture, which has
pain. This was my introduction to study the brain. I joined Dr. Angela
provided the ingredients to great
neuroscience. I was fascinated by Ribeiro’s neuroscience and cognition
food and drinks. My entire family is
the possibility of using nutrients to laboratory at Universidade Federal
in Brazil and yet, I have lived in the
modulate neurotransmitters and de Minas Gerais (UFMG) as a
US over the years on three separate
help improve our patients’ quality research fellow and learned about
occasions. When I was a child, we
of life and I decided I wanted to molecular and behavioral deficits in
lived in San Diego for one year
“
thiamine deficient rats. At this time,
while my mother was studying
I contacted a researcher in Boston
Psychology. Then back in Brazil, I
who used a prenatal malnutrition
took up volleyball and ended up I was fascinated by model that we were establishing at
returning to the US to go to college the possibility of using UFMG. Through this contact I ended
in Idaho on an athletic scholarship. nutrients to modulate up coming to Dr. Douglas Rosene’s
After college I returned to Brazil neurotransmitters and
laboratory at Boston University. In my
and took up my graduate studies help improve our patients’
in Nutrition. During this time, I
joined a multidisciplinary research
group treating cancer patients
“
quality of life and I
decided I wanted to study
the brain.
PhD project I was able to combine
my background in nutrition and my
interest in the brain to investigate
the long-term effects of prenatal
who suffered from debilitating
Continued on next page
newsletter issue: winter spring 2020 5
protein malnutrition in the brain of
adult rats. After having used animal
models to study the brain, I decided
to pursue research that utilized
human brains and that was more courtesy of thebooksareonthetable.com
Map highlighting Dr. Amaral’s hometown of Minas Gerais
clinically relevant. I transitioned to
a postdoctoral research position in
Dr. Teresa Gomez-Isla lab at MGH. ECOR (“Executive Committee on I consider it a privilege to be part of
Teresa’s expertise as a neurologist Research”)/MGH titled: “Selective this research community at MGH and
has helped me design and conduct partial decrease of glycogen to personally handle such invaluable
experiments that translate to human synthase kinase 3 beta (GSK-3β) brains daily. I am looking forward to
disease. In her lab, I have worked diminishes tau phosphorylation, joining MGH faculty as an Instructor
on two main projects: 1) I used a propagation, and formation of tau in Neurology soon, to continue
transgenic mouse model to study aggregates in the mouse brain”. my work on Alzheimer’s disease
the spreading of pathological tau Presenting the results of my work amidst other talented colleagues
in the brain, and 2) my current to the MGH research community at the MassGeneral Institute for
research focuses on deciphering was a truly rewarding experience Neurodegenerative Disease (MIND).
the traits of resilience to Alzheimer’s and receiving the award a gratifying It seems like the third time was the
pathology using post-mortem recognition for the hard work over charm and, after having been in
human brain tissue. Earlier this year the past couple of years. the US for over thirteen years now,
I received a Poster of Distinction I consider Boston my home away
Award for a poster I presented at from home.
6 keep in mind!
TALENT
DEREK H. OAKLEY, MD, PHD
related dementias. I am using this
group of iPS cells to perform the
research in my AACSF fellowship
under the mentorship of Dr. Brad
Hyman, director of the MADRC,
and Dr. Matthew Frosch, director of
the MADRC neuropathology core.
Broadly, the project will seek to
understand how aggregated forms
of the protein “Tau” effect neurons in
Alzheimer’s disease.
In Alzheimer’s disease, brain cells
(neurons) become sick and develop
aggregations of proteins within the
I am a neuropathologist and undergraduate studies. To complete cell bodies. Tau, a protein normally
post-doctoral fellow at the my MD and PhD degrees, I present in neurons, is the major
Massachusetts Alzheimer’s moved to Columbia University in component of these aggregates.
Disease Research Center New York City, largely due to its
“
(ADRC). Recently, I was awarded strengths in neuroscience and the
the Alzheimer’s Association Clinician emerging field of human stem cell
Scientist Fellowship (AACSF) for my biology. Subsequently, I completed
I am using stem cells
project entitled “Tau aggregation anatomic pathology residency and
derived from autopsy-
and toxicity in patient derived iPS neuropathology fellowship at the
confirmed Alzheimer’s
neurons”. This research project Massachusetts General Hospital/ disease patients to create
uses stem cells made from ADRC Harvard Medical School, where I personalized human
brain bank donors to study the
mechanisms of Alzheimer’s disease.
I am originally from Glen Carbon,
solidified my interests in dementia.
At this time, I also began building a
patient-derived cohort of induced
a dish.
