Derek Denny-Brown Young Neurological Scholar Symposium*

Date/Time: Monday, September 11, 2023 - 1:15 PM – 3:45 PM
Track: Plenary
Room: Salons E-F (5th Floor)
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Chair: Laurie Gutmann, MD, FANA

Co-Chair: Richa Tripathi, MD

The Derek Denny-Brown Young Neurological Scholar Symposium is an opportunity for young researchers to share groundbreaking research in the field of Neurology and Neuroscience. This symposium will feature presentations from the 2023 Derek Denny-Brown awardees, the Grass Foundation-ANA Award in Neuroscience recipients, and the Audrey S. Penn Lectureship awardee. Awardees receiving the Distinguished Teacher Award, the ANA-Persyst IDEAS Professional Development Award, and the ANA Awards for Excellence will also be recognized during this session.

The Grass Foundation-ANA Award in Neuroscience

Award Recipient Yvette Wong, PhD, Northwestern University Feinberg School of Medicine

Inter-Organelle Contact Site Misregulation in Neurodegenerative Diseases

Inter-organelle contact sites represent key pathways for different organelles to interact with one another, and allow for the bidirectional regulation of organelle function and dynamics. These include contacts that have been shown to dynamically form between mitochondria and lysosomes, which result in the direct modulation of both mitochondrial network dynamics and lysosomal network dynamics by one another. Mitochondria-lysosome contact sites are further misregulated at different steps in various diseases including Parkinson’s disease and Charcot-Marie-Tooth disease. Moreover, misregulation of additional inter-organelle contact site dynamics may be critical drivers of the pathogenesis underlying multiple other neurodegenerative diseases, such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS). Thus, further insights into organelle contact site dynamics and regulation using live super-resolution microscopy approaches will shed important light on the etiology mediating neurodegeneration.

Audrey S. Penn Lectureship

Award Recipient: Roy Hamilton, MD, MS, FANA, University of Pennsylvania

From Agnosia to Action: Moving Toward Diversity, Inclusion, and Equity in Neurology

Although the most common, serious neurologic disorders disproportionately affect marginalized and minoritized populations, the field of neurology has historically rarely been portrayed as having a special obligation to engage with persons from underserved and disadvantaged communities. One cause and consequence of this inattention to health equity may by the relative paucity of persons who hail from minoritized racial and ethnic groups who are drawn to careers in neurology. As patient populations in the US and elsewhere continue to become more heterogenous, diversity in the neurology workforce is increasingly essential to the delivery of culturally competent care and the ability to conduct inclusive, generalizable clinical research. Unfortunately, there are formidable challenges to achieving diversity in the neurology workforce, including an inadequate pipeline of trainees entering the field, explicit and implicit biases experienced by minoritized trainees and faculty, and “diversity tax,” the disproportionate burden of service work placed on minoritized persons in many professions. In this session, Dr. Hamilton—Professor and Vice Chair for Inclusion and Diversity in the Department of Neurology at the University of Pennsylvania, former Assistant Dean of Cultural Affairs and Diversity for the Perelman School of Medicine, and inaugural Associate Editor for Equity, Diversity and Inclusion for the journal Neurology and its associated journals—will discuss ways in which diversity enhances the clinical, educational, and scientific missions of neurology. He will characterize the barriers that impede the advancement of diversity, equity, and inclusion within the field of neurology. Lastly, based on lessons learned in the course of developing the Diversity, Inclusion, Anti-Racism, and Equity (IDARE) program in the Department of Neurology at the University of Pennsylvania, Dr. Hamilton will identify practical steps that can be taken by academic neurology departments and the field of neurology more broadly to reduce these barriers, in order to create a more diverse, inclusive, and equitable field.

