Research Labs

Research Description

Topic 1. Mechanisms underlying dopamine neurogenesis
The floor plate, the ventral organizing center in the embryonic neural tube, patterns the neural tube by secreting the potent morphogen Shh. Using genetic fate mapping, we have recently shown that the midbrain floor plate, unlike the hindbrain and spinal cord floor plate, is neurogenic and is the source of midbrain dopamine neurons (Joksimovic, et al, 2009 Nature Neuroscience, Joksimovic et al. 2009 PNAS). We are interested in understanding pathways that are involved in floor plate neurogenesis and production of dopamine neurons. We have shown that Wnt signaling is critical for the establishment of the dopamine progenitor pool and that miRNAs may modulate the dosage and timing of the Wnt pathway (Anderegg et al, PloS Genetics 2013).

Topic 2. Deconstructing Dopaminergic Diversity
The neurotransmitter dopamine, produced mainly by midbrain dopaminergic neurons, influences a spectrum of behaviors including motor, learning, reward, motivation and cognition. In accordance with its diverse functions, dopaminergic dysfunction is implicated in a range of disorders affecting millions of people, including Parkinson’s disease (PD), schizophrenia, addiction and depression. How a small group of neurons underpins a gamut of key behaviors and diseases remains enigmatic. We postulated that there must exist several molecularly distinct dopaminergic neuron populations that, in part, can account for the plethora of dopaminergic functions and disorders. We are currently working to test this hypothesis and define dopamine neuron subtypes.

Topic 3. MicroRNAs in Schwann cell (SC) differentiation
MicroRNAs, by modulating gene expression, have been implicated as regulators of various cellular and physiological processes including differentiation, proliferation and cancer. We have studied the role of microRNAs in Schwann cell (SC) differentiation by conditional removal of the microRNA processing enzyme, Dicer1 (Yun et al, 2010, J Neurosci) . We reveal that mice lacking Dicer1 in SC (Dicer1 cKO) display a severe neurological phenotype resembling congenital hypomyelination. SC lacking Dicer1 are stalled in differentiation at the promyelinating state and fail to myelinate axons. We are beginning to determine the molecular basis of this phenotype. Understanding this will be important not only for congenital hypomyelination, but also for peripheral nerve regeneration and SC cancers.

For more information, please see Dr. Awatramani's faculty profile.

Publications

View Dr. Awatramani's complete list of publications in PubMed.

Contact Us

Rajeshwar Awatramani, PhD at 312-503-0690

Visit Dr. Batra's faculty profile for more information

For more information about the Bonakdarpour Lab, please visit the Bonakdarpour Laboratory website.

Twitter: @bbonakda

Research Description

The Braga Lab is investigating the relationship between neural activity within large-scale brain networks and cognitive functions that are advanced in humans, such as the use of language or thinking about the past or future. These functions are localized to associative regions of the brain that have disproportionately expanded in recent hominin evolution and are separated from information processing hierarchies devoted to any single sensory modality. By mapping brain networks in association areas with precision within individual volunteers using functional MRI, and measuring neural population activity using intracranial techniques, we can characterize brain networks at high spatial and temporal resolution and make insights into their specialization and function. A major focus of the lab is to study the nature of cross-network interactions and the role these play in different cognitive processes.

For lab information and more, visit Dr. Braga's faculty profile or the Braga Lab website.

Contact Us

rbraga@northwestern.edu

Twitter: @RodBraga

Research Description

We are focused on a group of neurodegenerative diseases collectively known as synucleinopathies, characterized by the aggregation of α-synuclein (α-syn). These include Parkinson's Disease, Dementia with Lewy bodies and Multiple Systems Atrophy among others. We use diverse systems that span from yeast to mammalian models to study these diseases. In particular, we are interested in the role Ca²⁺ signaling plays in the toxicity caused by α-syn and to delineate basic mechanisms of Ca²⁺ signaling relevant to neuronal physiology.

For more information, visit Dr. Caraveo Piso's faculty profile or the Caraveo Piso Lab website.

Publications

Please see Dr. Caraveo Piso's publications on PubMed.

Contact Information

Gabriela Caraveo Piso, PhD

Assistant Professor in Neurology

Ward 10-150

312-503-4492

Research Description

The primary goal of our research is to use gene discovery and molecular biology approaches to identify new treatments for epilepsy. We aim to 1) identify the genetic causes of epilepsy, 2) use stem cell models to understand how genetic mutations can cause epilepsy, 3) develop and test new therapeutics for this condition. Our work is based on the promise of precision medicine where knowledge of an individual’s genetic makeup shapes a personalized approach to care and management of epilepsy.

Current Projects:

• Next generation sequencing in patients with epilepsy
• Alternative exon usage during neuronal development
• Identify the regulatory elements that control expression of known epilepsy genes
• Stem cell genetic models for studying the epigenetic basis of epilepsy

For more information, see Dr. Carvill's faculty profile or the Carvill Lab Website.

Publications

See Dr. Carvill's publications on PubMed.

Contact

Contact Gemma Carvill, PhD

Twitter: @CarvillLab

Research Description

Our lab broadly studies cancer stem cell biology, cellular signaling, RNA biology, and therapy responses in human brain tumors, in particular, glioblastoma (GBM). We have a range of different projects currently underway in glioma cell lines, gliomas stem-like cells (GSCs), patient-derived xenograft (PDX) GBM model, human iPSC-derived glioma organoid model, orthotopic glioma xenograft model in mice, and clinical glioma tumor specimens. Our current research focuses on novel mechanisms/cellular signaling of GSC biology, tumorigenesis, progression, and therapy responses of GSCs and GBMs.

