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About Us
who we are  essential resources meet our staff global collaboration
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Who We
Are |
We are a neuroscience research
team based at Northwestern University. For more than 15
years our research has focused on the cause of
Alzheimer’s disease, and our discoveries are being used
to develop early detection methods and treatments that
will genuinely help AD patients.
Since our first Alzheimer’s study began, we have built
and maintained an outstanding research laboratory of
highly skilled professionals, a testimonial to our
commitment to Alzheimer’s disease research. Team members
have included Guggenheim and Howard Hughes fellows, and
alumni of the lab have gone on to world class
professional careers (eg. head of neurosurgery, NIH lab
chief, director of biotech company, principle of
consulting firm, vice president for research at a major
pharmaceutical company). Extending our efforts, we
collaborate closely with internationally recognized
colleagues from around the world who share our goals.
Our experiments are designed to uncover the cellular and
molecular changes responsible for dementia. Our
discoveries depend on costly, advanced instrumentation
that facilitate state-of-the art research. While the
goals are challenging and the research demanding, the results are immensely rewarding. |
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Essential
Resources |
To achieve successful results over
the long run, a research entity such as ours requires five
equally critical resources:
GREAT PEOPLE | Bright, motivated and
results-oriented
WORK ENVIRONMENT | Quality lab
workspace and equipment
FINANCIAL SUPPORT | Consistent, on-going commitment
RESEARCH VISIBILITY | Constant, targeted exposure
COLLABORATION | Synergies with like-minded
researchers
We've highly optimized these resources in our operations.
Attracting and retaining bright researchers has been and will
continue to be our priority. |
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Meet
Our Staff |
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 William
L. Klein, PhD
Director
Professor of Neurobiology & Physiology, and of Neurology at Northwestern
University, Evanston, Illinois
Klein and his colleagues have pioneered the concept that memory
loss in Alzheimer’s Disease is initiated by soluble amyloid beta
oligomers, small neurotoxins that target particular synapses and
cause their functional and structural degeneration.
Formerly Director of Northwestern’s Interdepartmental
Graduate Program in Neuroscience, Dr. Klein currently is a
member of the university’s Cognitive Neurology and Alzheimer’s
Disease Center and the Nanoscale Science and Engineering Center.
Dr. Klein serves on the editorial board of the Journal of
Biological Chemistry and the scientific advisory board of Acumen
Pharmaceuticals, a biotech he co-founded.
After graduating from MIT in biology, Dr. Klein carried out
predoctoral studies in protein biochemistry at UCLA with Paul
Boyer (Nobel Prize, Chemistry) and postdoctoral studies in
molecular neurobiology at the National Institutes of Health with
Marshall Nirenberg (Nobel Prize, Physiology and Medicine). His
research team at Northwestern has provided new insights into
physiological synaptic signal transduction and cell biology, and
more recently into the pathobiology of synapses in Alzheimer’s
Disease.
In a seminal contribution, Dr. Klein’s team
discovered that amyloid fibrils are not the only neurotoxins
formed by Aβ peptide and likely not the most important ones: Aβ
also generates small, soluble oligomers that are long-lived CNS
neurotoxins capable of destroying the synaptic basis for memory
and ultimately causing nerve cell death. Klein’s team
established that toxic oligomers (also known as ADDLs) are a
major feature of Alzheimer's disease neuropathology through use
of unique toxin-sensitive antibodies now under development for
therapeutics.
Their discovery that ADDLs are highly elevated in CSF of
Alzheimer’s patients offers promise as a diagnostic biomarker.
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Mechanistic studies have revealed ADDLs to be
gain-of-function ligands that attack particular
synapses, provoking neuronal changes that account for
both memory loss and major features of Alzheimer's
disease neuropathology. As described in the Progress
Report on Alzheimer’s Disease published by the US
Department of Health and Human Services, Aβ oligomers
are now widely regarded as the primary cause of
Alzheimer’s nerve cell damage and memory loss.
Investigations into toxic oligomers of Aβ have provided
an archetypal mechanism now considered applicable to
multiple diseases involving other fibrillogenic proteins
(eg. Parkinson’s disease, Type II diabetes, mad cow
disease).
