Active Research Projects

In addition to our Research Priorities and Projects at the Nappi Longevity Institute, this list highlights and is inclusive of all Alzheimer’s and Other Dementia Related Research conducted at Upstate Medical University by department as well as Neurodegenerative Disease Related Research

Research by Department:

Biochemistry and Molecular Biology
Geriatrics
Microbiology and Immunology
Neurology
Neuroscience and Physiology
Neurosurgery
Ophthalmology and Visual Sciences
Physical Therapy
Psychiatry
Psychiatry and Behavioral Sciences

Biochemistry and Molecular Biology

Xin Jie Chen, Professor

Mechanism of mitochondria-induced progressive muscle wasting, $1,983,480, RO1AG061204, National Institute on Aging/NIH, 1/1/2019-11/30/2023
Alzheimer’s disease and mild cognitive impairment (MCI) are major and growing public health problems, imposing tremendous costs at personal, social, and institutional levels. One strategy for combating these disorders is to improve our ability to detect their presence or predict their emergence, so that earlier interventions can be developed, by discovering objective, laboratory-based biomarkers.

This project seeks to identify blood-based gene-expression biomarkers of MCI within the context of an ongoing longitudinal study of middle to early old-age twins, which will help us understand to what degree the molecular correlates or precursors of MCI are influenced by genetic and environmental factors, as well as the biological processes that may underlie this condition.

Mechanism of age-dependent neuromuscular degeneration caused by protein misfolding on the inner mitochondrial membrane, $196,069, F30AG060702, National Institute on Aging/NIH, 8/30/2018-8/29/2022
This is a predoctoral fellowship grant for Liam Coyne, focusing on the mechanism of neural and muscular diseases caused by mutations in Ant1, an ATP/ADP translocase localized on the inner mitochondrial membrane.

Role of Mitochondrial Proteostatic Signaling in Neurodegeneration, $50,000, Pilot Research Grant, Upstate Foundation, 7/1/2019-6/30/2020
The goal of this project is to test the hypothesis that mitochondria-induced proteostatic stress modulates the pathogenesis of Lewy body dementia.

Microbiology and Immunology

William Kerr, Professor

Translating SHIP1 Genetics to Generate a Novel Alzheimer’s Pharmacologic Agent, Variants in the DNA that we inherit from our parents constitutes about 70% of the risk of Alzheimer's disease. Here, we will determine how one of these variants, in a gene called INPP5D, acts to increase AD risk, and test whether an inhibitor of SHIP1, the protein produced from INPP5D, reduces AD risk.

Overall, our goal is to turn genetic findings into pharmacologic approaches to reduce the risk of Alzheimer's disease.

Neurology  

Karen Albright, Assistant Professor

Personalized Antiplatelet Secondary Stroke PRevenTion (PASSPoRT). A Randomized, Phase II, Open Label, Trial in High Risk Transient Ischemic Attack (TIA) and Ischemic Stroke Survivors Age 18 Years and Older

An Innovative Laboratory Test for Predicting Reocclusion and Poor Outcomes in Neuro-Interventional Patients

Anuradha Duleep, Associate Professor, Medical Director, Division Chief

RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED, DOSE-RANGING STUDY OF PIROMELATINE IN PATIENTS WITH MILD DEMENTIA DUE TO ALZHEIMER’S DISEASE

The association between Autonomic dysfunction in patients with cryptogenic stroke and development of atrial fibrillation.

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Julius Gene Latorre, Professor

Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) Trial

AWARE II (AWAreness during REsuscitation)- A Multi-Centre Observational Study of the Relationship between the Quality of Brain Resuscitation, Consciousness, Neurological, Functional and Cognitive Outcomes following Cardiac Arrest

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema following Large Hemispheric Infarction

Multi-arm Optimization of Stroke Thrombolysis (MOST): a blinded, randomized controlled adaptive, multi-arm, adjunctive-thrombolysis efficacy trial in ischemic stroke

Sleep SMART: Sleep for Stroke Management And Recovery Trial

Luis Mejico, Professor and Chair

A Phase 2/3, Randomized, Double-Masked, Sham-Controlled Trial Of QPI-1007 Delivered By Single Or Multi-Dose Intravitreal Injection(s) To Subjects With Acute Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)

Effect of Erenumab-aooe on Disability and Work Productivity in Employed Subjects With Episodic Migraine Who Have Previously Failed 1 or More Migraine Preventive Treatments

Dragos Mihalia, Professor

A Phase 3, Twelve-week, Multi-Center, Multinational, Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Determine the Efficacy, Safety and Tolerability of P2B001 Once Daily Compared to its Individual Components in Subjects With Early Parkinson’s Disease and to a Calibration Arm of Pramipexole ER

