Orly Lazarov, PhD, Professor - Program Director and Mentor
Molecular and cellular mechanisms underlying cognitive decline in normal aging and in AD. Particularly, the role of neurogenesis and hippocampal plasticity in learning and memory and its dysfunction in AD. That includes the examination of signals regulating learning and memory, mechanisms pporting neurogenesis in the adult brain, the molecular mechanism underlying impaired neurogenesis in Alzheimer's disease, the roles of familial Alzheimer's disease- linked proteins in regulation of neurogenesis and the role of impaired neurogenesis in cognitive failure and memory loss. A recent focus is the search for neurogenesis -based drug for cognitive failure in AD. In addition, research at the Lazarov lab examines the role of the environment in the development of ADRD, including type-2-diabetes and vascular factors.
Greg Thatcher, PhD, Professor - Co-Director and Mentor
Dr. Thatcher has multiple projects specifically directed at AD therapy are active (1) Nomethiazoles are designed to activate cGMP/CREB signaling, attenuate TNFa elevation, and provide neuroprotection via potentiation of GABAA activity. (2) Calpain/cathepsin B inhibitors as therapy in AD. (3) benzothiophene ER ligands to develop chemical probes to define mechanism of estrogen in EFAD mice. (4) TLR4 ligands, ACAT inhibitors, and RXR agonists to define dependence on APOE isoform (5) developed cell based assays to screen 10k compounds for selective ABCA1 agonists designed to increase levels of functional apoE4; analogue synthesis and validation in primary cells is in progress.
Theme 1: Basic Biology
Ernesto Bongarzone, PhD, Professor - Mentor
Proteopathies are a collection of adult-onset neurodegenerative conditions where abnormal folding of one or more proteins lead to neuronal and glial dysfunction. Alpha-synuclein (a-syn) is a small (~18 KDa) and soluble pre-synaptic protein of unknown function, and has an intrinsic tendency to form insoluble amyloid aggregates in a number of late onset proteopathies such as Parkinson's disease and multiple system atrophy. Dr. Bongarzone's overarching hypothesis is that a progressive albeit non-lethal deficiency in the homeostatic control of amyloidogenic proteins and sphingolipids by the lysosomal/autophagy pathway is a contributing factor to neuronal vulnerability in aging and adult-onset proteopathic neurodegeneration, including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis.
Marcelo Bonini, PhD, Associate Professor - Mentor
Dr. Bonini's research program focuses on determining if endothelial vascular dysfunction resulting from a chronic inflammatory state initiates or promotes hippocampal neuron deterioration and AD. The main hypothesis is that inflammation hinders the capacity of endothelial cells to transport insulin from the circulation to neural tissue depriving neurons of this critical trophic factor. Further, because hippocampal neurons are particularly dependent on insulin, AD-like syndromes are distinguished by and result from vascular endothelial dysfunction. Research examines the role of the caveolae-mediated transcytosis Caveolin-1 (Cav-1) in insulin transport in endothelial cells and in pathological type-2-diabetes and AD.
Scott Brady, PhD, Professor - Mentor
Dr. Brady's Research focuses on molecular motors, axonal transport and the neuronal cytoskeleton, Neuronal signaling pathways, Effects of myelin on neurons and pathogenic mechanisms in adult-onset neurodegenerative diseases including Alzheimer's disease, Parkinson's and Huntington's as well as amyotrophic lateral sclerosis and diabetic neuropathy.
Doug Feinstein, PhD, Professor - Mentor
Dr. Feinstein studies processes of neuroinflammation in the context of aging and neurodegenerative diseases particularly AD and MS. His work in the area of AD began when he showed that reduction of CNS noradrenaline (NA) levels following chemical lesion of the Locus coeruleus (LC), exacerbates cortical inflammatory responses to cytokines as well as to amyloid. He then showed that similar lesions increased neuropathology in transgenic mouse models of AD, including increases in amyloid burden, frank neurotoxicity, and worsening of behavioral deficits. Dr. Feinstein's findings therefore provide one of the few functional links between the LC damage that occurs in AD, and disease progression. Complementary studies have explored interventions to restore CNS NA levels.