Roles of RNA alternative splicing and RNA-binding proteins in glioma

RNA alternative splicing (AS), an evolutionarily conserved co-transcriptional process, is an important and influential determinant of transcriptome and proteome landscapes in normal and disease states such as cancer. AS is regulated by a group of RNA binding proteins (RBPs) that bind to the cis-acting elements in proximity to a splice site thus affecting spliceosome assembly. In cancers, altered expression of or mutations in RBPs result in dysregulated AS that impacts cancer biologic properties. We have established AS/RBP networks that are dysregulated in both adult and pediatric gliomas through bioinformatic analysis of both public and our own datasets of clinical glioma tumors. We are investigating the biological significance of AS/RBPs dysregulation in glioma progression and therapy response by using human iPSC-derived glioma organoid model and GSC brain xenograft models in animals. In addition, we are exploring novel therapeutic approaches of targeting glioma-associated AS/RBP networks to treat GBMs.

Roles of Non-coding RNAs in glioma 

Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), act as transcription repressors or inducers of gene expression or functional modulators in all multicellular organisms.  Dysregulated ncRNAs plays critical roles in cancer initiation, progression and responses to therapy. We study the mechanisms by which deregulated expression of lncRNAs or circRNAs influence GBM malignant phenotypes through interactions with signaling pathways. We study the molecular consequences and explore clinical applications of modulating ncRNAs and related oncogenic signaling pathways in GBM.  We are establishing profiles of ncRNAs in clinical gliomas and patient-derived GSCs, and study mechanisms and biological influences of these ncRNAs in regulating GSC biology and GBM phenotypes. 

Aberrant DNA and RNA structures in therapy-resistant GBM

Standard of care treatment for GBM includes the DNA damaging agent temozolomide (TMZ), which has a known mechanism of action to target and mutate guanine bases. With this knowledge in hand, we sought to determine the effects of guanine (G) mutations in DNA and RNA secondary structure. G’s are important for creating structures like g-quadruplexes in both DNA and RNA which can affect changes in translation or be used as docking sites for DNA repair and RNA binding proteins. Using whole genome sequencing data along with isogenic drug sensitive and resistant lines, we are investigating the role of G mutations in DNA and RNA secondary structure to determine potential therapeutic avenues with the help of a chemical biologist to create novel drugs to target these TMZ-induced aberrant pathways.

Targeting autophagy to treat glioma

Autophagy is an evolutionarily conserved process that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism, thus serving as a protective mechanism against stressors and diverse pathologies including cancer. We study mechanisms by which phosphorylation, acetylation and ubiquitination of autophagy-related proteins regulate GSC and GBM phenotypes and autophagic response, which, in turn contributes to tumor cell survival, growth and resistance to therapy. We investigate whether disruption of these post-translational processes in autophagy-related proteins inhibits autophagy and enhances the efficacy of combination therapies in GBMs. In collaboration with a medicinal chemist, we are characterizing a next generation of novel autophagy inhibitors that specifically target a key autophagy regulator that we recently reported.

Multi-omics and GBM non-responsiveness to immunotherapies

GBM is categorized as a “cold” tumor that does not respond to current immunotherapies using various immune-checkpoint blockers. Although extensive efforts have been made to sensitize GBM to immunotherapies, the mechanistic studies to determine alternative therapies from understanding the underlying signaling and clinical trial results are still disappointing. We are interested in utilizing the information of multi-omics of clinical gliomas, in particular, proteomics profiling in relation to genomic and epigenomic profiling, to identify potential protein targets that could be the major modulators through post-translational modifications in these “cold” GBM tumors. We will also consider the involvement of tumor microenvironment and immune cells in these conditions. These studies are a brand-new direction that are high-risk and high-reward to turn “cold” GBM tumors to immunotherapy responsive tumors.

For more information, please see Dr. Cheng's faculty profile and lab website.

Publications

View Dr. Cheng's complete list of publications in PubMed.

Contact Us

Shi-Yuan Cheng, PhD at 312-503-5314

Visit us on campus in the Lurie Building, Room 6-119, 303 E Superior Street, Chicago, Illinois 60611.

Research Description

For more information, view the faculty profile of Sherry H-Y Chou, MD.

Recent Publications

View Dr. Chou's full list of publications at Pubmed.

Contact

Twitter: @SherryChou399 

Visit Dr. Deng's faculty profile for more information.

Research Description

Myelin is a multilayer lipid membrane structure that ensheaths and insulates axons, allowing for the efficient propagation of action potentials along axons. Myelin abnormalities are part of a wide range of neurological disorders, including Multiple Sclerosis, leukodystrophies and neurodegenerative disorders. Our efforts to understand the molecular control of myelin formation are crucial in order to intervene, and enhance, myelin formation, remyelination, and recovery.

Our research is dedicated to investigating the mechanisms that regulate myelin-forming cell development and function. Myelin is a multilayer lipid membrane structure that ensheaths and insulates axons, allowing for the efficient propagation of action potentials along axons. Myelin is formed by oligodendrocytes in the central nervous system (CNS), and by Schwann cells in the peripheral nervous system (PNS).

In the CNS, our research is focused on the transcriptional control of oligodendrocyte differentiation and CNS myelin formation. The transcriptional network that controls oligodendrocyte differentiation contains only a handful of transcription factors, many of which have been characterized in considerable detail by us and by others. Nevertheless, our understanding of this transcriptional network is still lacking. Our studies aim to fill this void and fully characterize this transcriptional network. Our main transcription factors of interest are zinc finger protein 24 (Zfp24) and Sp7. Our previous research has identified Zfp24 and Sp7 as transcription factors that are essential for CNS myelination. We are now looking at the upstream effectors and downstream targets of Zfp24, and we are characterizing the role of Sp7 in oligodendrocyte lineage cells. In order to study Zfp24 and Sp7, we are developing novel mice models that allow us to either ablate or activate these transcription factors in oligodendrocyte lineage cells. 