“
models of the disease in
Illinois, and attended Washington pluripotent stem cells (iPS cells) for
University in St. Louis for my research in Alzheimer’s disease and
Continued on next page
newsletter issue: winter spring 2020 7
Photo courtesy of flickr.com
The spread of tau aggregates is the neurons afterwards. Preliminary in neurons. Hopefully, this project
thought to drive cognitive decline data suggest that human stem will help improve our understanding
in Alzheimer’s disease. However, the cell-derived neurons may become of one of the major brain-changes
scientific community does not have sick and die once tau aggregation that occurs in Alzheimer’s disease.
a complete understanding of how has occurred - an observation It will also produce an experimental
tau aggregates in neurons lead to that has not been directly seen system that can be used for many
the neuronal dysfunction and death in animal models of Alzheimer’s future studies, including drug
seen in Alzheimer’s disease. disease. During my fellowship, I will discovery.
perform experiments to confirm
I am using stem cells derived from Being a member of the group at the
this observation and use patient-
autopsy-confirmed Alzheimer’s MADRC and beginning this research
specific stem cells to see if neurons
disease patients to create project is a fantastic opportunity.
derived from Alzheimer’s disease
personalized human models of the I am thankful for the support of
patients are more sensitive to tau
disease in a dish. Our approach uses the Alzheimer’s Association and
aggregates than those derived
time-lapse microscopy to watch very grateful to the patients and
from people without this disease.
individual stem cell-derived neurons families that participate in and
We will also attempt to determine
in a dish over a period of up to one support this work.
exactly which of the multiple forms
month, to induce the formation of
of tau seen in aggregates is most
tau aggregates in these cells, and to
responsible for the negative impacts
then determine what happens to
8 keep in mind!
TALENT
JENNIFER R. GATCHEL, MD, PHD
Growing up in the idyllic
central Texas hill country,
I developed a love of Texas
sports and BBQ and all
things sun and summer. I
also experienced firsthand,
in my close-knit Italian family,
the devastating impact of
neurodegenerative disease: I
witnessed my grandmother, an
Italian immigrant and one of my
primary caregivers, struggle with Dr. Marie A. Bernard (L) – Deputy Director of the National Institute on Aging at
the National Institutes of Health – with Dr. Jennifer Gatchel (R)
the movement and behavioral
changes of Parkinson’s Disease. work, which led to the discovery Following my medical school and
Seeking to better understand this of an insulin signaling pathway graduate school training, I went on
disease process, and, ultimately, shared across affected brain regions to complete Psychiatry residency
to be able to do more to help her in neurodegenerative disease, at Massachusetts General Hospital/
and others who were similarly further fueled my drive to develop McLean Hospital, and then the
affected, I went on to pursue MD/ approaches to prevent or slow Harvard Medical School Geriatric
PhD training in the Baylor College of neuronal degeneration. Together, Psychiatry Fellowship Program.
Medicine Medical Scientist Training these early personal and scientific As I cared for older adults with
Program. There, I worked with Dr. experiences were formative debilitating late life depression,
Huda Y. Zoghbi, an extraordinary in motivating me to pursue a anxiety and memory disorders, I
scientific and professional role career as a physician scientist in became increasingly interested
model, and modeled mechanisms geriatric psychiatry, working at in determining mechanisms
of neuronal death and dysfunction the interface of mental health and underlying these behavioral and
in mice and in cells in a dish. This neurodegenerative disease. cognitive symptoms. Drawing
Continued on next page
newsletter issue: winter spring 2020 9
“
from my graduate school work, and there are few effective treatments.
further motivated to investigate The goals of my BrightFocus project
Although my grandmother
these pathways in patients using were to determine the association
ultimately lost her battle
neuroimaging and fluid biomarkers, between mild psychiatric and
with neurodegenerative
I sought the guidance of a diverse disease, her memory, and behavioral symptoms, memory
“dream team” of research mentors the motivation to help decline, and build-up of Aβ, tau, and
at Harvard: Dr. Deborah Blacker,
and Geriatric Psychiatrist and
epidemiologist; Dr. Gad Marshall
a Behavioral Neurologist with
me today.
“
other older adults like
her, continues to drive
brain pathway changes in normal
older adults and those in the pre-
Alzheimer’s and early AD stages.
Results from this project, published
expertise in neuropsychiatric in the Journal of Alzheimer’s Disease
symptoms in Alzheimer’s Disease and JAMA Network Open, showed
(AD); and Drs. Reisa Sperling and changes In AD. In AD, changes occur that in healthy older adults, mild
Keith Johnson, leaders of the not only in a person’s memory and depressive symptoms are associated
landmark Harvard Aging Brain thinking, but also in their mood with tau in two brain regions of
Study, designed to identify the and behavior. Symptoms such as initial deposition in older adults.
earliest signs of memory decline depression, apathy and withdrawal We also found that brain amyloid
in otherwise healthy older adults. are common and distressing to influences the association between
I additionally benefited from the patients and their families, and can depression and memory, such that
mentorship of Drs. Brent. Forester be just as debilitating, if not more worsening depression over time is
and Olivia Okereke (Geriatric so, than changes in memory and closely associated with declining
Psychiatrists) and Dr. Steven Arnold thinking. These psychiatric and memory and thinking in those
(Psychiatrist and Neurologist), all behavioral symptoms may occur with evidence of elevated amyloid.