Chris Janson, MD, PhD, Assistant Professor - Associate
Dr. Janson examines the role of physiological brain barriers in the pathogenesis of neurodegenerative diseases, stroke, and brain trauma. His research focus is on understanding transport processes at the arachnoid, choroid, and vascular membranes in Alzheimer's disease. Among other projects, his group is currently characterizing a new transgenic rat model of Alzheimer's on the structural and gene expression levels, to define the relative activity of each brain barrier component.
Mary Jo LaDu, PhD, Professor - Mentor
The role of structural and functional interactions between amyloid-β peptide (Aβ), considered a major cause of AD, and apolipoprotein E (apoE) in causing the APOE4-induced risk for AD. Additionally, APOE4-specific risk extends to recovery from head injury, cerebral hemorrhage stroke and other neurodegenerative diseases, including CAA. As a general mechanism, Dr. LaDu has demonstrated that APOE4 is associated with a pro-inflammatory state and an increase in neurotoxicity compared to APOE3, highlighting the potential for therapeutics that target the entire "at risk" APOE4 . The overall functional hypothesis is that APOE genotype-specific interactions with neurotoxic Aβ species form the basis for APOE4-induced AD risk.
John Larson, PhD, Associate Professor - Associate
Dr. Larson is the Director of Graduate Studies (DGS) of the Graduate Program in Neuroscience (GPN). Dr. Larson studies the cellular and molecular mechanisms of memory formation. Of primary interest is long-term potentiation (LTP), a form of synaptic plasticity thought to be responsible for memory storage in the mammalian forebrain. Research in his laboratory investigates the role of LTP in olfactory learning and memory in rodents, with emphasis on mouse models of autism, intellectual disability, and neurodegenerative diseases such as Alzheimer's disease. Dr. Larson's laboratory also studies neuronal specialization in the brains of naked mole-rats, in particular, tolerance of brain neurons to extreme oxygen deprivation.
Amy Lasek, PhD, Assistant Professor - Mentor
The research focus in Dr. Lasek's laboratory is to determine the mechanisms in the brain that underpin alcohol and drug abuse, causing neurodegeneration in areas of the brain important for learning and memory and cognitive functioning. Her research examines gene expression changes in the hippocampus after chronic alcohol consumption in rodents that lead to reduced dendritic arborization and spine density, loss of neurons, and overall volume shrinkage, resulting in depression-like behavior and deficits in learning and memory. Her group has identified changes in genes encoding extracellular matrix and neuroimmune factors that are likely detrimental to neurons. Degradation of the extracellular matrix and increased immune signaling in the brain is also associated with other neurodegenerative diseases such as Alzheimer's.
Loeb, Jeffrey, MD, PhD, Professor - Mentor
Dr. Loeb is the Head of Neurology at UIC. He is a practicing neurologist as well as a basic developmental neuroscientist with training in neuromuscular development. Combining human tissue functional genomic studies with an animal model, his research is aimed at finding overlapping drug targets that may have a greater chance of translating back to human therapeutics for epilepsy. In addition, he studies soluble forms of heparin-binding neuregulin forms. His group has developed a novel, targeted biopharmaceutical antagonist that will be brought to clinical trials. They have shown that this antagonist targets neuregulin signaling both in development in vivo as well as in a model of chronic pain after intrathecal injection. Dr. Loeb is the Director of the Repository Center at UIC.
Rich Minshall, PhD, Professor - Mentor
Dr. Minshall's research program focuses on understanding how structural and scaffolding functions of the endothelial protein caveolin-1 regulate formation and trafficking dynamics of caveolae, cell-cell communication, PMN adhesion and transmigration, and endothelial and epithelial cell proliferation and differentiation during inflammatory injury and repair/remodeling. He is also investigating G protein dependent signaling mechanisms in endothelial cells that regulate von Willbrand factor secretion associated with microvascular thrombosis and multi-organ system failure in sepsis. Using genetic in vivo and in vitro approaches, disease models, and human tissues, his lab is assessing the mechanisms by which caveolin-1 expression level and post-translational modification regulates vascular homeostasis in health and in pathology.
Subhash Pandey, PhD, Professor - Mentor
The long-term goal of Dr. Pandey's alcohol research program is to elucidate the molecular and synaptic mechanisms involved in anxiety and compromised cognitive function in alcohol addiction. Dr. Pandey's lab is involved in investigating the epigenetic mechanisms and discovering epigenetic marks (ChIP-seq) and gene expression profiling (RNA-seq) at the whole genome level to find novel epigenetically-regulated gene network pathways in specific brain circuitry using animal models and human post-mortem brain tissue. He is the Director of the NIH-supported Alcohol and Addiction Center at UIC.
