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About Us


who we are   essential resources    meet our staff   global collaboration

 

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.



 

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.   

Meet Our Staff

William L. Klein, PhD
Director

Professor of Neurobiology 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.
 

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

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

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.
 

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

Maíra A. Bicca
Visiting Scholar

Maíra A. Bicca has a pharmacist degree from the Federal University of Santa Catarina – Brazil. She also holds a Masters degree in Pharmacology and is currently enrolled in a PhD program, both at the same institution. She is at the Klein Lab as a Visiting Scholar as a part of her PhD program started in Brazil. During her undergraduate studies, she joined Dr. João Batista Calixto in his lab (LAFEX – Laboratory of Experimental Pharmacology) as a trainee in science for 3 years before she started her Masters. She has started to work with Aβ oligomers and their role in the neuroinflammation and oxidative stress related to the progression of Alzheimer’s disease. Her research interests include ion channels and G-coupled-receptors that could be involved in the triggering and progression of the disease. In addition, she is interested in the molecular mechanisms and cell signaling intricate in the progress of the disease. Maíra is the current holder of the Jose Ribeiro do Valle Award – Young Scientist, granted by the Brazilian Society of Pharmacology, one of the most prestigious awards in Pharmacology. During her scientific career, besides Alzheimer’s disease, she also collaborates in different research projects about Parkinson’s disease, cardiovascular diseases, post-traumatic stress disorder, epilepsy, multiple sclerosis, pain, colitis and cancer.

In her spare time, Maíra likes to run, bike and dance. She also blogs about her experience in the U.S. You can visit her blog here.

email Ms. Bicca

Recent Lab Members

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.
 

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

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 Salp'tri're Hospital (Paris), and receiving a PhD in Neuroscience at UPMC, performing her doctoral studies in the department of neurodegenerative diseases at Sanofi-Aventis (formerly Synth'labo 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 held the position of Research Assistant Professor. 
 

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 led the laboratory's efforts in synapse cell biology and immunocytochemistry using the University's advanced biological imaging facilities.

email Dr. Lacor

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.
 

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

Adriano S. Sebollela, PhD
Research Assistant Professor

Dr. Sebollela holds a BSc in Microbiology and Immunology and a PhD degree in Biological Chemistry, all from the Federal University of Rio de Janeiro, Brazil. During his scientific career he has participated in projects related to protein folding and interactions, and its correlation to biological activity, as well as transcriptomic analysis in the CNS. His main current scientific interests include structure-neurotoxicity relationship of Aβ assemblies and the characterization of candidate therapeutic antibodies for AD.
 

email Dr. Sebollela

Jason Pitt
Recent PhD Graduate

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.

Mr. Pitt's main research interests include crosstalk between ADDL and insulin signaling and therapeutic approaches to Alzheimer's disease. 

email Mr. Pitt

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.
 

Dr. Lambert's seminal paper (Lambert, PNAS, 1998) introduced the concept of Aβ oligomers, or ADDLs, and has been cited more than 2100 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?

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.
 

 
 

The Klein Lab at Northwestern University
2205 Tech Drive
Evanston, Illinois 60208-3520
847-491-5510

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