Eufrosina Young, Assistant Professor

Cognitive Navigation: An Eye-Tracking Analysis Instrument for the Measurement of Cognitive and Behavioral Abilities in ALS Patients

Neuroscience and Physiology

Frank Middleton, Associate Professor
co-I: Sharon Brangman, MD, Chair, Department of Geriatrics

Development and Characterization of Salivary miRNA Biomarkers for Lewy Body Dementia and their Relationship to Pesticide Exposures, $30,000, SUNY Institute for Global Health and Translational Science Center for Environmental Health and Medicine Pilot Award, 10/2019-9/2020
This study identifies changes in salivary noncoding RNA content that occur in subjects with Lewy Body Dementia, and compares them to controls and subjects with Parkinson’s disease, in whom pesticide exposures have been well-defined.

In vitro experiments are also being performed to model the exposure effects.

Molecular and functional biomarkers of Parkinson's disease

Huaiyu Hu, Professor

Role of myosin VIIa in Usher Syndrome, $324,000, R21EY031119, NIH/NEI, 8/1/2019-7/31/2020
This research is relevant to public health because Usher syndrome is a genetic disease that causes blindness through degeneration of the retina as well as hearing loss.

The goal of this project is to generate a primate model of Usher syndrome type I for testing experimental therapeutics to restore vision.

Mechanisms of cognitive deficits in dystroglycanopathies, $2,800,000, R01HD083860, NIH/NICHD, 4/3/2015-1/31/2020
Congenital muscular dystrophies with central nervous system involvement are devastating diseases with no effective therapy.

This project aims to study the mechanisms of brain dysfunction and develop an experimental gene therapy by using adeno-associated serotype 9 viral vectors to improve brain function.

Ciliary Pocket Matrix in photoreceptor health, $810,000, R01EY028555, NIH/NEI, 8/1/2019-4/30/2023
This research is relevant to public health because retinitis pigmentosa 25 is a genetic disease that causes blindness through degeneration of the retina. Numerous G protein coupled receptors (GPCRs), neuronal signaling proteins that are essential to cognitive function, are implicated in Alzheimer’s Disease.

The goal is to determine the mechanism of photoreceptor degeneration that will be essential to identify potential targets to prevent the loss of sight.

Neurosurgery

Zulma Tovar-Spinoza

Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate® System (LAANTERN) Prospective Registry

Li-Ru Zhao, Professor

Targeting the hematopoietic system: the role of hematopoietic growth factors in restricting A-beta accumulation in Alzheimer’s disease
This study highlights an important but less-investigated research field, the hematopoietic system---a system that generates scavenger cells for robust removal of amyloid-beta deposits in the brain is impaired in Alzheimer's patients. We have recently discovered a unique approach to repair the hematopoietic system.

The mechanistic understanding how this approach restricts amyloid-beta accumulation in the brain will facilitate the development of a new therapy for treatment of Alzheimer's disease.

Ophthalmology and Visual Sciences

Audrey Bernstein, Associate Professor

The Ubiquitin Pathway in Corneal Scarring, $1,700,000, R01EY024942, NIH/NEI, 8/1/2015-6/30/2023 
Worldwide, corneal scars are the leading cause of monocular blindness. Initial wound healing responses prevent infection but subsequent tissue repair must result in transparency to promote clear vision.

Our proposed research will reveal new pathways that can be targeted to prevent corneal scarring.

William J. Brunken, Professor and Vice Chair

Role of Extracellular Matrix in Retinal Development and Disease, $6,700,000, R01EY01676, NIH/NEI, 8/1/2000-3/31/2020
The extracellular matrix (ECM) surrounds cells providing them with environmental signals during development and stabile substrates for attachment and migration throughout life. Many human diseases are caused by disruptions of the ECM including metastatic cancer, proliferative neo-vascular disease, acquired auto-immune diseases, glaucoma and congenital birth defects. Many of the latter affect eye and brain and lead to impaired vision or blindness with mental retardation.

This project investigates the role of ECM in retinal development and the results of these studies will lead to new diagnostics for ocular disease, both genetic and acquired, and will lead to the development of new therapeutics. Also important is that the molecules regulate the activity of glial cells in the brain (cortex and retina) that perform important supportive functions for neurons.  Their dysfunction leads to neuronal loss like that seen in AZ and other neurodegenerative diseases.  