accomplished scientific mentors with very early in the disease process, in These findings from my BrightFocus
diverse expertise in neuropsychiatric the “pre-Alzheimer’s” disease stage, project have implications for clinical
disorders in older adults. when a person may have the AD trials in AD. Indeed, they suggest
proteins, amyloid beta (Aβ) and that targeting behavioral symptoms
These mentors have provided
tau, in their brains, but before they could be a potential strategy to
critical guidance as I learned clinical
have developed overt signs of the prevent the clinical symptoms
research principles. Working with
disease. There is currently not a clear of AD, a hypothesis that merits
them, I was additionally awarded a
understanding of why and how testing in future work. To follow
BrightFocus Foundation fellowship
these debilitating psychiatric and up on these findings, I am now
in 2016 to support my work
behavioral symptoms occur, and carrying out an NIH/NIA K23 project
investigating mood and behavioral
10 keep in mind!Photo caption: Baylor College of Medicine,
courtesy of www.desfollowupstudy.org
examining associations among impact in the lives of patients (and being entertained) by my two
mood, memory and pathology and their families, whether by Russian blue cats, Cosmo and Mr.
in older adults with more severe promoting healthy brain aging and Whiskers. My love of Texas football
depression. In recognition of these mental health, training the next and BBQ have persisted, but have
efforts, in 2017 I was selected to generation of geriatric psychiatrists, broadened to include Boston
receive the Outstanding Emerging or advocating for legislative action sports teams, and to sampling and
Research Scientist award by the to support patients and families. I cooking a wide range of diverse
BrightFocus Foundation, and in 2019, enjoy giving talks on these topics cuisines with family and friends,
the Hartford-Jeste Award for Future in the community and to fellow including Italian recipes handed
Leaders in Geriatric Psychiatry by the clinicians and scientists across all down through generations of my
American Psychiatric Association. disciplines, and raising awareness, family. To balance this out, I am an
which can translate into an overall enthusiast of personal training and
Although my grandmother
larger support network for patients fitness (running, interval training,
ultimately lost her battle with
and families. pilates, and yoga), fashion and style,
neurodegenerative disease, her
volunteering at my faith community,
memory, and the motivation to While I have come a far distance
the Paulist Center, and maintaining
help other older adults like her, from the idyllic Texas hill country,
steadfast pursuit of the most
continues to drive me today. Indeed, Boston has become a second
beautiful beaches near and far.
my clinical research interests are home to me. When not carrying
sub-served by a more fundamental out research, I enjoy entertaining
desire to have an even larger
newsletter issue: winter spring 2020 11TALENT
ALBERTO SERRANO-POZO, MD, PHD
Hyman’s mentorship, I investigated
the associations between cognitive
decline and brain autopsy findings
in patients with Alzheimer’s
disease and age-matched healthy
individuals. I am extremely grateful
to our research participants for their
generosity with our brain donation
program; without this invaluable
ultimate gift, we would not have
the possibility of advancing the
research on these terrible diseases.
I was born and raised in received my MD in 2001 at the My scientific publications during
Málaga, a mid-sized city in the University of Málaga School of this period (2008-2013) resulted in
Southern Mediterranean coast Medicine and then completed my my PhD at the University of Seville
of Spain. Professionally, it’s been 11 first neurology residency in 2006 at in 2013. Next, to become a board-
fantastic years in the US, but I cannot the University Hospital Virgen del certified neurologist in the US and
help missing Málaga sunny weather Rocío in Seville (Spain). During those caring for dementia patients while
throughout the year, the amazing years, I became very motivated continuing my research program,
food and, above all, my family. I try to specialize on dementias and I pursued a second neurology
to go back home a couple of times decided to do a 2-year research and residency, which I completed at the
every year to spend quality time with behavioral neurology fellowship University of Iowa in 2017. Lastly,
my parents and siblings. at the same institution. I came to I returned to MGH to complete
the US in 2008 attracted by the a second research and clinical
I am a neurologist specialized in
ground-breaking research being dementia fellowship, directed by
memory disorders and a wet lab
conducted by Dr. Brad Hyman at Dr. Teresa Gómez-Isla, and was
researcher on Alzheimer’s disease
our Massachusetts Alzheimer’s recently recruited to the MGH
and related dementias. My career
Disease Research Center. Under Dr. Memory Division Faculty. To be part
path has been rather atypical. I
Continued on page 14
12 keep in mind!TALENT
AYUSH NOORI
There are few forces as
powerful as the will to live
– a stubborn conviction to keep
breathing and to fight for the
right to stand by your grandchild
at his 17th birthday, high school
graduation, and first day of college.
This summer, I was witness to
this formidable fortitude as my
grandmother battled respiratory
failure, a complication of end-stage
Progressive Supranuclear Palsy (PSP).
PSP is a rare and rapidly progressive fortunate to have the opportunity shared cellular pathways which
neurodegenerative tauopathy which to participate in research efforts underlie neurodegeneration. This
has afflicted my grandmother for at the Massachusetts Alzheimer’s project involved comprehensive
the past decade. Though the disease Disease Research Center. Mentored computational analyses of diverse
has rendered her unable to speak, by Dr. Sudeshna Das and Dr. Alberto datasets, with a plan to validate
see, nor swallow, when I played top Serrano-Pozo, I am committed to these results in worm (C. elegans)
hits of the 70s in her ICU room, my helping further enterprising research models of disease. To image the
grandmother gripped my hand initiatives and seek to contribute worms and track their health
and swayed her limbs to the beat to the effort to develop better and lifespan I built the WormBot,
of the music. She was determined treatment options for patients with an open-source robot from the
to dance. neurodegenerative disorders. University of Washington. For this
research, I was happy to receive
It is this unrelenting spirit which, Over the past year and a half, I
1st place in Biology at the New
since 7th grade, has inspired have conducted a meta-analysis of
Hampshire state science fair this
me to pursue research in published human gene expression
spring, and was a Finalist at the
neurodegeneration. I am a rising data across Alzheimer’s disease, Lewy
2019 International Science and
high school senior at Phillips body dementia, and amyotrophic
Exeter Academy, and am deeply lateral sclerosis (ALS) to identify the
Continued on page 15
newsletter issue: winter spring 2020 13Continued from page 12
of this team of smart and dedicated
clinicians and scientists is highly
motivating.