By explaining why Alzheimer’s is a disease of memory and
accounting for major pathological changes of
Alzheimer’affected brain, ADDL toxicity provides a
unifying molecular mechanism for pathogenesis,
underscoring the importance of ADDLs as targets for
clinical diagnostics and disease-modifying therapeutics.
Dr. Klein's research implicating small oligomeric
species of Aβ (ADDLs) in the mechanism of Alzheimer’s
memory loss underlies new approaches to effective early
Alzheimer’s treatments.
email Dr. Klein 
What's an ADDL 
Representative article by Dr. Klein (pdf)
A partial list of keynote addresses & lectures
delivered by Dr. Klein |
 Pascale
N. Lacor, PhD
Research Assistant Professor
Dr. Pascale Lacor received a MS in Biology of Aging at the
University Pierre et Marie Curie (UPMC - Paris VI) of Paris,
conducting her research at the Raymond Escourolle Neuropathology
Brain Bank at La Salpêtrière Hospital (Paris), and receiving a
PhD in Neuroscience at UPMC, performing her doctoral studies in
the department of neurodegenerative diseases at Sanofi-Aventis
(formerly Synthélabo Research Laboratory).
Dr. Lacor was
awarded a postdoctoral fellowship from Sanofi/Elf Aquitaine to
pursue her training in neuropharmacology, protein biochemistry
and molecular biology at the Psychiatric Institute at the
University of Illinois at Chicago with Professors E. Costa (a
National Academy of Sciences member) and A. Guidotti. Her
research focused on the understanding of the etiology of
psychiatric disease, particularly the specific involvement of
the extracellular matrix protein, Reelin, and its modulatory
role in synaptic plasticity-related proteins (such as Arc) and
the neuropil architecture in mutant mice models for
schizophrenia.
In 2001, Dr.Lacor joined Dr.Klein’s group in the Neurobiology
and Physiology department at Northwestern University where she
holds the position of Research Assistant Professor. She is
also an affiliated faculty member of the Cognitive Neurology and
Alzheimer’s Disease Center of the Feinberg Medical School in
Chicago.
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Dr.Lacor currently investigates
the neurological impact of Aβ oligomers (ADDLs)
and their clinical relevance in the etiopathology of
Alzheimer’s Disease, focusing on the synaptic attack by
these oligomers and the subsequent alteration of
post-synaptic memory-related proteins.
In 2002, Dr.Lacor received a Young Investigator
grant from the Illinois Department of Public Health –
Alzheimer’s Disease Research Fund and an RO3 grant the
following year from the National Institute on Aging to
support her research aimed at understanding the
molecular basis for memory loss in Alzheimer’s disease.
Dr. Lacor’s work has shown that human and synthetic
ADDLs bind specifically to synapses (Gong, PNAS, 2003;
Lacor, J Neurosci, 2004), and discovered that ADDLs
trigger Arc upregulation. More recently she has
established that ADDLs pathologically alter synapse
shape, composition, and abundance, providing a molecular
basis for loss of circuitry in Alzheimer’s Disease
(Lacor, J Neurosci, 2007). Dr. Lacor is leading the
laboratory’s efforts in synapse cell biology and
immunocytochemistry using the University’s advanced
biological imaging facilities.
email Dr. Lacor |
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 Mary
P. Lambert, PhD
Senior Research Assistant
Dr. Mary P. Lambert received her B.S. degree in Chemistry from
Birmingham-Southern College in Alabama, where she earned
admission to Phi Beta Kappa. She received her PhD from
Northwestern University in the Biochemistry Division of the
Department of Chemistry, working in the laboratory of Dr.
Francis Neuhaus.
Dr. Lambert’s postdoctoral training was first in the laboratory
of Neuhaus as an instructor in chemistry and then later as a
postdoctoral trainee in the Klein Lab. She received an NIH
postdoctoral fellowship to pursue purification of the muscarinic
acetylcholine receptor.
A full-time Research Associate in the Klein Lab since 1984, Dr.
Lambert’s research interests include protein biochemistry and
purification, antibody production and characterization, growth
factor pathways, developmental biology, cell biology of
Alzheimer’s Disease and Parkinson’s Disease, diagnostics and
therapeutics related to Alzheimer's, structural analysis of
disease toxins, and measurement of toxins in human disease using
nanotechological approaches.
