About

The Hart Lab uses genetic and molecular approaches in the small nematode C. elegans to understand the conserved mechanisms underlying neurodegenerative disease and nervous system function. We focus on delineating cellular and molecular pathways pertinent to Huntington's disease, Spinal Muscular Atrophy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alternating Hemiplegia of Childhood, and other neurodegenerative diseases. We also study the genetic and molecular mechanisms regulating sleep and fatigue.

Research topics

• Computer Science
• Cell biology
• Biology
• Neuroscience
• Genetics
• Pathology
• Medicine
• Library science

Selected publications

• Divergent inflammatory and neurology-related protein levels in long COVID following primary and breakthrough SARS-CoV-2 infections

  Communications Medicine · 2026-04-13

  articleOpen access

  Long COVID is a complex condition where symptoms persist for more than 3 months after SARS-CoV-2 infection and affects an estimated 5-30% of individuals. While persistent inflammation has emerged as an important feature of this condition, it is unclear if immune responses from COVID-19 vaccination or SARS-CoV-2 re-infection exacerbate or mirror the initial inflammatory responses. We quantified 182 inflammatory and neurology-related proteins in plasma using multiplexed affinity proteomics. Plasma samples from the COVID PROFILE cohort conducted in Victoria, Australia, were collected 6-9 months after first infection, but before COVID-19 vaccination from individuals who had recovered from COVID-19 (n = 21) or from individuals with long COVID (n = 12). To establish baseline plasma profiles, protein levels were benchmarked against unvaccinated, SARS-CoV-2 naive individuals (n = 24). In addition, we performed longitudinal analysis in a subset of individuals (n = 34), where paired samples collected 2-4 weeks after a third COVID-19 vaccine dose and after SARS-CoV-2 breakthrough infection were available to assess inflammatory and neurology protein plasma levels after antigen exposure in these contexts. In this cohort Boruta feature selection and lasso regression models identified IL-20, HAGH, NAAA, CLEC10A, LXN, and MCP-1, TRAIL, G-CSF, NBL1, and CCL23 as best discriminating proteins when comparing the long COVID group to groups of either healthy or COVID-19 recovered. Notably, longitudinal analysis indicated differences in the levels of a subset of plasma proteins following primary infection compared to after COVID-19 booster vaccination and breakthrough infection within the groups. These findings suggest that there is an altered immune response outcome primarily observed in individuals with long COVID upon re-exposure. Bansal, Olechnowicz et al. examine levels of inflammatory and neurology-related proteins in individuals with long COVID. They find that vaccination and breakthrough infections are linked to differential plasma levels of a subset of proteins compared to initial infection suggesting an altered immune response outcome upon re-exposure. Long COVID is a condition in which people continue to have symptoms for more than three months after SARS-CoV-2 infection. Ongoing inflammation is thought to contribute to long COVID, but it is unclear whether COVID-19 vaccination or re-infection with SARS-CoV-2 lead to similar, worse or different inflammatory responses compared with the initial infection in people with this condition. We examined blood proteins linked to inflammation and the nervous system to better understand these responses in people with long COVID, individuals that had completely recovered from the first infection and healthy controls. We found that in both long COVID individuals and completely recovered people there were different changes in the level of some immune-related proteins after vaccination or re-infection compared with the response after the original infection suggesting a different immune response from the initial infection upon re-exposure.

  PublisherDOI

• <i>C. elegans</i> models of alternating hemiplegia of childhood have dominant neuromuscular junction defects

  Disease Models & Mechanisms · 2026-05-01

  articleOpen accessSenior author

  Dominant missense mutations in ATP1A3, encoding a Na+, K+ ATPase α-3 subunit, can cause Alternating Hemiplegia of Childhood (AHC), but how these mutations lead to AHC remains unclear. Here, we establish the first C. elegans AHC models by introducing AHC-causing ATP1A3 patient mutations (D801N, E815K, L839P, and G947R) into the orthologous gene, eat-6, using CRISPR/Cas9. Homozygous C. elegans AHC model animals have recessive developmental defects. Heterozygous AHC model animals have dominant defects in neuromuscular junction (NMJ) function that are inconsistent with haploinsufficiency and dominant sleep or arousal defects. Previous work in a Drosophila G755S AHC model found that loss of a K⁺-dependent, Na⁺/Ca²⁺ exchanger exacerbated neuronal defects. We introduced a loss-of-function allele of the orthologous C. elegans gene, ncx-4, into C. elegans AHC models; loss of ncx-4 function did not consistently alter C. elegans AHC model defects across alleles. Our results establish novel C. elegans models of AHC with robust phenotypes, demonstrate that AHC mutations disrupt NMJ function, and provide proof-of-concept for discovering cross-species modifiers of AHC-related phenotypes.