I have just been honored with
the 2019 NACC New Investigator
Award (NACC stands for National
Alzheimer’s Coordinating Center
and represents the consortium of
about thirty Alzheimer’s Disease
“
Photo courtesy of Eurail.com
to the plaques and tangles My number one aspiration in the lab
My number one that accumulate in the brain of is to help find the mechanism that
aspiration in the lab is to Alzheimer’s disease patients, but fuels the progression of cognitive
help find the mechanism
whether this response is protective decline in Alzheimer’s disease, so
that fuels the progression
or deleterious remains unclear and is that we could eventually develop
of cognitive decline in
Alzheimer’s disease, so currently a hot topic in Alzheimer’s neuroprotective therapies to slow
that we could eventually research. In this specific award- down or even arrest this decline.
“
develop neuroprotective
therapies to slow down or
even arrest this decline.
winning project, I have proposed to
investigate further the nature of the
astrocytic and microglial responses
in Alzheimer’s disease by applying
Next, I am planning to test the
hypothesis that these glial cells are
crucial to disease progression using
Alzheimer’s mouse models. I feel
a novel multi-staining technique on privileged to have the opportunity
single human autopsy brain slices of developing my lab research
Centers across the US). In my initial from our brain bank. This method program while caring for patients
neuropathological studies, I had will allow a deeper profiling of these with dementing conditions at MGH
made several intriguing observations cells with many more markers than memory clinic.
supporting a role of glial (non- traditional staining methods (i.e.
nerve) cells in the progression of more than 10 instead of 2 or 3) and a
Alzheimer’s disease, therefore they better understanding of the effects
became my research focus. These of plaques and tangles on these
brain cells –called astrocytes and non-nerve cell types.
microglia- are known to respond
14 keep in mind!Continued from page 13
Engineering Fair (ISEF) in Phoenix, serve in the same role for young experience would find daunting! He
AZ. ISEF is the largest pre-collegiate scientists who may not have access was fourteen. Though only in high
science competition in the world, to the incredible resources I have school, Ayush quickly learned the
and I was galvanized by sharing been offered. I plan to further my skills required to conduct research at
my research with like-minded work by studying computational a post-graduate level. His meticulous
peers engaged in pioneering neuroscience in college. Ultimately, work succeeded in identifying
investigations across the frontiers though my grandmother may not molecular pathways dysregulated in
of all disciplines of science. This live to see my first day of college, Alzheimer’s, Lewy body dementia,
unforgettable experience has the stories and courage of patients and Amyotrophic Lateral Sclerosis.
energized my resolution to continue like her will forever fuel my passion Ayush has consistently impressed
“
to unmask the secrets for research and help ensure that me with his exceptional energy,
our team of scientists will keep creativity, and motivation. He brings
hunting for a cure. This promise of a humanitarian perspective to
...the stories and courage perseverance gives both her and I the work he conducts inside the
of patients like her will hope, and for that, I am grateful. laboratory: he is driven by his passion
forever fuel my passion for and personal investment in the
for research and help Ayush approached me about a
issues that he is addressing through
“
ensure that our team
of scientists will keep
hunting for a cure.
year and half ago when he needed
help with analyzing data. His
objective was to find a common
gene-expression-signature for
his research. I have little doubt that
one day this young man will bring
us closer to treating a disease that
affects millions and for which there
neurodegenerative diseases, an aim
is currently no cure! – Sudeshna Das,
that most of us with much more
of neurodegeneration, and instilled PhD (mentor)
in me optimism that the we, the
next generation of scientists, will
leave an enduring impact on patient
care globally.
I am indebted to Dr. Hyman and the
Massachusetts ADRC for investing in
the research endeavors of students
like myself and am lucky to have
selfless mentors like Dr. Serrano-
Pozo and Dr. Das who have altered
the trajectory of my research
path. In turn, I hope to one day
Photo caption: Philips Exeter Academy library designed by
architect Louis Kahn
newsletter issue: winter spring 2020 15TALENT
IMAN AGANJ, PHD
My graduate research focused
on electron microscopy and
brain MRI, under Prof. Guillermo
Sapiro’s supervision. I have always
been fascinated by how different
branches of science, engineering,
and medicine came together to
build a device that makes an image
of my brain without opening my
skull, and I was determined to be
a part of the research community
that keeps improving it. I joined Prof.
Bruce Fischl’s Lab for Computational
Neuroimaging as a postdoc fellow in
2011, where I am currently a faculty
Dr. Aganj by the Niagara Falls member. Under his guidance, I
managed to receive a pilot grant
My name is Iman Aganj, from Mass. ADRC, which then led
and I am a researcher at the to a 3-year Alzheimer’s Disease
Martinos Center, Mass General Research grant from the BrightFocus
Hospital, Harvard Medical Foundation.