In the PNS, our research is focused on understanding the mechanisms involved in PNS injury, recovery, and remyelination. PNS injury is a critical health concern. Understanding the mechanisms that control the response of Schwann cells to PNS injury is necessary to lay the foundation for future therapies. In our first project, we are focused on the role of the WNT signaling pathway in remyelination of the PNS. In our second PNS project, we are characterizing the effect of PNS demyelination on the sensory neurons.

For lab information and more, see Dr. Elbaz's faculty profile.

Publications

2020

Silicon Nanowires for Intracellular Optical Interrogation with Subcellular Resolution. Rotenberg MY, Elbaz B, Nair V, Schaumann EN, Yamamoto N, Sarma N, Matino L, Santoro F, Tian B. Nano Lett. 2020 Feb 12;20(2):1226-1232. PMID: 31904975.

m6A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination. Xu H, Dzhashiashvili Y, Shah A, Kunjamma RB, Weng YL, Elbaz B, Fei Q, Jones JS, Li YI, Zhuang X, Ming GL, He C, Popko B. Neuron. 2020 Jan 22;105(2):293-309. PMID: 31901304.

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life. Feng W, Li Y, Dao P, Aburas J, Islam P, Elbaz B, Kolarzyk A, Brown AE, Kratsios P. Elife. 2020 Jan 3;9. PMID: 31902393.

2019

Molecular Control of Oligodendrocyte Development. Elbaz B, Popko B. Trends Neurosci. 2019 Apr;42(4):263-277. PMID: 30770136.

2018

Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation. Elbaz B, Aaker JD, Isaac S, Kolarzyk A, Brugarolas P, Eden A, Popko B. Cell Rep. 2018 May 22;23(8):2254-2263.  PMID: 29791837.

2016

Activity-Dependent Myelination Shapes Conduction Velocity. Elbaz B. J Neurosci. 2016 Nov 16;36(46):11585-11586. PMID: 27852767

Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice. Aaker JD, Elbaz B, Wu Y, Looney TJ, Zhang L, Lahn BT, Popko B. ASN Neuro. 2016 Oct;8(5). PMID: 27683878.

Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS. Elbaz B, Traka M, Kunjamma RB, Dukala D, Brosius Lutz A, Anton ES, Barres BA, Soliven B, Popko B. Development. 2016 Jul 1;143(13):2356-66 PMID: 27226321.

2013

WDR81 is necessary for purkinje and photoreceptor cell survival. Traka M, Millen KJ, Collins D, Elbaz B, Kidd GJ, Gomez CM, Popko B. J Neurosci. 2013 Apr 17;33(16):6834-44 PMID: 23595742.

Immunosuppressive drugs, immunophilins, and functional expression of NCX isoforms. Rahamimoff H, Elbaz B, Valitsky M, Khatib M, Eskin-Schwartz M, Elmaz D. Adv Exp Med Biol. 2013;961:275-87. PMID: 23224887.

2010

Cyclophilin A is involved in functional expression of the Na(+)-Ca(2+) exchanger NCX1. Elbaz B, Valitsky M, Davidov G, Rahamimoff H. Biochemistry. 2010 Sep 7;49(35):7634-42. PMID: 20681522.

2008

Modulation of Na+-Ca2+ exchanger expression by immunosuppressive drugs is isoform-specific. Elbaz B, Alperovitch A, Gottesman MM, Kimchi-Sarfaty C, Rahamimoff H. Mol Pharmacol. 2008 Apr;73(4):1254-63. PMID: 18182482.

2007

Cyclosporin A-dependent downregulation of the Na+/Ca2+ exchanger expression. Rahamimoff H, Elbaz B, Alperovich A, Kimchi-Sarfaty C, Gottesman MM, Lichtenstein Y, Eskin-Shwartz M, Kasir J. Ann N Y Acad Sci. 2007 Mar;1099:204-14. PMID: 17446460.

2006

High expression in leaves of the zinc hyperaccumulator Arabidopsis halleri of AhMHX, a homolog of an Arabidopsis thaliana vacuolar metal/proton exchanger. Elbaz B, Shoshani-Knaani N, David-Assael O, Mizrachy-Dagri T, Mizrahi K, Saul H, Brook E, Berezin I, Shaul O. Plant Cell Environ. 2006 Jun;29(6):1179-90. PMID: 17080942.

Contact

For general lab inquiries, please contact Braesen Rader: braesen.rader@northwestern.edu

For Dr. Elbaz please email: benayahu.elbaz-eilon@northwestern.edu

Twitter: @BennyElbaz

Our Mailing Addresses

Dr. Elbaz's Office
Benayahu Elbaz-Eilon, PhD
Department of Neurology
Northwestern University Feinberg School of Medicine
7-665 Morton Medical Research Building
310 East Superior Street
Chicago, IL 60611

The Elbaz Lab
Braesen Rader
Department of Neurology
Northwestern University Feinberg School of Medicine
7-450 Searle Building
310 East Superior Street
Chicago, IL 60611

Staff

Research Description

The Gate lab in Northwestern Neurology works at the interface of the immune system and neurodegenerative disease. The lab is focused on employing human genomics approaches to uncover novel biomarkers and therapeutic targets for neurodegeneration. Chief among our strategies is single cell RNA sequencing (scRNAseq) to identify transcriptional changes in human specimens. We also employ spatial transcriptomics, immunohistochemistry and cytometry approaches to validate genomic changes observed by scRNAseq. The Gate lab is focused primarily on neurodegenerative diseases of aging, including, but not limited to: Alzheimer’s disease, Parkinson’s disease and Amyotropic lateral sclerosis.