  PublisherDOI

• <i>C. elegans</i> models of Alternating Hemiplegia of Childhood have dominant neuromuscular junction defects

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-26

  articleOpen accessSenior authorCorresponding

  Abstract Dominant missense mutations in ATP1A3, encoding a Na + , K + ATPase α-3 subunit, can cause Alternating Hemiplegia of Childhood (AHC), but how these mutations lead to AHC remains unclear. Here, we establish the first C. elegans AHC models by introducing AHC-causing ATP1A3 patient mutations (D801N, E815K, L839P, and G947R) into the orthologous gene, eat-6, using CRISPR/Cas9. Homozygous C. elegans AHC model animals have recessive developmental defects. Heterozygous AHC model animals have dominant defects in neuromuscular junction (NMJ) function that are inconsistent with haploinsufficiency and dominant sleep or arousal defects. Previous work in a Drosophila G755S AHC model found that loss of a K⁺-dependent, Na⁺/Ca²⁺ exchanger exacerbated neuronal defects. We introduced a loss-of-function allele of the orthologous C. elegans gene, ncx-4 , into C. elegans AHC models; loss of ncx-4 function did not consistently alter C. elegans AHC model defects across alleles. Our results establish novel C. elegans models of AHC with robust phenotypes, demonstrate that AHC mutations disrupt NMJ function, and provide proof-of-concept for discovering cross-species modifiers of AHC-related phenotypes. Summary Statement We report the first C. elegans models of Alternating Hemiplegia of Childhood. D801N, E815K, L839P, and G947R AHC model animals have recessive development defects and dominant neuromuscular defects.

  PublisherDOI

• Associations of Marijuana Use History with Progression from Living Donor Candidate Evaluation to Approval: Analysis of the US SRTR Living Donor Collective

  American Journal of Transplantation · 2025-08-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Work in Progress: Exploring the Landscape of Stressors Experienced by Doctoral Engineering Students

  2024-02-07 · 4 citations

  articleSenior author

  Abstract Graduate education faces serious issues of high attrition rates and prevalent mental health distress rates. Prior research has linked both attrition and mental health distress to the effects of high stress environments in graduate student workplaces (e.g., Stubb et al., 2014, Bekkouche et al., 2022). Research on doctoral student stress often focuses on single stressors, where generally only one source of stress is the focus of a study. While deep explorations of stressors are important, little work has been done to observe and compare stressors across the broad range of sources experienced by doctoral students and none of that work has looked at changes in stress over time. Thus, we interviewed 55 doctoral engineering students four times each about their experiences with stress during the 2021-2022 academic year. We conducted a thematic analysis of interviews grounded in the job-control-hindrance support model (Karasek, 1979; Dawson et al., 2015) and using qualitative codes emerging from the data. Coding for the broad landscape of stressors resulted in identifying major themes consistent with prior literature (e.g., advisor-related, coursework-related stressors) and sub-stressors within those themes (e.g., writing feedback from advisors, balancing coursework with other expectations). Sub-stressors within themes were largely consistent with the literature with some novel sub-stressors or stressors which were differently prevalent compared with reports from prior literature. Particularly salient within our data are advisor interactions and expectations, research direction and workload, and issues related to work-life balance. We report the top ten sub-stressors that are present in our data corpus based on frequency of coded responses. We also report on trends in students' coping strategies and situate these within prior literature on coping landscapes (e.g., Sallai et al., 2022). Finally, we suggest implications for further research and implications for doctoral advisors and students. References Bekkouche, N. S., Schmid, R. F. & Carliner, S. (2022). "Simmering Pressure": How systemic stress impacts graduate student mental health. Performance Improvement Quarterly, 34, 547-572. Dawson, K. M., O'Brien, K. E., & Beehr, T. A. (2016). The role of hindrance stressors in the job demand–control–support model of occupational stress: A proposed theory revision. Journal of Organizational Behavior, 37, 397– 415. Karasek, R. A. (1979). Job demands, job decision latitude, and mental strain: Implications for job redesign, Administrative Science Quarterly, 24(2), 285-308. Sallai, G. Vicente, J., Shanachilubwa, K., Berdanier, C. (2022, August). Coping landscapes: How graduate engineering students' coping mechanisms correspond with dominant stressors in graduate school, Paper presented at 2022 ASEE Annual Conference & Exposition, Minneapolis, MN. Stubb, J., Pyhältö, K., & Lonka, K. (2014). Conceptions of research: The doctoral student experience in three domains, Studies in Higher Education, 39(2), 251-264.