School. I was born and raised in
The main purpose of the BrightFocus
Iran, received my Bachelor’s degree
grant project is the study of brain
in Computer Science in France, and
connectivity in Alzheimer’s disease.
my Master’s and PhD in Electrical
The human brain has complex
Engineering from the University of
structural and functional networks.
Minnesota. Besides my research,
Network-based analysis of brain
I like watching movies, playing the
white-matter connections is helpful
piano, and hiking.
16 keep in mind!“
indirect structural connections that information as possible from their
may not have been considered by medical images, with the ultimate
standard techniques. We recently goal of improving human health.
My research is focused published our methods and results I have sought to apply theoretical
on innovating technology
(led by my postdoc fellow Dr. Aina ideas, such as deriving mathematical
and developing new
Frau-Pascual) in NeuroImage. formulas or designing algorithms,
medical image analysis
techniques, so researchers to health-related practical problems,
I am working towards securing
and clinicians can with the long-term goal of helping
future funding for this project, so I
extract as much useful ease patients’ suffering from diseases.
“
information as possible
from their medical images
can continue working on imaging
Alzheimer’s disease. Generally, my
research is focused on innovating
technology and developing new
http://iman.mgh.harvard.edu
medical image analysis techniques
(and improving the ones that
in revealing the structural changes already exist), so researchers and
in aging and Alzheimer’s disease, clinicians can extract as much useful
and in discovering biomarkers that
are important for diagnosis and
treatment. The goal of the project
is to build on my background in
brain imaging to develop new
computational methods, especially
those that take indirect neural
pathways into account, and derive
more accurate imaging connectomic
biomarkers for Alzheimer’s disease,
which will help us to better
understand how the brain is affected
in this disease. At the core of the
project are new mathematical
models to account for the brain’s
courtesy of listia.com
newsletter issue: winter spring 2020 17TALENT
MARIA CALVO RODRIGUEZ, PHD
Dr. Maria Calvo Rodriguez (R) with her boyfriend,
Juan del Pozo, in San Juan (Puerto Rico).
I am currently a postdoctoral PhD in 2015 at the University of In 2016, I was very fortunate to
research fellow in Dr. Brian Valladolid (Spain), my hometown join the group of Dr. Bacskai, an
Bacskai’s laboratory at the university. The aim of my PhD internationally renowned expert
Massachusetts General project was to identify intracellular in the field of intravital imaging.
Hospital and Harvard Medical calcium alterations in healthy Currently, I use state-of-the-art
School, in Boston. I have been aging and disease, specifically in microscopy techniques that
fascinated by science since I was a neurodegenerative disorders such allow me to observe even the
little kid. My interest in neuroscience as Alzheimer’s disease, using primary smallest subcellular structures
and neurodegenerative disorders cells collected from rat brains. like a mitochondrion in the living
was sparked when I started my pre- After receiving my PhD, I decided to mouse brain. My current research
doctoral training. How connections focus my post-doctoral research on in the Bacskai group focuses on
are made, how neurons establish translating the phenomena mitochondrial dysfunction in
contact with other neurons, and that I studied in cells to a more Alzheimer’s disease, particularly in
how everything is interconnected complex and integrated system, mitochondrial calcium dysregulation
in the brain (neurons, glia, vessels…) the living brain. and associated oxidative stress and
intrigues me. I completed my the neuronal cell death that occurs
18 keep in mind!Postage stamp with image of the University of
Valladolid. Courtesy of colnect.com
in Alzheimer’s disease. Specifically, I Now, I want to continue with my
use in vivo multi-photon microscopy research and extend these novel
to study mitochondrial alterations findings to astrocytes, which to the BrightFocus Foundation
in neurons in mouse models of are a relatively understudied cell for funding this project. My future
Alzheimer’s disease. I was recently type, that potentially play a key aspirations are to establish and
awarded the Junior Faculty Award at role in the pathophysiology of lead a group that develops and
the International Conference Alzheimer’s disease. Malfunction applies translational technologies
on Alzheimer’s and Parkinson’s in the regulation of mitochondrial to better characterize pathological
disease that took place this last dynamics in astrocytes may reduce pathways in neurodegenerative
March in Lisbon, Portugal, for the production of ATP, which may diseases, while performing impactful
the project entitled “In vivo disturb glial-neuronal interactions complementary science focused
mitochondrial calcium dysregulation and cause neuronal death. I recently on subcellular dysfunction in
in neurons in a mouse model of received a BrightFocus Foundation Alzheimer’s disease, ultimately aimed
Alzheimer’s disease”. Fellowship that will fund this project. at finding therapeutic targets to
“
This study aims to find alterations in prevent this debilitating disease.
the correct function and dynamics
Out of the lab, I like practicing sports
of mitochondria in astrocytes
because it helps me relaxing and
With this project I hope I during the development of the
meeting lots of people. Back in
can contribute my grain pathology of Alzheimer’s disease,
Spain, I used to be a spinning and
of sand and advance the with the final goal of identifying
“
research towards finding
a cure for this disease.
new therapeutic targets. With this
project I hope I can contribute
my grain of sand and advance the
aerobics instructor! Now my favorite
activity in Boston is kayaking in the
Charles river when the weather is
good. I also enjoy making crêpes
research towards finding a cure
for breakfast on Sundays, going
for this disease. I am really excited
to Chinatown for dumplings, and
about starting to answer these
travelling to new places.
questions and extremely thankful
newsletter issue: winter spring 2020 19TALENT
MASATO MAESAKO, PHD
Dr. Maesato with his wife Marie and daughters Emiri
(l) and Sara (r). Multi-tasking (i.e. being an academic
scientist and a good husband/dad) is truly challenging!