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Dr. Lambert’s seminal paper (Lambert, PNAS,
1998) introduced the concept of Aβ oligomers, or ADDLs,
and has been cited more than
900 times.*
She is co-first author on a paper reporting the
generation of polyclonal (Lambert, J Neurochem, 2001)
and lead author on a paper about monoclonal antibodies
against ADDLs (Lambert, J Neurochem, 2006). Dr. Lambert
is co-author on other breakthrough papers demonstrating
that ADDLs target synapses (Lacor, J Neurosci, 2004) and
cause a loss of insulin receptors on dendrites (Zhao,
FASEB J, 2007).
She
is the laboratory liaison responsible for coordinating
collaborations using the Klein antibodies. Dr. Lambert
is married and the mother of three grown children. Her
outside interests include traveling, hand bells,
gardening, knitting, and reading.
email Dr.
Lambert
* Why is this number significant? |
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 Pauline
T. Velasco
Senior Life Sciences Researcher
Pauline Velasco has been a member of Dr.
Klein’s research team since 2002. Her prior research experience
at Northwestern University includes almost 25 years in the
laboratory of Dr. Laszlo Lorand, a member of the National
Academy of Sciences.
Her earlier research focused on
Ca2+-dependent post-translational modification of
proteins in a variety of systems including blood coagulation,
erythrocytes, eye lens and fertilized sea urchin egg, especially
cross-linking by enzymes of the endo-γ-glutamine:ε-lysine
transferase type. In addition to identification and
isolation of enzymes and their specific intrinsic substrates,
she characterized Factor XIII-related defects of fibrin
stabilization in patients, including congenital deficiencies,
acquired autoantibodies and a dysfibrinogenemia.
As part of the Klein
research team, she has applied her extensive training in
protein biochemistry to the study of the structure and function
of ADDLs, small, soluble oligomers of the amyloid
β1-42 peptide that may play an important role in synaptic degeneration and
nerve cell death in Alzheimer’s disease.
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Her contributions to the
Klein Lab’s research efforts include the development of
biochemical and immunological assays for identification
and isolation of bioactive structures and their
receptors in neuronal cells.
She has helped to characterize the structure
of Aβ
oligomers (Chromy, Biochemistry 2003) and further define
the specific ADDL species involved in synaptic binding
(Lacor, J Neurosci 2004) which leads to pathological
changes in synapse structure (Lacor, J Neurosci, 2007),
tau hyperphosphorylation (DeFelice, Neurobiol Aging,
2007) and neuronal oxidative stress (DeFelice, J Biol
Chem, 2007).
She has also contributed to the development of
ADDL-specific antibodies (Lambert, J Neurochem, 2006),
an important tool in developing clinical diagnostics and
potential therapeutics. Recent efforts have led to major
progress toward her goal of identifying ligand receptors
of ADDLs responsible for initiating memory loss and
neurodegeneration in Alzheimer’s Disease.
email
Ms. Velasco |
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 Kirsten
L. Viola
Research Lab Manager
Kirsten Viola joined Dr. Klein’s group in
1991 after receiving her Bachelor’s degree in Genetics and
Developmental Biology from Northwestern University. Among her
research interests are the development of assays to measure ADDL
levels in biological samples from Alzheimer's disease patients
and mice models. She also assists in the development of assays
to isolate membrane proteins that act as targets for ADDL
binding and their subsequent proteomic analysis. She also has an
interest in the characterization of ADDL (human and synthetic)
binding to both cultured primary cells and cell lines with an
emphasis on binding characteristics and resulting toxic
responses including those seen via an electron microscope.
Lastly, Kirsten uses her microscopy expertise to characterize
newly developed anti-ADDL antibodies. She was the first to show
that ADDLs bind selectively to cells in a punctate manner. She
was also the first to show that anti-ADDL antibodies block ADDL
binding to hippocampal cells and block ADDL-induced toxicity.
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Kirsten is co-first author on the study showing ADDLs could be
used to generate toxicity-neutralizing polyclonal antibodies
(Lambert, J Neurochem, 2001) and contributed
to the development of ADDL-specific monoclonal antibodies
(Lambert, J Neurochem, 2006). She is also a contributing
author on several seminal papers including the 1998 paper that
introduced ADDLs (Lambert PNAS, 1998), the 2003 paper (Gong,
PNAS, 2003) that showed that ADDLs are relevant human AD, and
the papers that show that ADDLs bind to synapses (Gong, PNAS,
2003 and Lacor, J Neurosci, 2004), alter spine morphology
(Lacor, J Neurosci, 2007), and
induce neuronal oxidative stress (DeFelice, J Biol Chem, 2007).