Peter Calvert, Professor

Construction and stability of photoreceptor outer segment discs, $884,000, R01EY028303, NIH/NEI, 4/1/2018-1/1/2023
This work seeks to understand the molecular mechanisms of retinal photoreceptor assembly and function. Retinal degeneration and blindness may be caused by improper construction of photoreceptors, the light detecting cells in our eyes. Numerous G protein coupled receptors (GPCRs), neuronal signaling proteins that are essential to cognitive function, are implicated in Alzheimer’s Disease.

Understanding the mechanisms that control photoreceptor construction, and what goes wrong with this process in blinding diseases, will help find new therapies to extend or restore vision.

Mechanisms of signal-dependent photoreceptor protein localization transport, $3,500,500, R01EY028303, NIH/NEI, 7/1/2020-6/30/2025 [Renewal Pending]
This work seeks to understand the molecular mechanisms of retinal photoreceptor function in health and disease. Retinal degeneration and blindness may be caused by improper delivery of key proteins to the cells in the eye that detect light.

Numerous G protein coupled receptors (GPCRs), neuronal signaling proteins that are essential to cognitive function, are implicated in Alzheimer’s Disease. Understanding the mechanisms that control this delivery, and what goes wrong in blinding diseases, will help find new therapies to extend or restore vision.

Robert Fechtner, Professor and Chair

Relationship of depression in glaucoma patients with level of medication adherence, and how depression may relate to self-reported visual function and clinical measures

The Biology of Ocular Tissues

Sleep Disorders in People with Chronic Stroke: Impact Across the International Classification of Functioning, Disability and Health

Preethi Ganapathy, Assistant Professor

Detection of Optic Nerve Surface and Lamina Cribrosa changes associated with transient elevations in IOP using Ocular Coherence Tomography (OCT).

Physical Therapy

George Fulk, Professor and Chair

Sleep Disorders in People with Chronic Stroke: Impact Across the International Classification of Functioning, Disability and Health

Bokkyu Kim, Assistant Professor

Kinematic analysis of compensatory movement strategies in chronic stroke survivors

Transcranial photobiomodulation therapy – illumining the brain to enhance motor skill learning in chronic stroke survivors: a preliminary pilot study

Christopher Neville, Associate Professor

Prospective Cohort study of ClearEdge Assessment system and saliva biomarkers in concussion injury

Targeted testing of an ankle balance brace and novel balance assessment in subjects with Parkinson's disease

Patient Reported Outcomes using the PROMIS scales: a focus on Concussion Injury

Psychiatry    

Wei-Dong Yao, Professor

Prefrontal AMPA receptors in FTD Pathogenesis
The goals of this R01 are to establish that prefrontal AMPA receptor dysfunction represents a pathogenic mechanism underlying social behavioral deficits of frontotemporal dementia.

The studies will establish a synaptic basis for social behavior, they advance our understanding of pathogenesis basis of FTD at molecular, synaptic, and circuit levels, and they provide new molecular targets and strategies for treatment of FTD.

 
Prefrontal cellular and circuitry mechanisms in a mouse model of C9ORF72-associated frontotemporal dementia, Frontotemporal dementia (FTD), the second leading type of dementia after Alzheimer’s, is a fatal, incurable neurodegenerative disease, affecting nearly 50,000-60,000 Americans; the underlying neural mechanisms are largely unknown.

This study utilizes a mouse model of C9ORF72-associated FTD, the most common familial type, and a combination of electrophysiological, chemogenetic, optogenetic and behavioral approaches to elucidate the cellular and circuitry mechanisms of behavior deficits associated with FTD. Successful completion of the project will have the potential to identify novel cellular targets for therapeutic interventions.

Psychiatry and Behavioral Sciences

Stephen J. Glatt Associate Professor

Expression Biomarkers for Early Identification of Mild Cognitive Impairment: A Twin Study, $2,686,736, R01AG054002, NIH/NIA, 9/15/2016-4/30/2020, co-PI: Ming T. Tsuang (University of California San Diego)
Alzheimer’s disease and mild cognitive impairment (MCI) are major and growing public health problems, imposing tremendous costs at personal, social, and institutional levels. One strategy for combating these disorders is to improve our ability to detect their presence or predict their emergence, so that earlier interventions can be developed, by discovering objective, laboratory-based biomarkers.

This project seeks to identify blood-based gene-expression biomarkers of MCI within the context of an ongoing longitudinal study of middle to early old-age twins, which will help us understand to what degree the molecular correlates or precursors of MCI are influenced by genetic and environmental factors, as well as the biological processes that may underlie this condition.

Richard Servatius, Professor

Balance, Physiological Reactivity and Neuropsychological Function Following Pediatric Traumatic Brain Injury