Induced pluripotent stem (iPS) technical skills in molecular biology. on presenilin (PS)/γ-secretase
cells technology was developed My work investigating the roles biology in the Dr. Berezovska
in 2006 at Kyoto University/ of diet and exercise in Alzheimer’s lab since PS/γ-secretase is not
Japan. In the same year at the disease (AD) mouse models only involved in many essential
same place, I was an undergraduate resulted in a series of publications biological events (e.g., development,
student and thus was lucky that support the beneficial roles neurogenesis, neuronal survival,
enough to find how impressively of exercise. It was an honor to be etc.) but also plays significant roles
this technology impacts scientific selected one of my first author in the broad range of diseases that
community all over the world. This papers as The Journal of Biological are related to brain, skin, immune
experience naturally inspired me to Chemistry Paper of the Year 2012. system, etc. Most clear link is with
become a scientist. Alzheimer’s disease (AD) since
In 2014, I moved to Dr. Berezovska
dominantly inherited missense
During my time as a graduate lab at MGH as a post-doc fellow
mutations in the genes encoding
student, I was trained by Dr. Ayae to learn cutting-edge techniques
PS have been identified in the
Kinoshita (who worked for Dr. in microscopy that include
families of Alzheimer’s disease (FAD),
Brad Hyman’s laboratory at MGH Förster resonance energy transfer
highlighting its importance in
as a post-doc/instructor and now (FRET) imaging and multiphoton
AD pathogenesis.
a professor at Kyoto University) microscopy. I have mainly focused
and I could obtain broad range of
20 keep in mind!Fushimi Inari Shrine, Kyoto.
Photo courtesy of Glenn Taylor/ Flickr
Dr. Berezovska’s strong expertise secretase within the cell. Fortunately, association with diseases (e.g., AD,
has allowed me to recently develop I was able to receive the BrightFocus skin cancer, etc.). It could also enable
and validate a novel FRET-based Foundation Fellowship, which a breakthrough needed for more
biosensor that enables monitoring would support to 1) improve the efficient preclinical drug testing and
PS/γ-secretase activity in real time. sensitivity of biosensor that we for a successful clinical trial design.
PS/γ-secretase activity can be have recently developed to monitor
My future endeavor is to develop
color-coded and mapped over the PS/γ-secretase activity in cells and 2)
new assays that are useful in
entire image of a cell. Therefore, express and validate the optimized
translational studies (i.g. drug
our novel biosensor would permit biosensor in the brain of live mice.
discovery and testing its efficacy
to “visualize” the activity of PS/γ- Our novel biosensor(s) would allow
in vivo) by utilizing my extensive
“
for the first time to study dynamic
experience in molecular biology
behavior of endogenous PS/γ-
and microscopy since I believe this
secretase longitudinally in different
would be crucial for the transition of
My future endeavor is anatomical and subcellular regions
to develop new assays findings from basic research to clinic.
in living mice. Upon completion
that are useful in At last, I am deeply grateful to the
of this work, the proposed studies
translational studies donors of BrightFocus Foundation
will provide a necessary tool
utilizing my extensive for better understanding of the
who made this research possible.
“
experience in molecular
biology and microscopy
dynamics of PS/γ-secretase and its
newsletter issue: winter spring 2020 21TALENT
RACHEL E. BENNETT, PHD
Dr. Bennett receiving an award from Mr. Art
Taylor (CEO of the BBB Wise Giving Alliance)
I grew up in Phoenix, Arizona researchers could make Alzheimer’s but sitting at the microscope one
and have been interested disease changes visible. Being able day we happened to notice that
in the brain since I took a to actually see the disease drove blood vessels in diseased brain
high school field trip to a me to ask questions about the brain looked different than in healthy
brain bank, which stores tissues works and specifically, what causes it brain. This observation set us on
donated to research, similar to the to stop working in Alzheimer’s. a path to exploring new ideas
Massachusetts Alzheimer’s Disease about how the brain (and not just
I joined Brad Hyman’s Alzheimer’s
Research Center at MGH. I remember neurons!) is altered by disease and
disease research lab as a
one of the scientists pulling out a I am increasingly fascinated by the
postdoctoral fellow in 2014 to try to
small microscope and a slide with incredibly interesting biology of
answer some of these questions. I
a tiny piece of cortex on it that brain vasculature.
was drawn to the lab because Brad
had been stained for Alzheimer’s
is at the forefront of developing Blood vessels play an important
disease plaques. On the slide we
microscopy tools to help visualize role in supplying the brain with the
saw neurons and cells packed
changes taking place in the brain. oxygen and nutrients necessary to
together with splotchy, plaque-like
As a recent neuroscience graduate, keep neurons alive, and the blood
protein deposits spread throughout
I initially focused on neurons and vessels in your brain are unlike those
the section. When I looked at it, it
watching what happens to them found in other parts of the body.
felt like an “ah-ha!” moment: using
as Alzheimer’s proteins accumulate, Like neurons, blood vessels can also
a few simple science techniques
22 keep in mind!Identifying these important vascular
changes has led to an innovative
way of thinking about how we
might treat Alzheimer’s —
if we can find treatments that reduce
inflammation and white blood
cell “clogs” in brain vasculature we
might be able to slow or prevent
neuronal loss.