In her spare time, Kirsten enjoys being a mother to her baby boy, sailing, knitting, and giving in to her obsession with
chocolate.
email Ms. Viola |
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Kyle Wilcox, PhD
Post-Doctoral Fellow
Dr. Wilcox earned his PhD in Biochemistry and Biophysics at the University of North Carolina at Chapel Hill, where he studied under Professor Nikolay V. Dokholyan. His work at Carolina centered around characterizing the oligomerization of Cu,Zn superoxide dismutase (SOD1) as it relates to familial amyotrophic lateral sclerosis (FALS). A proud Iowan, he holds a B.S. in Biochemistry from the University of Iowa.
Kyle's scientific interests include protein oligomerization in neurodegenerative disease and the use of nanotechnology to access historically difficult experimental regimes such as mesoscale macromolecular structures and the characteristics of integral membrane proteins. His goal in the Klein laboratory is to identify and characterize synaptic ADDL receptors using lipid/protein "nanodiscs," in collaboration with Steven G. Sligar at the University of Illinois - Urbana-Champagne. |
Kyle spends his time outside the lab worrying that he should be in the lab.
email Dr. Wilcox |
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 Sergio
T. Ferreira, PhD
Visiting Scholar
Professor of Biochemistry, Dept. Head of Medical Biochemistry,
Federal University of Rio de Janeiro
Dr. Ferreira a senior faculty member with the Department of
Medical Biochemistry at the Federal University of Rio de
Janeiro, Brazil. Dr. Ferreira is an internationally recognized
expert in the biochemical and physical properties of proteins,
and has published extensively on the mechanisms of
amyloidogenesis.
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Dr. Ferreira has also
developed a phage display model for identifying peptide
sequences that can attach to the Aβ peptide.
email Dr.
Ferreira |
 Fernanda G. de Felice, PhD
Visiting Scholar
Associate Professor, Institute of Medical
Biochemistry, Federal University of Rio de Janeiro
Dr. De Felice is a biology graduate with subsequent
graduate training in protein biochemistry and biophysics
at the Federal University of Rio de Janeiro. She
obtained post-doctoral training in cellular and
molecular neurobiology at Northwestern University,
working with the William L. Klein team. |
Her previous work in Alzheimer’s Disease dealt with
characterization of novel small molecule compounds that
block the aggregation and neurotoxicity of Aβ;
demonstration of the protective action of GABA receptor
activation against Aβ-induced neurodegeneration;
demonstration of Aβ oligomer-induced
hyperphosphorylation of tau in hippocampal neurons;
demonstration of NMDA receptor-mediated neuronal
oxidative stress induced by soluble Aβ oligomers;
demonstration of a massive decrease in surface
expression of insulin receptors in hippocampal neurons
exposed to Aβ oligomers.
Dr. de Felice’s experience
in amyloid aggregation and biochemical/cell biological
analysis of neuronal pathologies induced by Aβ oligomers
will be essential to the successful analysis of human
ADDL toxicology.
email Dr. de Felice |
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Jason Pitt
3rd Year Pre-Doctoral Candidate
Jason Pitt
received his B.S. in Psychobiology from the University of
Evansville in 2007. During his undergraduate career he
worked in the lab of Harry Orr at the University of Minnesota
and the lab of Yigong Shi at Princeton University. He is
currently a first year graduate student in the Northwestern
University Interdepartmental Neuroscience Program. His
main research interests are the effects of Aβ on cytoskeletal
regulation and gene expression, as well as possible positive
effects of Aβ.
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Jason spends his time
outside the lab playing guitar/bass/drums, writing, and
playing racquetball. While he wishes he could
sing, this does not appear to be the case.
email Mr.
Pitt |
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Global
Collaboration |
| We believe that working with other
outstanding researchers is not only important but vitally essential. Dramatic
breakthroughs in disease treatments come these synergistic
collaborations.
Without collaboration, time is lost, research dollar
expenditures are duplicated and shared insights never emerge.
We have and will continue to collaborate with
more than two dozen facilities in the US, Australia, Belgium,
Brazil, France, Germany, Japan, China and Israel.
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