For lab information and more, see Dr. Gate's faculty profile.

Publications

See Dr. Gate's publications on PubMed.

Contact

Email David Gate, PhD 

Twitter: @DGateLab

Research Description

The Glaser Lab develops new computational tools to better understand how different brain areas and cell types functionally interact, how neural activity flexibly drives movement and behavior, and how neural activity dynamics change across behaviors, internal states, and diseases.

For more information, visit Dr. Glaser's faculty profile or the Glaser Lab website.

Publications

Please see Dr. Glaser's publications on PubMed.

Contact Information

Research Description

Glutamatergic synapses that include the GluA1 subunit have a privileged role in activity-dependent brain development and this is driven, in part, through the assembly of a large multi-protein complex in the post-synaptic density. A critical molecular component of this complex is the scaffolding protein SAP97.  Among the >90 known SAP97 binding partners we have determined that a novel protein called CRIPT plays an essential role in this process.  Humans with mutations in CRIPT have a severe developmental brain disorder. We are using a variety of approaches to understand the mechanisms by which CRIPT controls synapse biology and dendrite growth including: 1) study of a conditional knock-out (cKO) mouse that we built, 2) super-resolution imaging of glutamate receptors/TARPs/MAGUKs using neurons derived from patient iPS cells and 3) electrophysiology of dissociated neurons and hippocampal slices from the cKO mice.  Insight into the molecular logic of SAP97/CRIPT function will have implications for childhood maladies such as intellectual disability and autism/autism-spectrum disorders.

In our studies of adult onset neurodegenerative diseases such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia we find evidence for maladaptive changes in cellular intermediary metabolism and proteostasis.  Ongoing metabolomics interrogations are uncovering why changes in fuel utilization are toxic and discovering new targets for therapeutic intervention.  The relationship between altered metabolism and perturbed protein homeostasis is also an area of intense interest with special focus on a proteasome adaptor protein called RAD23.  Our experimental platforms are: 1) cells from patients with various genetic abnormalities (i.e., mutations in C9orf72, TDP43, etc.) differentiated into neurons, 2) C.elegans, and 3) primary rat/mouse neurons. Targeting proximal events in neurodegenerative diseases will lead to novel therapeutic approaches.

For lab information and more, visit Dr. Kalb's faculty profile or the Kalb Lab website.

Publications

See Dr. Kalb's publications on PubMed.

Contact

Contact Dr. Kalb at 312-503-5358

Research Description

The Kessler Laboratory focuses on the biology of neural stem cells and growth factors and their potential for regenerating the damaged or diseased nervous system. A major interest of the laboratory has been the role of bone morphogenetic protein (BMP) signaling in both neurogenesis and gliogenesis and in regulating cell numbers in the developing nervous system.  Both multipotent neural stem cells and pluripotent embryonic stem cells are studied in the laboratory. Recent efforts have emphasized studies of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hIPSC). The Kessler lab oversees the Northwestern University ESC and IPSC core and multiple collaborators use the facility. In addition to the studies of the basic biology of stem cells, the laboratory seeks to develop techniques for promoting neural repair in animal models of spinal cord injury and stroke. In particular, the lab is examining how stem cells and self-assembling peptide amphiphiles can be used together to accomplish neural repair. The lab is also using hIPSCs to model Alzheimer’s disease and other disorders. 

For more information see the faculty profile of John Kessler, MD.

Publications

View Dr. Kessler's full list of publications in PubMed.

Contact

Visit Dr. Kim's faculty profile to learn more.

Research Description

Consciousness and awareness depend upon an intricate balance of brain network activity. On any given day, this neural balance is disrupted in over 20% of hospitalized older adults, resulting in delirium, an acute and dramatic disorder of attention and awareness. Despite being the most common neuropsychiatric condition in the hospital, delirium remains underrecognized, poorly understood, and does not have any FDA approved therapies.

Our translationally motivated, basic science research explores how neuromodulators such as acetylcholine and systemic factors such as inflammation influence the function of neural networks critical for attention and awareness. We also lead clinical research in patients to predict who will develop delirium and how we can prevent and treat it. Our work leverages wearable technology to measure brain activity noninvasively, coupled with AI analyses to discover new biomarkers that track and predict the course of delirium.

For lab information and more, visit Dr. Kimchi's faculty profile or the Kimchi Lab website.

Publications

Please see Dr. Kimchi's publications on PubMed.

Contact Us

Eyal Y. Kimchi, MD, PhD

Twitter: @ekimchi

Research Description

The broad objective of our laboratory is to understand the nature of the degenerative processes that drive neurological disease in human patients. We are primarily interested in Amyotrophic Lateral Sclerosis (ALS), Epileptic Syndromes as well as the age-associated changes that take place in the Central Nervous System (CNS). We pursue this objective by creating in vitro models of disease. We utilize patient-specific induced pluripotent stem cells and direct reprogramming methods to generate different neuronal subtypes of the human CNS. We then study these cells by a combination of genomic approaches and functional physiological assays. Our hope is that these disease model systems will help us identify points of effective and targeted therapeutic intervention.

For more information view the faculty profile of Evangelos Kiskinis, PhD, or the Evangelos Kiskinis Lab site.

Publications

View Dr. Kiskinis' publications at PubMed.

Contact

Research

The laboratory of Igor Koralnik, MD, studies how viruses affect the nervous system. These include SARS-CoV-2 in patients with COVID-19, HIV in patients with substance use, as well as the entire virome in patients with neurodegenerative diseases. In addition, the Koralnik Lab is involved in global neurology research with international partners.

For more information and publications see the faculty profile of Igor Koralnik, visit the Koralnik Lab or the Program for Global Neurology.

Publications

See Dr. Koralnik's publications on PubMed.

