Researchers at NYU Langone’s Parekh Center for Interdisciplinary Neurology focus on the common mechanisms of seemingly disparate neurological diseases. We seek to gain insights on cross drivers of pathogenesis, especially those involving non-neuronal components and peripheral immune and nervous systems, in addition to the central nervous system.

By partnering strong clinical and basic research teams across NYU Langone, we incubate novel translational discoveries to develop new mechanistic insights and future therapies for our patient community. We also foster the career of young investigators through their active involvement in the interdisciplinary teams carrying out the projects. Below is a list of our current and ongoing projects.

Current Projects

The following new projects will take place in 2026.

Contribution of Platelet CD37 to Ischemic Stroke

Principal investigators: Tessa J. Barrett, PhD; Alice C. Mosberger, ScD; and Sean Kelly, MD, PhD

Every 40 seconds in the United States someone has a stroke, and many survivors live with lasting disability. Most strokes are caused by a clot that blocks blood flow to the brain. Even when doctors reopen the artery, ongoing inflammation in the injured brain can continue to drive damage and limit recovery.

Our research focuses on platelets, which are the blood cells that help form clots. We’ve uncovered a platelet-driven inflammatory program that may worsen brain injury after stroke. We are now testing whether lessening this harmful platelet response can reduce brain damage and improve recovery, while also mapping how platelets communicate with immune and nerve cells during the critical period after stroke. The goal is safer, more-targeted treatments that protect the brain and help more patients regain function.

Tubulin Polyglutamylase Complex as a Key Regulator of Organelle Trafficking in Neuronal Axons

Principal investigators: Brian D. Dynlacht, PhD, and Esteban O. Mazzoni, PhD

Microtubules play an essential role in trafficking cargoes, including organelles, within cells, and microtubule modifications influence their behavior and function. Defects in microtubule-based trafficking result in mispositioning of organelles. In neurons, organelle mispositioning can cause neurodegenerative diseases. Our preliminary results using a human non-neuronal cell line indicate that the removal of two subunits of a microtubule-modifying enzyme leads to aberrant microtubule behaviors that prevent normal organelle distribution. We aim to investigate the functions of these two subunits in neurons and the connections between tubulin modifications, microtubule-dependent trafficking, and neurodegenerative diseases.

MRI Biomarkers of Gliosis, Axon-Sparing Demyelination, and Repair

Principal investigators: Els D. Fieremans, PhD; Dmitry Novikov, PhD; James L. Salzer, MD, PhD; and Jiangyang Zhang, PhD

Injury to brain white matter underlies many neurological and neurodegenerative diseases, including traumatic brain injury, multiple sclerosis, and Alzheimer’s disease. Some forms of damage can heal, while others cause permanent disability—yet noninvasive imaging cannot currently distinguish between the two. We will develop MRI biomarkers that can identify inflammation, demyelination, and axon loss in mice and humans. Using imaging techniques, we will validate these biomarkers and lay the foundation for precise, noninvasive diagnosis and treatment monitoring across neurodegenerative diseases.

Enhancing Stroke Recovery Outcomes Using Vagus Nerve Stimulation

Principal investigators: Robert C. Froemke, PhD; Alice C. Mosberger, ScD; and Heidi Schambra, MD

Strokes are serious neurological conditions that occur when a brain region does not receive blood flow due to a vessel blockage or rupture. This leads to cell death and substantial loss of function, such as motor impairments: most patients do not fully recover even with long-term therapy. Thus, new cost-effective treatments for stroke are required. Enhancing rehabilitative training by pairing it with vagus nerve stimulation (VNS), a mild electrical stimulation of a peripheral nerve, is a promising new therapeutic approach. However, it is unclear how VNS reorganizes brain circuits to optimize recovery in individual patients. Here, we will study upper-limb motor recovery induced by VNS. We will document improvement in outcomes and perform neural recordings to determine which brain areas and neurotransmitters VNS engages to improve recovery after stroke. These findings will inform novel therapeutic strategies and approaches for stroke patients.