This research was funded by the
The Wave at Vermilion Cliffs, Arizona. BrightFocus Foundation and I
Courtesy of Flickr
was recognized as their 2018
Outstanding Emerging Scientist
and in 2019 as one of three Donors
Cure New Vision Investigators. In
the future, I am excited to continue
this research by testing drugs that
are already FDA-approved to treat
vascular inflammation to see if they
might be effective in Alzheimer’s
models. I am fortunate to be at
MGH and have access to world-
class collaborators in the Radiology
Department who are developing
Dr. Bennett being interviewed by Mr. Richard Liu of MSNBC new MRI and brain imaging
methods that will help us identify
individuals who might benefit from
“
these treatments. It’s thrilling to see
be affected by the same proteins
a small observation turn into a full-
that accumulate in Alzheimer’s,
blown research project that has real
which causes them to become Identifying these
important vascular implications for helping in the clinic
inflamed, changing their shape and
changes has led to an and I’m looking forward to guiding
recruiting white blood cells to their
surface. Similar to clogging a pipe,
these changes restrict blood flow
vessels and could have devastating
“
innovative way of thinking
about how we might treat
Alzheimer’s
this project forward over the next
few years.
consequence to brain health.
newsletter issue: winter spring 2020 23TALENT
SIMON DUJARDIN, PHD
Dr. Dujardin receiving an award!
I was born more than 30 to join an undergrad program of reactions. I think I really found my
years ago in Belgium. After engineering in biotechnologies in way at that moment! I pursued
spending 5 years there, we moved Paris and obtained a master there. with a PhD program in Lille and
to France where I grew up near While I studied mostly genetics of started to study the dysfunction of
the city of Lille! Lille is a quite nice hematology during my undergrad, i a protein called tau in Alzheimer’s
and active city at the intersection wanted to join a program studying disease. After my PhD, I wanted
of Paris, London and Brussels, all cell biology and physiology and to improve again and nothing
linked by a high-speed train!! My therefore I did a second master better for that purpose than joining
father is a nurse and my mother a in cell biology at the university Massachusetts General hospital /
professor of neuropsychology at of Lille where I started to study Harvard Medical School! So I joined
the university of Lille so I guess that neuroscience. Again, what struck the lab of Pr. Bradley Hyman, one
I had a “background” for science me right away is the beauty and of the most prominent scientist
but surprisingly, I really found a perfection of this network of cells worldwide working in Alzheimer’s,
passion for science only in high all interconnected with specific here at MGH and continued to
school when I realized how perfect functions. Reacting in microseconds study tau. I developed a project to
and beautiful Life is! I decided then and all based on biochemical understand how tau dysfunctions
24 keep in mind!progress through the brain and
ultimately invade the whole brain
killing neurons on its passage... more
importantly we are trying to translate
this knowledge in novel potential
diagnosis and therapeutic tools. We
actually had great results confirming
our hypothesis that the progression
of tau dysfunction in the brain is
closely associated with cell death
and disease progression in patients.
We identified a specific species of
tau that was particularly prone to
Dr. Dujardin with Dr. Brad Hyman
induce pathological formation. We
also understood partially how this
pathology spreads in the brain of
patients. Finally, we try to tackle
the formation of tau dysfunction
by the use of antibodies and got
promising results even if the way is
still long before the translation to
clinic. I got awarded a grant from the
Alzheimer’s Association to continue
and extend this work and I also
obtained the junior faculty award
from the Alzheimer’s disease and
Parkinson’s disease international
conference! I have now the ambition
to extend these results and pursue
other studies that we are currently
developing in the lab. Long term, I
wish I could settle a lab and continue
to work in these passionating courtesy of londonupclose.com
subject! But the way is still long!
newsletter issue: winter spring 2020 25Incheon
fairtale village
Incheon Chinatown
Jajangmyeon Museum
Jayu Park
Courtesy of pngtree.com
26 keep in mind!TALENT
by DOO YEON KIM, PHD
disease mechanisms, which seems
to be much more challenging and
interesting (to me) than general
cell biology. I wrote a letter to
Dr. Rudolph E. Tanzi and Dora M.
Kovacs (mADRC faculty member)
in early 2001. Rudy and Dora are
top Alzheimer’s disease experts
and extremely popular among
Korean scientists. I was surprised
(and happy) to get their response in
Dr. Kim (with cap) with members of the ‘3-D culture’ team. Dr. Tanzi is
a couple of days. They became by
standing right behind Dr. Kim
mentors and my journey towards a
cure for Alzheimer’s disease started.