Contact

Email Dr. Igor Koralnik

Twitter: @IgorKoralnik

Research Description

The overarching goal of my laboratory is to study rare diseases such Huntington’s and genetic forms of Parkinson’s disease, as a window to understanding neurodegeneration across the lifespan. More recently, we have focused on rare lysosomal diseases such as Gaucher’s in order to identify specific targets and mechanisms that contribute to neurodegeneration in Parkinson’s and related synucleinopathies. It is expected that such defined targets will facilitate mechanism-based development of targeted therapies for children with neuronopathis Gaucher’s disease as well as adult-onset synucleinopathies such as Parkinson’s disease. To validate and study these targets and novel therapies in human neurons, we have utilized induced pluripotent stem cells (iPS) generated by reprogramming of patient-specific skin fibroblasts. These iPS cells are differentiated into specific neuronal subtypes in order to characterize the contribution of genetic, epigenetic and environmental factors to disease mechanisms and to test novel therapeutic approaches.

For more information see the faculty profile of Dimitri Krainc or visit the Krainc Lab website.

Recent Publications

View Dr. Krainc's full list of publications in PubMed.

Contact information

Dimitri Krainc, MD, PhD
Ward Professor and Chairman
312-503-3936

Learn more about Dr. Knutson's research at Northwestern Scholars.

Twitter: @klknut

The lab’s current primary focus is the management of severe hepatic encephalopathy in patients with fulminant, acute and acute-on-chronic liver failure and noninvasive detection of cerebral edema.

Visit Dr. Liotta's faculty profile to learn more.

Research Description

The characterization of how genetic changes contribute to increasing disease risk or to disease causality is key to understanding the underlying disease etiology. Through the bioinformatics analysis of next generation sequencing data (whole genome or exome), the Lubbe lab aims to identify novel genes or loci that when altered may contribute to the development of Parkinson’s disease and other neurodegenerative diseases. Furthering our knowledge of the processes that cause Parkinson’s disease could potentially pave the way to the development of novel treatments.

For lab information and more, visit the Lubbe Lab website or Dr. Lubbe's faculty profile.

Contact Information

Steven Lubbe, PhD

312-503-5298

Ward 10-132

Visit Dr. Maas' faculty profile to learn more.

Research Description

We are investigating cellular self-renewal mechanisms, amyloid formation in the brain, and the relationship of these processes to neurodegeneration and aging. We primarily use human neurons made from induced pluripotent stem cells as well as in vitro protein aggregation models to delineate the pathogenic mechanisms of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Our group is largely focused on utilizing neurons from rare lysosomal diseases to study how alterations in biomolecule degradation pathways influence the accumulation and conformation of disease-linked proteins such as alpha-synuclein. Another major effort of the lab is to determine how amyloid formation influences cellular self-renewal mechanisms in neurons, such as lysosomal clearance of damaged macromolecules, and the effect on the aging process.

We use the following techniques and model systems:

• Differentiation of induced pluripotent stem cells into midbrain dopamine neurons to model both rare and common neurodegenerative diseases.
• Analytic biochemical techniques, such as HPLC and size exclusion chromatography, to study protein accumulation and misfolding in neurons.
• Analysis of protein and lipid degradation pathways in neurons with a focus on the autophagic-lysosomal clearance system by a variety of biochemical and cell biological techniques
• Primary neuronal cultures and transgenic mice to study the effect of metabolic pathways on protein accumulation and aging.
• Recombinant protein purification of disease-related proteins to study conformational changes in cell-free in vitro systems.

Publications

For lab information and more, visit the Dr. Mazzulli's faculty profile or the Mazzulli Lab website.

Contact Us

Joe Mazzulli, PhD

312-503-3933

Lab Description

Menichella's lab is especially focused on painful diabetic neuropathy (PDN). PDN is a debilitating affliction present in 26% of diabetic patients with substantial impact on their quality of life. Despite this significant prevalence and impact, current therapies for PDN are only partially effective. Moreover, the molecular and electrophysiological mechanisms underlying neuropathic pain in diabetes are not well understood.

Neuropathic pain is caused by sustained excitability in sensory neurons which reduces the pain threshold, so that pain is produced in the absence of appropriate stimuli. Towards designing more effective therapeutics, our goal is to identify the molecular and physiological mechanisms that shape sustained excitability in sensory neurons responsible for the transition to neuropathic pain in peripheral neuropathies. More specifically we are investigating the role of molecules involved in inflammation such as chemokine and the potential role of microRNAs.

We take advantage of an integrated approach combining pain behavioral tests, electrophysiology studies including current clamp recordings, in vitro and in vivo calcium imaging studies, confocal studies with conditional and transgenic mouse genetic and chemo-genetic silencing of sensory neuron subtypes using mutated hM4D receptor (DREADD) receptors.

Publications

For more publication information see PubMed and for more information see the faculty profile of Daniela Maria Menichella, MD/PhD.

Contact

Daniela Maria Menichella, MD, PhD

312-503-3223

Lab Description

As the director of the NIH-funded Cognitive Neurology and Alzheimer’s Disease Center (CNADC), Dr. Mesulam’s research focuses on cognition and aging. The CNADC’s research ranges from evaluating quality-of-life interventions for Alzheimer’s disease, to understanding the underlying molecular mechanisms of neurodegenerative diseases, and everything in between. Many of the research studies at the CNADC are related to primary progressive aphasia (PPA), a rare dementia syndrome characterized by the progressive loss of language abilities with relative sparing of other areas of cognition. As one of the top referral centers for PPA in the world, they maintain a large cohort of patients who are thoroughly studied using a variety of techniques, including MRI, ERP, and neuropsychological testing. All research patients have the opportunity to participate in the Brain Donation Program, which allows researchers to understand the link between clinical presentation and underlying neuropathologic disease.