Leon Tai, PhD, Assistant Professor - Associate
Dr. Tai's research examines the blood-nerve barrier, blood-spinal cord barrier and blood-brain barrier- specialized, dynamic and complex cellular barriers throughout the human body. These barrier interfaces play a central role in homeostasis and neuronal function, through preventing the uptake of unwanted molecules, removing waste products, supplying essential nutrients and signaling molecules, and modulating inflammation. His goal is to identify and therapeutically target mechanistic pathways that underlie barrier and neuronal dysfunction in aging and neurodegenerative disorders, particularly Alzheimer's disease, chronic pain, ALS and metabolic dysfunction.
Theme 2: Drug Discovery and Development
Leslie Aldrich, PhD, Assistant Professor - Associate
Dr. Aldrich investigates topics at the interface of synthetic chemistry and biology with a focus on human health and disease. The goal is to discover and optimize small molecules to probe complex biological pathways and potentially identify novel therapeutic mechanisms. In addition, to develop small molecules that target specific autophagy proteins or protein-protein interactions and to explore the role of these proteins and interactions in the autophagy pathway and in various disease states, including inflammatory diseases, infectious diseases, lysosomal storage diseases, neurodegenerative diseases and aging. Her group's experience in synthetic chemistry, medicinal chemistry, biochemistry, cell biology, and high-throughput/high-content assay development enables them to explore highly interdisciplinary research topics.
Stephanie Cologna, PhD, Assistant Professor - Associate
The Cologna laboratory at UIC is a mass spectrometry (MS)-based bioanalytical laboratory that works at the intersection of chemistry, molecular biology and human health. Current projects include developing assays to understand proteoform differences in genetic, neurodegenerative disorders, lipid mapping by mass spectrometry imaging in cerebellar degeneration, and protein biomarker discovery by MS. To complement the ongoing projects, members of the laboratory work to develop new methodologies and technologies to improve biomolecule detection by mass spectrometry. The overarching objective of the lab is to identify disease markers from disease specimens, investigate new pharmacological targets in signaling pathways and follow disease progression and therapeutic efficacy.
Stephen DiMagno, PhD, Professor - Associate
Dr. DiMagno's research group focuses on the preparation and validation of 18F-fluorinated PET and 123I-iodinated SPECT radiotracers for imaging human disease state. He has developed a general synthetic methodology, based upon the unique chemistry of diaryliodonium salt precursors that enables a wide variety of aromatic compounds to be fluorinated and iodinated readily. His research is focused on developing brain penetrating radiotracers aimed at imaging downstream biomarkers in AD pathology, such as filamentious Tau and neuroinflammation. To date, two promising tracers (T-807, T-808) have been developed for imaging Tau neurofibrillary tangles. His research is aimed at developing efficient radiosyntheses of previously validated and/or potentially new neuroimaging biomarkers for the analysis of AD progression.
Terry Moore, PhD, Assistant Professor - Associate
Research in the Moore Lab focuses on developing small molecules and peptides that modulate transcription factor activity. His research group has an ongoing interest in the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Nrf2 is the major transcription factor for detoxification enzymes that protect against oxidative and electrophilic stress. There is a substantial body of work that suggests that activation of Nrf2 may protect from neurodegeneration that results from oxidative stress. His laboratory is creating non-covalent, pharmacological Nrf2 activators, and these may eventually find utility as therapeutics for Alzheimer's and other neurodegenerative conditions.
Pavel (Pasha) Petukhov, PhD, Professor - Mentor
Dr. Petukhov's research focuses on the development of new methods and biologically orthogonal chemical tools for chemical biology and drug discovery. He is specifically interested in applying chemical probes in epigenomics research and structure-, ligand-, and fragment-based drug design. Epigenomics - photoreactive histone deacetylase probes and inhibitors. Histone deacetylases (HDACs) are implicated in ADRD. He is interested in the development of isoform-selective HDAC inhibitors that would reduce off-target effects of HDAC-based therapeutics. The focus is on the design of photoreactive probes, liquid chromatography-tandem mass-spectrometry, and molecular dynamics simulations to map the ensemble of the poses of HDAC inhibitors upon binding or BEProFL - (B)inding (E)nsemble (Pro)filing with (F)photoaffinity (L)abeling.