Coenzyme Q10 Repletion in Multiple System Atrophy Using Headgroup Precursors

Principal investigators: Un J. Kang, MD; Thong C. Ma, PhD; Horacio Kaufmann, MD; Michael E. Pacold, MD, PhD; and Esteban O. Mazzoni, PhD

Multiple system atrophy (MSA) is a rapidly progressive fatal neurodegenerative movement disorder without effective therapies. Coenzyme Q10 (CoQ10) levels are consistently lower in MSA patients, and since CoQ10 is essential for metabolism, metabolic dysregulation may contribute to MSA pathogenesis. However, CoQ10 taken as supplements cannot reach the brain at sufficient levels. The Pacold Lab recently identified endogenous precursor molecules that increase CoQ10 biosynthesis. In collaboration, we will test whether these restore CoQ10 levels and normalize metabolism in brain cells. These studies will instruct the design of clinical trials of CoQ10 precursors as therapeutics for MSA.

Improving Resiliency of Human Border-Associated Macrophages (BAM) to Limit Alzheimer’s Disease Progression

Principal investigators: Juan J. Lafaille, PhD, and Dimitris G. Placantonakis, MD, PhD

The brain contains immune cells named border-associated macrophages (BAM), which are extraordinarily good waste cleaners. BAM are important to prevent Alzheimer’s disease (AD); however, we observed that their cleaning capacity deteriorates with normal aging and even faster with AD. We propose determining what causes AD-related deterioration of the macrophages’ cleaning function, with the goal of having more resilient BAM capable of preventing or significantly delaying the onset of AD symptoms. We will use Parekh Center resources to study BAM properties in fresh human brain tissue obtained from surgical procedures.

Epichaperome as Protein Condensate in Neurodegenerative Disease

Principal investigators: Thomas A. Neubert, PhD; Einar M. Sigurdsson, PhD; and Liam J. Holt, PhD

Alzheimer’s and related neurodegenerative diseases can be thought of as a protein connectivity-based dysfunction resulting from a variety of environmental or genetic stresses. In this project, we propose to gain information about how harmful protein connection networks are formed in neurodegenerative disorders, such as Alzheimer’s disease, and to better characterize the biophysical properties of these networks. These experiments will provide knowledge that will help design more specific drugs to interrupt pathogenic molecular networks (epichaperomes) for treatment of Alzheimer’s disease, Parkinson’s disease, and related conditions.

Establishing the Role a Dual Myeloid–Oligodendrocyte Checkpoint Receptor for Multiple Sclerosis and Myelination Disorders

Principal investigators: Jun Wang, PhD, and James L. Salzer, MD, PhD

Multiple sclerosis (MS) is a leading cause of neurologic disability in young adults. MS results from an immune system attack on myelin, the protective coating that surrounds nerves in the brain and spinal cord. Current treatments have limited effectiveness, especially in primary progressive MS. Our research focuses on a novel surface protein. By targeting this molecule, we aim to develop new therapies that both limit inflammatory damage and promote healing in MS and related myelination disorders.

Continuing Projects

The following projects are ongoing.

Wearable Closed-Loop Drug Administration Devices for Neuropsychiatric Diseases

Principal investigators: Haogang Cai, PhD, and Simon Khuvis, MD, PhD

Managing medications for neuropsychiatric illnesses like bipolar disorder (BD) and Parkinson’s disease (PD) is challenging because these medications have narrow therapeutic windows. The effective dose is very close to the dose that can cause side effects. For instance, lithium can prevent suicide in BD, but high doses cause permanent kidney damage and other side effects. Levodopa for PD treats tremors but causes other movement disorders, called dyskinesias. Taking these orally causes large fluctuations in blood levels, which means that, for many patients, they cannot be used without side effects. We propose a novel solution: a patch sensor combined with a medication administration pump. The sensor can be painlessly applied to the skin and would continuously monitor blood levels and adjust dosage in real time through the pump, keeping medication levels within the therapeutic window and reducing side effects and improving treatment outcomes. Although our initial focus is on BD and PD, this platform technology could be adapted for a broad range of diseases and treatments.