I am a neuroscientist studying interest in science and engineering
pathogenic mechanisms of made me to choose a track In 2014, we developed a three-
Alzheimer’s disease. I was born toward science and engineering. dimensional (3D) human brain cell
in Incheon, South Korea, a mid-sized I had entered the college as the culture model of Alzheimer’s disease
city in the northern area, which is mechanical engineering major (a.k.a. AD-in-a-dish) (Choi et al.
quite close to North Korea. Actually, but later switched to the biology, 2014). In a conventional cell culture
my father was a refugee from North fascinated by complicated biological system, brain cells are growing
Korea. He escaped to the South machineries that make the life exist. in two-dimensional surfaces as a
before the Korean war. As many flattened single layer, which limits
After getting Ph.D. degree in
Korean parents do, my father and the recapitulation of 3D brain cell
cell biology at Korea Advance
mother scarified a lot for the better networks in human brains. Therefore,
Science and Technology (KAIST),
education of their children, my we created a 3D cell culture system
South Korea, I had been looking
brother and me. My father wished where human brain cells are growing
for the best place to study
me to study law, but my strong in 3D gels that are composed of
neuroscience and neurological
newsletter issue: winter spring 2020 27brain matrix proteins. Interestingly,
we found that 3D culture system
was not only increasing brain
cell interactions but also robustly
accelerated toxic amyloid beta
“
We soon realized that
this unique 3D human
Alzheimer’s disease
brain cell culture
disease. Recently, we have been
awarded another NIH/NIA grant
(1R01AG062547-01), together with Dr.
Winston Hide (Beth Israel Deaconess
Medical Center) to identify resilient
accumulation and amyloid beta- system can provide an pathways for Alzheimer’s disease
driven damages when we grew exciting cellular model patients using human brain
human Alzheimer’s disease brain to study Alzheimer’s transcriptomic database and our 3D
cells, which is the central pathogenic
mechanism of Alzheimer’s disease.
We soon realized that this unique
“
disease in a dish. culture models. Our 3D Alzheimer’s
disease brain models play a central
role in these two projects. If the
3D human Alzheimer’s disease brain similar projects were performed
cell culture system can provide an using mouse models, it would
exciting cellular model to study cost much higher price and pose
(Huston Methodist Hospital) to
Alzheimer’s disease in a dish. potential ethical problem due to the
screen ~2400 compounds including
sacrifice of too many mice.
Since then, we started multiple FDA-approved drugs for their
collaborative projects around our efficacy in reducing pathological My goal of our studies, of course,
human 3D Alzheimer’s disease markers of Alzheimer’s disease in is to find a cure for Alzheimer’s
models. We have been awarded our 3D culture model. In this project, disease. I also hope that our studies
grants from Cure Alzheimer’s Fund we are using bioinformatics tools contribute to develop more precise
and NIH/NIA (1R01AG057635-01A1), to accelerate identifying additional and comprehensive human brain
together with Dr. Stephen Wong candidate drugs for Alzheimer’s models that can be used to study
various neurological diseases as
well as Alzheimer’s disease. In line
with this direction, we recently
developed modified 3D Alzheimer’s
brain models that mimics the brain
inflammation (Park et al., 2018)
and the deficits in blood vessels in
Alzheimer’s disease patients (Shin et
al., 2019). Of course, many challenges
lie ahead. But I am optimistic and will
continue my research path aimed at
ending this horrendous disease.
Dr. Kim (with hands waving) with members of Dr. Rudy Tanzi’s Genetics &
Aging Unit’s members
28 keep in mind!TALENT
PIA K. WEBB, MD, PHD
I joined ACTRU, the
Alzheimer’s Clinical &
Translational Research Unit,
as a staff scientist last winter
to work with the MADRC
biobank and biomarker core.
I am originally from Sweden and
completed my medical and graduate
degrees at the Karolinska Institute around the brain and spinal cord. test numbs the skin with a local
in Stockholm before moving to CSF functions as a cushion or “shock anesthetic before inserting a thin
the Cleveland, Ohio, to do a post- absorber” for the brain, but because needle between two of the lumbar
doctoral fellowship. My intention it is in direct contact with the brain vertebrae into the lumbar cistern, a
was to stay in the U.S. for four years, tissue itself, CSF reflects many of long sac containing CSF and some
but I met my husband in Boston and the molecular changes taking place of the nerve roots extending below
am still here 20 years later! locally within the brain in diseases where the spinal cord itself has
like Alzheimer’s disease. These ended. CSF collection is a routine
An important part of my current
proteins and other molecules are not procedure in the clinical work-up
position is to collect biospecimens
detectable in more easily accessible of many brain disorders and LPs are
such as blood and cerebrospinal
fluids, like blood samples. commonly done in patients with
fluid (CSF) that can be used to
dementia to determine CSF levels
investigate biomarkers, which are A small sample of CSF can be
of Alzheimer biomarkers such as
molecules that provide information obtained through a lumbar
amyloid and tau. In research, we also
about a disease or condition, in puncture, also called an LP or a
measure many other brain proteins
these samples. I am especially spinal tap. An LP is a relatively
to detect if there is any inflammation,
excited about working with CSF. We easy procedure that can be done
metabolic abnormalities, or other
all have about a pint of this crystal- without any special preparations.
markers of brain cell injury. We learn
clear fluid that circulates in and The clinician performing the
Continued on next page
newsletter issue: winter spring 2020 29You can also read