Theme 3: : Clinical and Translational Research
Neelum Aggarwal, MD, Associate Professor - Associate
Dr. Aggarwal is a Co-Investigator/Senior Neurologist on multiple NIH-funded studies at the Rush Center. She is a Senior Examining Neurologist for the Clinical Core of the NIA funded Rush Alzheimer's Disease Center (ADC), the Neurologist for the MIND Diet Intervention to Prevent Alzheimer's Disease Study, Site PI of the NIA funded Alzheimer's Disease Cooperative Study Group (ADCS) and ATRI studies and Co Principal Investigator for the PCORI disparities funded Community Engagement for Early Recognition and Immediate Action in Stroke (CEERIAS) grant. She serves on the Steering Committee representing Rush for the innovative Alzheimer's disease Clinical Trials Consortium (ACTC) and will be able to facilitate cross institutional education and training activities surrounding the basic science and research in clinical trial development.
Olu Ajilore, PhD, Associate Professor - Mentor
The goal of Dr. Ajilore's research is to understand the pathophysiology of depressive disorder in the context of medical co-morbidities and late life using novel magnetic resonance imaging techniques. His group focuses on using structural and functional brain connectivity to study the brain as a network. Using these modalities, they have developed innovative ways of discovering brain changes associated with major depression that may lead to patient-specific targets for intervention and treatment. Through these research projects, trainees can learn about neuroimaging methods such as functional magnetic resonance imaging, diffusion tensor imaging, and magnetic resonance spectroscopy acquiring skills in image acquisition, pre-processing, computational modeling and data analysis.
David Bennett, MD, Professor (Rush University) - Associate
Dr. David A. Bennett is the Director of the Rush Alzheimer's Disease Core Center and Principal Investigator (PI) of the Religious Orders Study and the Rush Memory and Aging Project. Together, these studies collect detailed data on cognitive function annually on more than 3,300 persons across the country. He is the Principal- or Co-Investigator of numerous omics studies including genome-, epigenome-, transcriptome-, proteome-, and metabolome-wide association studies with data generated from human brain tissue, peripheral blood mononuclear cells, and iPSC lines generated from his participants. Dr. Bennett is also PI of a genomic study of ancestry and neurodegenerative disease at the University of Sao Paulo. He has published many manuscripts linking experiential, medical risk factors, transcriptomic data to aging and dementia.
Patricia Boyle, PhD, Associate Professor (Rush University) - Associate
Dr. Boyle's research focuses on the neurobiologic basis of age-related changes in cognitive function and the role of potentially modifiable factors that protect against cognitive and functional decline in old age. This research utilizes the unique data collected by the Rush Alzheimer's Disease Center and other Rush-based studies and has shown that decline in cognition is common but not inevitable in old age, and that psychological and experiential factors protect against decline. Dr. Boyle has shown that the three most common neuropathologic causes of dementia, Alzheimer's disease, cerebrovascular disease, and Lewy body disease, are important determinants of cognitive decline but much of the variability in cognitive decline remains unexplained by these indices.
Jacob Haus, PhD, Associate Professor - Mentor
The Haus Lab studies mechanisms of obesity, insulin resistance and diabetes and how exercise and diet can reverse or prevent these conditions. Current areas of focus involve hyperglycemia induced protein glycation, and the path from diabetes to Alzheimer's disease. The overarching hypothesize is that both exercise and diet have beneficial effects on reversing advanced glycation in human tissues. The hypothesis is tested in human subjects by performing procedures that will determine how sensitive the body is to insulin and by taking a biopsy of muscle and adipose tissues. Stable isotope tracers are used to study metabolic pathways in the human body non-invasively. This will allow the validation of early treatments for diabetes that will prevent or treat long-term complications associated with diabetes, such as cognitive decline.
Susan Hughes, PhD, Professor - Associate
Dr. Hughes directs the Center for Research on Health and Aging at UIC. She is currently Principal Investigator of the National Institute on Aging Midwest Roybal Center for Health Promotion and Translation (P30) which is her fourth consecutive Roybal Center grant. The Center focuses on the design, testing, and translation of evidence-based health promotion programs for older adults with an emphasis on cognitive health. Dr. Hughes is also the originator of Fit and Strong! (FS), an evidence-based physical activity/behavior change program for older adults with lower extremity osteoarthritis (OA). FS is based on findings from a 4-year longitudinal study of 600 older adults that she conducted in the 1990s with funding from NIAMS/NIH. Her work is characterized by a strong commitment to the use of interdisciplinary teams to conduct community- based interventions.