Derek Denny-Brown Young Neurological Scholar Award - Basic Science

Award Recipient: Vikram Khurana, MD, PhD, Brigham & Women’s Hospital and Harvard Medical School

The Systems Cell Biology of Neurodegeneration: Proteins to Stem Cells to Patients

Our lab has generated and explored “proteinopathy maps.” These are integrative networks that depict changes in the cellular proteome as aggregation-prone proteins misfold. To generate these maps, genetic modifiers of proteotoxicities are integrated with protein-protein interaction data and local protein phase-transitions. Our first maps focused on the protein alpha-synuclein (Syn), a protein that aggregates in synucleinopathies including Parkinson’s disease (PD). These maps tied Syn through defined molecular interactions to numerous other PD genes and directly connected it to perturbed vesicle trafficking and mRNA metabolism. Our follow-up studies have demonstrated the utility of such maps in understanding disease pathogenesis and motivating therapeutics. First, we have discovered new functions for aggregation-prone proteins of relevance to disease. For example, we recently showed that the N-terminus of Syn dichotomously interacts with membranes and P-bodies, membraneless organelles involved in mRNA stability and gene regulation. Second, by integrating our maps with phenotypic screens of small-molecule probes, we have identified druggable targets, including a novel lipid metabolism target for Parkinson’s disease, stearoyl-coA desaturase. Third, our proteinopathy maps have shed light on the genetic architecture of synucleinopathies and factors that underlie the heterogeneity of disease risk and progression. Technical innovation in statistical genetics, AI and population-scale stem-cell modeling enable patient stratification and validation of molecular subtypes “in the dish.” The integration of proteinopathy mapping with deep phenotyping, genome-sequencing and stem-cell modeling thus offers a viable path toward targeted therapeutics for heterogeneous neurodegenerative diseases. To this end, our center is establishing a clinical-trials unit in which iPSC models of deeply genotyped and phenotyped patients will be utilized to match patients to appropriate therapies, and to test those therapies in longitudinal observational/interventional trials.

Derek Denny-Brown Young Neurological Scholar Award - Clinical Science

Award Recipient: Andrea Schneider, MD, PhD, University of Pennsylvania

Associations of Traumatic Brain Injury with Long-Term Outcomes: Insights from Epidemiologic Studies

Traumatic brain injury (TBI) is common and is associated with significant morbidity and mortality, especially among older individuals. Approximately 15.7% of U.S. adults aged 40 years or older have experienced a head injury with loss of consciousness, which amounts to approximately 23 million affected individuals. The current epidemiology of traumatic brain injury will be presented in this presentation. In addition, efforts focused on improving the characterization of the lifetime history of TBI in ongoing prospective cohort studies in diverse populations will be presented. Leveraging data with over 25 years of follow-up, studies presented herein will quantify the population-level burden of TBI and the dose-dependent long-term consequences of TBI (including data on cognitive decline, dementia risk, and mortality, among other outcomes) in a comprehensive manner. Data will also be presented showing how epidemiological study design and biostatistical methods can provide insights into mechanisms underlying observed associations. The robust and dose-dependent associations of TBI with adverse outcomes underscore the importance of public health measures aimed at preventing head injuries and targeted clinical interventions to reduce morbidity and mortality after head injury.

Derek Denny-Brown Young Neurological Scholar Award - Neuroscientist

Award Recipient: David Gate, PhD, Northwestern University

Genomic Approaches to Study Alzheimer's Disease Immunity

This presentation will cover recent findings from the Gate lab which identified a novel adaptive immune phenotype in Alzheimer's disease. The presentation will discuss Dr. Gate's use of novel genomic approaches to uncover mechanisms of T cell brain entry. Dr. Gate will also discuss the application of spatial transcriptomics to interpret mechanisms of amyloid clearance in post-mortem tissues from clinical trials for Alzheimer's disease.

ANA-Persyst IDEAS Professional Development Award

Award Recipient: Tanya J. W. McDonald, MD, PhD, Johns Hopkins University School of Medicine

ANA Award for Scientific Excellence 

Award Recipient: Michael Wilson, MD, MAS, FANA, University of California, San Francisco

ANA Award for Excellence in Education 

Award Recipient: Steven Lewis, MD, FANA, Lehigh Valley Fleming Neuroscience Institute

ANA Award for Excellence - Clinical and Scientific Excellence

Award Recipient: Thomas Wisniewski, MD, New York University Grossman School of Medicine

Derek Denny-Brown Young Neurological Scholar Award - Distinguished Teacher

Award Recipient Tracey Milligan, MD, MS, FANA, Westchester Medical Center, New York Medical College