Publications

For more information please see the faculty profile of M Marsel Mesulam, MD or visit the The Cognitive Neurology and Alzheimer’s Disease Center (CNADC) website.

Contact Us

Phone: 312-908-9339

Twitter: @NUMesulamCenter

The research interests of Dr. Mundt's lab include innovative approaches to treatment with a focus on patient perspectives, mind-body focused interventions for disorders of sleep and arousal, and examining sleep disturbances in the context of other psychological and physical parameters such as cognition, stress, and metabolic syndrome.

For lab information, please visit Dr. Mundt's faculty profile and the Mundt Lab webpage for more information.

Research Description

The section of neurocritical care combines researchers working on complementary areas of neurological emergencies. Ongoing projects include cerebrovascular autoregulation and cognition (Farzaneh Sorond, MD, PhD), patient-centered outcomes research, translational research for acute intracerebral hemorrhage such as acute correction of platelet activity (Andrew Naidech, MD, MSPH), sleep dysfunction and circadian rhythms in acute illness (Matthew Maas, MD), cerebral edema and hepatic encephalopathy (Eric Liotta, MD), and basic neuroscience (Minjee Kim, MD).

Contact Information

Andrew Naidech, MD, MSPH, FANA

Professor of Neurology

Twitter: @AndrewNaidech

Research Description

The long-term goal of my laboratory is to understand the cellular basis of neurodegeneration. We are testing the idea that neurodegeneration results from derangements in relatively few but strategic sub-cellular pathways. By identifying critical components of these pathways one could begin to not only understand the biology of neurodegeneration, but also embark on the design of novel therapeutic agents.

We are currently studying the autosomal dominant disorder Spinocerebellar Ataxia Type 1 (SCA1), a relentless disease that affects cerebellar Purkinje cells and brainstem neurons. This disorder is caused by a polyglutamine expansion in the involved disease protein and is thus similar to a growing number of disorders, including Huntington disease, that share this mutational mechanism. Patients with SCA1 begin to display cerebellar signs characterized by motor incoordination or ataxia in early to mid adulthood. Unfortunately there is no treatment for this disease and patients eventually succumb from the complications of brainstem dysfunction.

Current Projects

1. Testing the transcriptional hypothesis in SCA1 pathogenesis: 

   One of the earliest features of this disease is change in the gene expression signature within neurons affected in this disease. We are elucidating the pattern of gene expression changes in the vulnerable Purkinje cell population and identifying the contribution of these alterations to pathology.

2. Testing the role of the vascular and angiogenic factor VEGF in SCA1 pathogenesis. 

   One of the genes that we have already found to be down-regulated is the neurotrophic and angiogenic factor VEGF. Importantly, we have discovered that genetic or pharmacologic replenishment of VEGF mitigates SCA1 pathogenesis. These results suggest a novel therapeutic strategy for this incurable disease and a possible cross-talk between the degenerating cerebellum and its microvasculature. We are pursuing mechanistic experiments to learn how low VEGF mediates SCA1 pathology. In addition, we are working actively towards testing the potential for VEGF as a therapy in human ataxic disorders.

3. Testing the role of ataxin-1 misfolding and clearance in disease pathogenesis.

   Several studies suggest that ataxin-1 accumulates in neurons because of its inability to be cleared by the protein-misfolding chaperone pathway. We are testing different strategies to promote ataxin-1 clearance.

In addition to spinocerebellar ataxia, we are also studying genetic parkinsonian and dystonic syndromes.

For more information see the faculty profile of Puneet Opal, MD, PhD or visit the Opal Lab website.

Publications

View Dr. Opal's full list of publications at PubMed.

Contact

Email Puneet Opal, MD, PhD 

Phone: 312-503-4699

Twitter: @PuneetOpal

Lab Staff

Research Associates

Jessica Huang

Postdoctoral Fellows

Edamakanti Chandrakanth Reddy (Chandu), PhD
Dilyan Dryanovski, PhD
Yuan-shih (Jennifer) Hu, PhD
Eitan Israeli, PhD

Graduate Students

Natalie Frederick
Kevin Murnan

Technical Staff

Vicky Hwang

Undergraduate Student

Sean Bald
In-Won Chang

Research Description

We are interested in the cellular and molecular mechanisms that are responsible for selective neuronal vulnerability and degeneration in motor neuron diseases. Our laboratory especially focuses on the corticospinal motor neurons (CSMN) which are unique in their ability to collect, integrate, translate and transmit cerebral cortex's input toward spinal cord targets. Their degeneration leads to numerous motor neuron diseases, including amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis.

Investigation of CSMN require their visualization and cellular analysis. We therefore, generated reporter lines in which upper motor neurons are intrinsically labeled with eGFP expression. We also characterized progressive CSMN degeneration in various mouse models of motor neuron diseases and continue to generate reporter lines of disease models, in which the upper motor neurons express eGFP.

The overall goal in our investigation, is to develop effective treatment strategies for ALS and other related motor neuron diseases. We appreciate the complexity of the disease and try to focus the problem from three different angles. In one set of studies, we try to reveal the intrinsic factors that could contribute to CSMN vulnerability by investigating the expression profile of more than 40,000 genes and their splice variations at different stages of the disease. In another set of studies, we try to understand the role of non-neuronal cells on motor neuron vulnerability and degeneration, using a triple transgenic mouse model, in which the cells that initiate innate immunity are genetically labeled with fluorescence in an ALS mouse model. These studies will not only reveal the genes that show alternative splice variations, but also inform us on the canonical pathway and networks that are altered with respect to disease initiation and progression.

