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Research

Accelerating discovery.

The Les Turner ALS Center builds on the extraordinary history of success in ALS research at Northwestern. We believe that the center model even more closely aligns the work in our labs with that of the ALS Clinic, positioning us to accelerate discovery and get closer to a cure.

Clinical Trials

Browse our list of actively recruiting clinical trials to learn more and find out how you may be able to participate.

SEE ALL TRIALS

Publications

Learn more about the work that we do at the Les Turner ALS Center by browsing recent publications from our labs.

OUR LATEST FINDINGS

Our Labs

 Han-Xiang Deng Lab

  The Han-Xiang Deng lab is focused on understanding the mechanism of neurodegenerative diseases such as  Amyotrophic Lateral Sclerosis.

Research Description

CRISPR/Cas9-mediated gene editing provides potentials for ALS therapeutic development. Efficacy and long-term safety of this approach represent major concerns that remain to be adequately addressed in preclinical studies in vivo. Here, we show that CRISPR/Cas9-mediated genome editing in SOD1-ALS transgenic mice is effective. We did not observe apparent adverse effects in a period of over two years. Detailed analysis of the on-targeting and off-targeting events provides important information for optimization of the targeting design for further therapeutic development.

Visit Dr. Deng's faculty profile for more information

 Colin Franz Lab

  A highly technology-oriented regenerative medicine lab employing in vivo and in vitro models of nerve degeneration and regeneration.

Research Description

As a PM&R-physician and scientist with sub-specialty certifications in neuromuscular and electrodiagnostic medicine, the focus of Franz’s clinical and research agendas are highly integrated. He studies as well as takes care of patients with traumatic neurological injuries, neuropathy, diaphragm muscle weakness and amyotrophic lateral sclerosis (ALS). The Franz lab uses a combination of cellular, molecular, bioengineering and electrophysiological techniques and employs small animal (in vivo) and human stem cell-based (in vitro) models of nerve degeneration and regeneration.

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

Publications

See Dr. Franz's publications on PubMed.

 

Contact

Contact Dr. Franz at 312-238-2078.

 Robert Kalb Lab

  Activity-dependent development of circuits in the central nervous system and neurodegenerative diseases

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, see 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

 Evangelos Kiskinis Lab

  Our laboratory investigates the molecular mechanisms that give rise to neurological diseases using human stem cell-derived neuronal subtypes.

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.

Publications

View Dr. Kiskinis' publications at PubMed

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

Contact Information

Evangelos Kiskinis, PhD
Assistant Professor of Neurology

 Pembe Hande Ozdinler Lab

  Understanding the cortical component of motor neuron circuitry degeneration in ALS and other related disorders.

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.

Publications

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

Contact

Hande Ozdinler, PhD at 312-503-2774

 Teepu Siddique Lab

  We are working to discover causes, understand mechanisms of disease and develop cell and animals model in order to develop rational therapies for neurogenetic and neurodegenerative disorders.

Research Description

Our research laboratory is working to determine the causes of and treatments for neurodegenerative disorders and those that affect the muscle, the neuromuscular junction, peripheral nerves and central control of these systems, in particularly those that involve mitochondria and those that involve motor neuron function, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia and ALS (ALS/FTD), primary lateral sclerosis (PLS), the hereditary spastic parapareses (HSP) and related disorders. Recently, we have discovered novel genetic causes of Parkinson Disease. This laboratory has pioneered the gene discovery approach to ALS and related disorders, engineered the first mouse model and have since identified basic molecular mechanisms of pathology in ALS and ALS/dementia on which rational therapy can be now based.

For more information see the faculty profile of Teepu Siddique, MD.

Publications

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

Contact Us

Teepu Siddique, MD at 312-503-4737

 Jane Wu Lab

  Our team have identified genes important for regulating neuronal guidance and cell migration. We discovered the secreted protein Slit as a ligand for Roundabout (Robo) receptor and a major repellent for axons and neurons

Research Description

The Wu Laboratory seeks to understand molecular mechanisms regulating gene expression and their involvement in the pathogenesis of age-related diseases, with our focus on neurodegenerative diseases and cancer metastasis. Our long-term goal is to identify molecular targets for developing effective therapies for these devastating diseases.

We use a multi-disciplinary approach integrating molecular and cellular assays with animal models and pathological samples to dissect fundamental mechanisms underlying the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis - frontotemporal dementia (ALS-FTD) spectrum disorder. Our studies have uncovered cis-regulatory elements and RNA binding proteins (RBPs) regulating tau pre-mRNA splicing, a process affected in FTD-tau. We are examining RNA binding protein network regulating genes critical for the pathogenesis of AD and related dementia. Recent studies have revealed ALS-mutations in several RBP genes including TDP-43 and FUS. We have established cellular and animal models for TDP-43 and FUS proteinopathies. Using these models and patient samples, we are dissecting mechanisms by which genetic mutations in or dys-regulation of these RBP genes cause neural damage.

Our team have identified genes important for regulating neuronal guidance and cell migration. We discovered the secreted protein Slit as a ligand for Roundabout (Robo) receptor and a major repellent for axons and neurons. Our studies have demonstrated conservation of molecular and mechanisms regulating neuronal migration, leukocyte chemotaxis and cancer cell invasion/metastasis. We have uncovered a number of critical players in the Slit-Robo signaling transduction pathway in neuronal guidance and cancer metastasis. We are investigating molecular mechanisms regulating cell migration and cell-cell communication cancer metastasis.

For more information please view the faculty profile of Jane Wu, MD, PhD or visit the Wu Lab website.

Recent Publications

View a full list of publications by Jane Wu at PubMed

Contact Us

Jane Wu, MD, PhD, at 312-503-0684

 

Our center is a proud member of Northeast ALS (NEALS) Consortium.Visit the Consortium Site