Pauline Maki, PhD, Professor - Mentor
Dr. Maki has directed a program of NIH-funded research on women's cognitive aging and dementia, with a particular focus on the menopause. She studied the effects of hormone therapy and alternative treatments for menopausal symptoms on cognition and brain function in women. Two recent R01s focus on whether women with vasomotor symptoms might benefit from hormone therapy. As multi-PI in an NIA-funded R01, she is now examining the relationship between vasomotor symptoms, cognition and brain function, as her preliminary work shows that objectively measured hot flashes are associated with poor memory, white matter hyperintensities and alterations in the resting state network. In another NIA-funded R01, she is co-investigator on a randomized clinical trial examining a novel intervention for vasomotor symptoms.
Laura Pedelty, MD, PhD, Associate Professor - Associate
Dr. Pedelty is the chief of Neurobehavior and the Director of the Memory and Aging clinic at UIC. Her combined subspecialty expertise is in Behavioral Neurology and Vascular Neurology. Dr. Pedelty's clinical and research interests have focused on the interface between vascular disease and dementia and their common risk factors. Clinically, she has extensive expertise in diagnosing and treating patients with dementia, across a spectrum of severity. Our Memory and Aging (MAC) and Vascular Cognitive Impairment and Dementia and Memory Disorders (VCI/M) clinics assess approximately 300 new patients annually, and follow over a thousand dementia patients longitudinally. Her interdisciplinary staff comprises a team of neurologists, psychiatrists, geriatricians, neuropsychologists, social workers, and community liaisons.
Neil Pliskin, PhD, Professor - Associate
Dr. Neil Pliskin is a board certified clinical neuropsychologist and Professor of Clinical Psychiatry and Neurology at the University of Illinois College of Medicine. He has worked as a clinical neuropsychologist and directed Clinical Neuropsychology training programs for over 28 years. Dr. Pliskin has strong scientific interests in the neuropsychological sequelae of dementia and brain trauma. He has contributed to the care of hundreds of patients with primary degenerative dementias. Dr. Pliskin has collaborated on numerous research investigations over his career addressing cognitive impairment in older adults.
Julie Schneider, MD, Professor (Rush University) - Associate
Dr. Julie A. Schneider is senior neuropathologist of the Rush Memory and Aging Project. She is also the senior neuropathologist of Rush Religious Orders Study, and the Clinical Core and Latino Core of the Rush ADCC (P30AG010161), and the senior neuropathologist for the Rush Minority Aging Research Study (RF1AG022018). She oversees the autopsies, biospecimen collection, storage, and distribution, brain dissections and quantification of pathologic indices, and neuropathologic diagnostic assessments. She has extensive experience collaborating on translational science as evidenced from publications spanning neuropathology, clinical neurology, basic science, genetics, and neuroimaging. Dr. Schneider's current focus is on the cognitive sequelae of mixed pathologies and the role of vascular pathologies and TDP-43 in aging.
Raj Shah, MD, Associate Professor (Rush University) - Associate
Dr. Raj Shah's academic career interest is the design and conduct of community-based, clinical trials for the prevention and treatment of age-related conditions including, but not limited to, memory loss, affecting diverse populations of older adults. Along with conducting research looking at modifiable risk factors for physical and cognitive decline in older persons using data from the Rush Religious Orders Study, the Rush Memory Aging Project, and the Rush Minority Aging Research Study, he has led to the successful design and completion of an investigator initiated community based intervention trial in older individuals with memory concerns, has been United States Co-Investigator of a multicenter clinical trial of a food for the treatment of Alzheimer's disease, and a Co-Investigator in NIA-supported ASPirin in Reducing Events in the Elderly (ASPREE).
Rita Shapiro, DO, FAAN, FACP, Associate Professor - Associate
Dr. Shapiro has extensive experience in clinical care, education and collaborative research for neurocognitive disorders. She initiated multi-disciplinary memory clinics and dementia committees at Jesse Brown VAMC, Hines VA and Lovell FHCC (former North Chicago VAMC) beginning in 1990. Currently she is involved in clinical care, education of residents and fellows and research at the Memory and Aging Clinic (MAC@UIC) as well as general neurology clinic at the University of Illinois at Chicago and Jesse Brown VAMC, working closely with geriatrics, psychiatry and neuropsychology. Patients and families visiting the MAC are eligible to be involved in current and future approved research studies.