Even though the above mentioned studies, which use pure populations of neurons and cells isolated by FACS mediated approaches, will reveal the potential mechanisms that are important for CSMN vulnerability, it is important to develop therapeutic interventions. One of the approach we develop is the AAV-mediated gene delivery directly into the CSMN via retrograde transduction. Currently, we are trying to improve CSMN transduction upon direct cortex injection.

Identification of compounds that support CSMN survival is an important component of pre-clinical testing. We develop both in vitro and in vivo compound screening and verification platforms that inform us on the efficiency of compounds for the improvement of CSMN survival.

In summary, we generate new tools and reagents to study the biology of CSMN and to investigate both the intrinsic and extrinsic factors that contribute to their vulnerability and progressive degeneration. We develop compound screening and verification platforms to test their potency on CSMN and develop AAV-mediated gene delivery approaches. Our research will help understand the cellular basis of CSMN degeneration and will help develop novel therapeutic approaches.

For more information see the faculty profile of Pembe Hande Ozdinler, PhD or the Ozdinler Lab website.

Visit the Les Turner ALS Center

Publications

View Dr. Ozdinler's full list of publications at PubMed.

Contact

Email Hande Ozdinler, PhD 

Phone: 312-503-2774

Twitter: @DrOzdinler

Dr. Pioro's research focuses on characterizing the MRI abnormalities in the brain and spinal cord of PALS as well as identifying the underlying molecular correlates of the imaging changes in CNS tissue and induced pluripotent stem cells derived from these patients.

For lab information and more, visit Dr. Pioro's faculty profile.

The Popko laboratory has a long-standing interest in the myelin sheath. Myelin is the multilayered membrane structure that surrounds most axons of the central and peripheral nervous systems. This extension of the myelinating glial cells’ plasma membrane promotes the very rapid nerve conduction velocities that are required in higher vertebrates, and it provides critical trophic support to the axons. Myelin is produced by Schwann cells in the peripheral nervous system and by oligodendrocytes in the central nervous system.

Our research interests include studies designed to uncover fundamental aspects of myelinating glial cell development, the myelination process, as well as the detailed function of the myelin sheath. We also devote considerable effort to gaining a better understanding of the neurological disorders that disrupt the myelination process during development and the maintenance of the myelin sheath in adults. In addition, we are particularly interested in developing therapeutic approaches to protect the myelinating cells from cytotoxic insult and to enhance the remyelination of demyelinated axons.

For lab information and more, visit Dr. Popko's faculty profile or the Popko Lab website.

Current research areas include understanding the basis and treatment of circadian rhythm sleep disorders, the effects of sleep loss on performance and safety, and the relationship between sleep and risk for metabolic and cardiovascular disease.

Visit Dr. Reid's faculty profile to learn more.

Research Description

We use biochemistry with discovery-based mass spectrometry to identify the protein perturbations which drive synaptopathies and proteinopathies. Groups of perturbed proteins serve as pathway beacons which we subsequently characterizes in hopes of finding new pathogenic mechanisms and potential future therapeutic targets.

For more information view the faculty profile of Jeffrey Savas, PhD or the Savas Lab website.

Publications

Please see Dr. Savas's publications on PubMed.

Contact

Jeffrey Savas, PhD
Assistant Professor in Neurology
312-503-3089

Research Description

The goal of our research is to help people with neurologic disorders, especially those who are severely paralyzed from stroke, spinal cord injury, traumatic brain injury, or ALS. Our research centers around using neural prosthetics, i.e., human machine interfaces, to help restore or replace function of the injured nervous system. We have developed a myoelectric interface for neurorehabilitation training (MINT) to help people with stroke regain function in their arms. The MINT uses electrical muscle signals to control a cursor in customized video games. This enables them to improve coordination between the muscles.

Brain-machine interfaces (BMIs) offer the capability to “decode” brain signals and use them to control computer cursors, prosthetic limbs, or haptic feedback devices. We are investigating the possibility of using BMIs to help rehabilitate brain function by driving plasticity. We study this in humans with traumatic brain injury. In addition, we are investigating the potential to decode a person’s intended speech directly from his or her brain and using this to restore communication to people who have lost it due to severe paralysis. We also use this powerful paradigm to study the underlying relationship between different types of brain signals, for example, the relationship between field potentials (summed from many neurons in the network) and action potentials of individual neurons.

Publications

For more information see the faculty profile of Marc W. Slutzky, MD, PhD or the Slutzky Lab website.

Contact Us

Email Marc W. Slutzky, MD, PhD

Phone: 312-503-4653

Twitter: @SlutzkyLab

Research Description

Our research program is directed at understanding neurovascular function in health and disease. Specifically, we have been studying the association between cerebral blood flow regulation, structural changes in the brain and the clinical outcomes of acute and chronic cerebrovascular injury. In acute neurovascular disorders, we have validated several novel indices of cerebral blood flow regulation which can now be used to predict the development of vasospasm in subarachnoid hemorrhage and hematoma expansion in patients with intraparenchymal hemorrhage. The availability of these early non-invasive biomarkers will have a significant impact on early interventions to improve outcome in patients with subarachnoid and intraparenchymal hemorrhage. Similarly, in chronic neurovascular disorders associated with aging and neurodegeneration, we have been examining the contribution of vascular disease to mobility impairment and cognitive decline. We have shown that our non-invasive biomarkers of vascular function are strongly associated with cerebral small vessel disease as well as motor and cognitive impairment. Our goal is to expand these studies to include other neurological disorders such as stroke, pre-eclampsia, traumatic brain injury and dementia. Having non-invasive, real-time measure of neurovascular function which can predict clinical outcome in the early phases of brain injury will have significant implications on clinical trials and therapeutic targets designed for the treatment and prevention of these various acute and chronic neurovascular injuries.