Neurodegenerative and Neuroinflammatory Plasma Biomarkers Associated with Epilepsy in Alzheimer’s Disease

Principal investigators: Orrin Devinsky, MD; Jaqueline A. French, MD; and Thomas M. Wisniewski, MD

AD and epilepsy are reciprocally related; AD increases risk for late-onset seizures that occur in 10 to 22 percent of patients, and epilepsy increases risk for cognitive impairment in up to 80 percent of patients. Epileptiform activity and cognitive deficits are linked with tau pathology, with total tau and phosphorylated tau (pTau) increased in AD and epilepsy hippocampi. Specific pTau sites are linked to early AD stages, with increased pTau217 and pTau231 in brain and plasma. However, plasma tau has only been studied in AD and some epilepsy groups.

Tau has not been studied in plasma or neuron-derived exosomes that may better correspond to findings in the brain from AD cases with and without epilepsy. We seek to better understand how epilepsy contributes to the etiology of AD by identifying biomarkers in AD with and without epilepsy, which will inform follow-up mechanistic, diagnostic, and prognostic studies.

Deciphering the Neurobiological Mechanisms of Visual Hallucinations

Principal investigator: Biyu J. He, PhD

Visual hallucination is a mysterious condition that affects patients with a variety of clinical conditions, including age-related vision loss, neurodegenerative disorders, and psychiatric illnesses. Visual hallucinations constitute an important safety risk, are distressing to patients and families, and predict worse clinical outcomes. We hypothesize that several neural factors contribute to visual hallucinations, including hyperactive spontaneous brain activity, overactive top-down feedback, and an overreliance on prior knowledge learned from past experiences.

To elucidate the neurobiological mechanisms of visual hallucination, we will study two distinct patient populations: those with ophthalmological conditions, including Charles Bonnet Syndrome (CBS), and those with neurodegenerative disorders, including Parkinson’s disease (PD) and dementia with Lewy body (DLB). In these conditions, the pathology lies either in the input pathways (CBS) or in the central brain (PD and DLB). The He Lab will integrate findings across patient groups to build a unified framework of the neurobiological underpinnings of visual hallucinations. Our long-term goal is to identify biomarkers and potential treatment targets for visual hallucinations across diseases to meet a major unmet clinical need.

The Influence of IFN Signaling on Astrocyte Function and Neuronal Vulnerability Following Ischemic Stroke

Principal investigators: Shane A. Liddelow, PhD, and Youssef Z. Wadghiri, PhD

Stroke is a leading cause of disability and the fifth leading cause of death in the United States. It is associated with neuron cell death, vascular damage, and infiltration of peripheral immune cells—all of which provoke central nervous system (CNS) inflammation. Neuron death is tightly regulated by neuroinflammation following the initial event, but also in the subacute and chronic phases—with many pathological hallmarks like glial scarring persisting for years. Despite their critical supportive role in normal brain homeostasis, microglia and astrocytes have been increasingly implicated in the progression of degeneration and worsening of many diseases. Understanding the altered functions of distinct substates of reactive astrocytes and their impact on neuronal vulnerability will pave the way for novel strategies to protect neurons following stroke and a number of other neurodegenerative and neurodevelopmental disorders.

One substate is strongly interferon (IFN)-responsive, which hints at an important immune regulatory role. We have modeled these IFN-Responsive Reactive Astrocytes (IRRAs) in vitro and found that they do not induce apoptosis in neuronal cultures. We will investigate whether IRRAs respond to peripheral signals to preserve brain homeostasis and maintain neuronal connectivity and function following stroke.

Central Pathways and Mechanisms of Glucose Regulation During Sleep

Principal investigators: Anli A. Liu, MD, and Gyorgy Buzsaki, MD, PhD

Diabetes, a chronic disorder of glucose regulation, affects 537 million people worldwide. Epidemiological studies reveal a strong association between sleep disturbance, obesity, and diabetes, but how one condition affects the other is poorly understood. Hippocampal sharp wave ripples (SWRs) have been extensively studied for their critical role in long-term memory consolidation. We seek to elucidate the brain circuitry involved in glucose regulation and investigate glucose fluctuations during sleep by comparing peripheral glucose fluctuations in relation to SWRs in surgical epilepsy patients. This will allow us to quantify how pathological interictal epileptiform discharges occurring between seizures may compete with SWRs to alter this relationship and help confirm the role of SWRs in glucose regulation while potentially identifying a novel brain-based biomarker for diabetes management.