Woojin Song, PhD, Assistant Professor - Associate
As a clinical neuropsychologist, Dr. Song has been working with patients with Alzheimer's disease and other types of neurodegenerative conditions in various settings, including inpatient, general outpatient and specialty clinics such as Memory and Aging Clinic. Typically, she evaluates patients' cognitive functioning and characterizes their decline in various cognitive domains such as memory, attention, executive functioning, language, and visuospatial skills using standardized neuropsychological measures. In addition, she conducts evaluations of social, personality, emotional and functional changes using interviews and standardized questionnaires. Her clinical evaluations are usually conducted in response to consults of referring physicians, commonly neurologists, geriatricians or psychiatrists.
Theme 4: Biophysics, Bioinformatics and Data Science
Andy Johnson, PhD, Associate Professor - Mentor
Dr. Johnson's work for the last 20 years has focused on the effective use of advanced visualization displays for research and education, combining areas of visualization, human-computer interaction, and collaboration. This involves the design, implementation, and commercialization of new visualization displays and the software to run them, as well as working closely with domain scientists and educators to create applications that run on these displays, and then studying those users to see where the next set of opportunities for improving in the hardware and software lie.
Dietter Klatt, PhD, Assistant Professor - Associate
The Klatt lab focuses on the refinement and application of elasticity-based diagnostic imaging techniques using MRI. Magnetic Resonance Elastography (MRE) is capable of measuring diagnostically relevant tissue stiffness non-invasively. Recent studies indicate that in Alzheimer's disease and related neurodegenerative diseases, the loss of functional connectivity involves a loss of mechanical connectivity, which can be measured using MRE. The Klatt Lab has improved accuracy and acquisition speed of MRE elastograms by engineering alternative motion encoding concepts that are capable of simultaneously acquiring multidirectional, multifrequency displacement data. Currently sensitivity and effectiveness of MRE measurements in mouse models of Alzheimer's disease, are being assessed by a comparative analysis of disease progression.
James Lee, PhD, Associate Professor - Mentor
The mission of Lee's research program is to apply biophysical engineering principles and techniques to investigate the roles of membrane and cell mechanics in the pathology of Alzheimer's disease (AD) including oxidative stress, inflammation, amyloid-β clearance, amyloidogenesis, and alterations in blood brain barrier. Specifically, Lee focuses on mechanical properties (nN to pN scale), molecular packing and molecular organization (~nm) of membranes, cytoskeleton and their components in neuronal and microvascular cells in the central nervous system. Various nano-mechanical characterizations, microscopic and spectroscopic, photonic, cell manipulation techniques, including atomic force microscopy, micropipette cell manipulation and aspiration, beam splitter, and laser are employed in both his basic biomedical and clinical research projects.
Jie Liang, PhD, Professor - Mentor
The research in Dr. Liang's lab ranges from molecules, interactions, networks, cells, and tissue. Recent work includes membrane protein structure and function prediction, pseudoknotted RNA, protein-protein interactions, engineering of bionanopores, biased path sampling of stochastic network, numerical solution of chemical master equation, epigenetic probability landscape of cells, 3D chromosome folding, and dynamic discrete cell models for tissue pattern formation. Dr. Liang is the Director of the Bioinformatics graduate program.
Xincheng Yao, PhD, Professor - Mentor
Dr. Yao directs the Biomedical Optics and Functional Imaging Laboratory focused on optical technology for advanced imaging of the retina, neural tissues and endocrine cells. Two major projects are the functional intrinsic optical signal (IOS) imaging of retinal physiology and super-resolution ophthalmoscopy (SRO) of retinal morphology. The functional IOS study is to investigate endogenous optical biomarkers correlated with retinal physiological dynamics and dysfunction. This effort will layout the necessary foundation to develop new instruments for functional evaluation of retinal physiological condition at unprecedented resolution. The SRO project uses virtually structured detection (VSD) to pursue resolution-doubling in retinal ophthalmoscopy. This will reveal subtle distortions in retinal morphology at early stage of eye diseases or pathology.