For more information, view the faculty profile of Farzaneh A Sorond, MD, PhD. Visit her lab website here.

Twitter: @SorondLab

Recent Publications

View Dr. Sorond's full list of publications at PubMed.

Research Description

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. The progressive degeneration of neurons in regions of the brain important for cognition causes the dementia that slowly robs AD patients of their memories, personalities and eventually their lives.

AD pathology is characterized by two microscopic brain lesions:

• Amyloid plaques: Extracellular deposits of the beta-amyloid peptide (Ab), and the longer 42 amino acid form, Ab42, which is strongly associated with autosomal dominant forms of familial AD
• Neurofibrillary tangles

Ab is generated from the amyloid precursor protein (APP) by endoproteolysis from two proteases called the b- and g-secretases. The b-secretase, a novel aspartic protease termed BACE1, was initially cloned and characterized by our group (Vassar, et al., 1999). BACE1 is required for the generation of all forms of Ab, including Ab42, and therefore is a prime drug target for the treatment of AD.

Our ongoing research focuses on the role of Ab and BACE1 in normal biological processes and in disease mechanisms of relevance to AD, including:

• The functions of BACE1 and the homologue, BACE2 and the cell biology of Ab in neurons
• The role of inflammation in AD pathophysiology
• Novel transgenic and knockout mouse models of AD
• Molecular changes that may occur during brain aging leading to neurodegeneration

For lab information and more, visit the Vassar Lab website or see Dr. Vassar's faculty profile.

Publications

See Dr. Vassar's publications on PubMed.

Contact

Email Dr. Robert Vassar

Phone: 312-503-3361

Research Description

Neurodegenerative diseases have been linked to the misregulation of multiple organelles including mitochondria and lysosomes, which are key for cellular and neuronal function. Moreover, organelles are highly dynamic and investigating their regulation in real-time is crucial for advancing our understanding of cell biology, cellular neuroscience, and neurodegenerative disease mechanisms. We recently identified mitochondria-lysosome contact sites as important regulators for mitochondrial and lysosomal network dynamics, which are implicated in multiple neurological diseases including Parkinson's and Charcot-Marie-Tooth disease. 

Our ongoing research seeks to:

• Use super-resolution live cell microscopy to identify new cellular pathways
• Investigate how mitochondria-lysosome contact sites drive cellular & neuronal homeostasis and human disease pathogenesis
• Explore the roles and regulation of inter-organelle membrane contact sites
• Elucidate how organelle dynamics contribute to neurodegeneration in Parkinson’s, Charcot-Marie-Tooth, ALS & Alzheimer’s disease

For more information, visit the Yvette Wong Lab website or Yvette Wong's faculty profile.

Publications

View Dr. Wong's full list of publications in PubMed.

Contact Us

Email Yvette Wong, PhD

Research Description

The Sleep and Circadian Rhythms Research Program has a large research portfolio and a history of successful NIH funding of cutting-edge translational research and clinical trials in the area of sleep and circadian medicine. Research projects include basic studies on mechanisms of sleep and circadian rhythms regulation as well as translational and patient oriented studies on the role of sleep and circadian rhythms on neurocognitive function, cardio-metabolic health, neurodegeneration and other neurological disorders. The program also has extensive history collaborating with institutions throughout the country on large-multi site, multi-year studies and trials.

Currently, faculty are Principal Investigators or collaborators on studies to understand the mechanisms linking sleep quality, circadian alignment with neurocognitive impairment, mood, cardiovascular and metabolic risk in populations at risk for sleep and circadian disorders.

For more information, see the faculty profile of Phyllis Zee, MD, PhD or visit the Center for Sleep & Circadian website.

Publications

For publication information, see PubMed.

Contact

Email Phyllis C. Zee, MD, PhD

Phone: 312-503-4409

Twitter: @PhyllisZee 

Research Description

The respiratory rhythm is inherently linked to olfaction; it is not possible to encounter an odor without first inhaling through the nose. Thus respiration imposes a natural rhythm of stimulus sampling in the olfactory system. In the mammalian olfactory bulb, local field potentials oscillate in phase with breathing, regulating cortical excitability, synchronizing activity within cell assemblies and coordinating network interactions, thus shaping olfactory sensory coding, memory and behavior. Due to timing constraints with neuroimaging techniques such as functional magnetic resonance imaging (fMRI), and anatomical constraints with surface EEG recordings, very little is known about respiratory oscillations in the human olfactory system. We use invasive EEG methods (iEEG) to examine how the respiratory rhythm is represented in the human olfactory system, and how this representation changes during different attentional states, and in the presence of odor. We are also interested in the propagation of respiratory oscillations from olfactory cortex to other nearby limbic areas such as the amygdala and the hippocampus, and how these limbic respiratory-linked oscillations impact cognitive functions. We are currently developing fMRI and surface EEG protocols for studying human respiratory oscillations originating in olfactory brain regions that don’t require iEEG methods.

Another goal of the lab is to understand the neural correlates of olfactory attentional mechanisms. The olfactory system is anatomically unique in that it has no pre-cortical thalamic relay. Rather, the olfactory system has a very small contingent of fibers projecting to the mediodorsal thalamic downstream from primary olfactory cortex. While this small contingent likely plays a role in olfactory attention, the unique anatomical organization of the olfactory thalamic relay suggests that olfactory attentional mechanisms may differ from other modalities. We use psychophysics, fMRI and iEEG methods to examine attentional mechanisms such as selective attention and predictive coding within the olfactory system.

For lab information and more, visit Dr. Zelano's faculty profile or the Zelano Lab website.

Publications

View Christina Zelano's full publication listing on PubMed.

Contact Information

Christina M Zelano, PhD
Assistant Professor in Neurology
312-503-7244