Creation of a New Model System for Studying Autism-Related Communication Disorders

Principal investigator: Michael A. Long, PhD

Autism spectrum disorder is a neurodevelopmental condition affecting 1 in 31 people. Communication impairments are the core deficit of autism, negatively affecting the quality of life for autistic individuals and their caretakers. Yet despite its prevalence and detrimental impact, how autism affects the brain processes that enable social communication remains poorly understood. We seek to lay the groundwork for a new animal model to examine the link between autism-related neural changes and communication impairments. With the help of NYU Langone’s Advanced Rodent Transgenics Lab, we will create five such transgenic lines and examine the behavioral consequences of this manipulation on vocal behavior. This includes interactive turn-taking, an ability that is profoundly affected in autism but for which there is no existing animal model. In future studies, we will use these transgenics to investigate relevant neural mechanisms that are affected by autism as a means of spurring efforts for therapeutic interventions.

Deciphering the Role of the Microbiome in Parkinson’s Disease Pathogenesis

Principal investigators: Khalil Ramadi, PhD, and Thong C. Ma, PhD

The human gastrointestinal (GI) tract is densely populated by over 1,013 bacteria of various phyla, and they can have a huge impact on health. Dysbiosis has been linked to various neurological disorders such as Parkinson’s disease (PD). The GI microbiome is heterogeneous and varies significantly across the GI tract (GIT). Microbiome analyses are generally done through fecal sampling, which mostly represents luminal bacteria in the colon and does not reveal the full breadth of the microbiome along the GIT.

Other than endoscopic biopsy or postmortem histology, few techniques exist to interrogate bacteria in the small intestine and those adherent to the mucosa along the GIT. This is particularly significant in PD, as, for example, microbes in the small intestine may regulate the bioavailability and efficacy of levodopa, the gold standard therapeutic for symptomatic control. We aim to develop ingestible devices for comprehensive microbiome analysis to study the impact of α-synuclein pathology (which leads to PD) on the microbiome and use these findings to provide greater resolution of the bacterial species present and their alterations.

NYU MS Lifespan Data Initiative

Principal investigators: Kimberly A. O’Neill, MD; Rachel Kenney, PhD; and Els D. Fieremans, PhD

Healthcare data, especially in neurology, faces the classic challenges of “big data”: it is quantitatively large, qualitatively complex, and changes over time. Neurology relies heavily on clinical history, biomarkers, and neuroimaging, which can be more comprehensively analyzed with AI methods. Here we propose the infrastructure for AI research using available data to create an MS data registry to help better diagnose, prognosticate, and treat individuals living with MS. The creation of an MS registry will be enhanced with AI-powered tools such as brain volume assessment and tools to understand the degree of disability. This MS registry will be the template for other NYU Langone disease registries, including stroke, headache, and dementia. These methods will allow our researchers to better advance study of neurologic disease and provide high-quality care for those we treat.

Whole-Brain Optical Imaging of CSF Flow and Neurodegeneration-Related Protein Accumulation

Principal investigators: Shy Shoham, PhD, and Einar M. Sigurdsson, PhD

The glymphatic system—a brain-wide network responsible for clearing waste via cerebrospinal fluid (CSF) flow—may play a critical role in the development of numerous neurodegenerative and neurological diseases. Dysfunction of the glymphatic system has been linked to the accumulation of Alzheimer’s-related proteins, such as tau, which are strongly implicated in the progression of Alzheimer’s disease. Impaired glymphatic clearance is also associated with conditions such as brain vascular disease, epilepsy, traumatic brain injury, and stroke, making it a crucial area of study. Our goal is to develop cutting-edge, whole-brain imaging technologies to directly examine the relationship between glymphatic CSF flow and neurodegeneration-related protein accumulation. These tools will offer unprecedented precision, enabling us to uncover mechanisms of glymphatic dysfunction that were previously inaccessible, ultimately informing the development of novel diagnostic and therapeutic strategies to improve outcomes across multiple diseases.