  PublisherDOI

• A conserved role for ALG10/ALG10B and the <i>N</i> -glycosylation pathway in the sleep-epilepsy axis

  medRxiv · 2024-12-13 · 4 citations

  preprintOpen access

  ABSTRACT Congenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described for ALG10 , encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP associations with short sleep duration, reduced napping frequency, later sleep timing and evening diurnal preference as well as cardiac traits at a genomic locus containing a pair of paralogous enzymes ALG10 and ALG10B . Modeling Alg10 loss in Drosophila, we identify an essential role for the N -glycosylation pathway in maintaining appropriate neuronal firing activity, healthy sleep, preventing seizures, and cardiovascular homeostasis. We further confirm the broader relevance of neurological findings associated with Alg10 from humans and flies using zebrafish and nematodes and demonstrate conserved biochemical roles for N -glycosylation in Arabidopsis . We report a human subject homozygous for variants in both ALG10 and ALG10B arising from a consanguineous marriage, with epilepsy, brain atrophy, and sleep abnormalities as predicted by the fly phenotype. Quantitative glycoproteomic analysis in our Drosophila model identifies potential key molecular targets for neurological symptoms of CDGs.

  PublisherOA PDFDOI

• Cohort Profile: A longitudinal Victorian COVID-19 cohort (COVID PROFILE)

  medRxiv · 2023-04-29 · 6 citations

  preprintOpen access

  Abstract Purpose The COVID PROFILE cohort is a longitudinal clinical study based in Victoria Australia, which was established to understand immunity to SARS-CoV-2 in a low transmission population setting and to identify immunological markers of long-term immunity and immune-dysregulation after both infection and vaccination. Additionally, this cohort was established as a biobank resource for researchers to address other health-related immunological questions. Participants We enrolled 178 adult community members, including household contacts, who had either recovered from a SARS-CoV-2 infection or were SARS-CoV-2 naïve. Only participants ≥18 years of age and, in the case of female participants, non-pregnant women at the time of enrollment were included in the study. Detailed COVID-19 clinical data, vaccination status, medical history and demographics was collected. Findings to date At enrollment, we found that 87.8% of COVID-19 recovered individuals were seropositive with detectable levels of anti-SARS-CoV-2 IgG antibodies. Seronegative COVID-19 recovered individuals included asymptomatic individuals or participants that were enrolled more than 12 months after their COVID-19 diagnosis. Except for one individual who was seropositive at baseline despite a previous SARS-CoV-2 PCR negative diagnosis, all household contacts and other community members enrolled as SARS-CoV-2 PCR negative, were seronegative for all SARS-CoV-2-specific antibodies tested. The infection rate (re-infection or new infection) during 24 months of the study was 42.7%, as determined by either rapid antigen tests, PCRs or serology screens. Of the SARS-CoV-2 recovered participants, 32.6% reported ongoing symptoms at enrollment of which 47% had already experienced ongoing symptoms for more than 12 weeks. Future Plans COVID PROFILE will be used to comprehensively understand temporal immunity to SARS-CoV-2 and COVID-19 vaccines and to understand the impact of host immunological composition on such immunity and symptom severity. Additionally, studies focusing on understanding immunity following breakthrough infections and immunological risk factors that contribute towards development of long COVID are planned. Limitations/Strengths of the study Extensive clinical information is available and longitudinal samples (blood, saliva and oropharyngeal swabs) collected at regular intervals up to 2.5 years after initial enrolment. This low SARS-CoV-2 transmission population cohort, enables exploration of difference in both the acquisition and maintenance of naturally acquired and vaccine-induced immunity not confounded by prior, frequent and/or undetected exposures. Extensive biobank of numerous blood fractions and biospecimen enables further exploration of mucosal immunity, nasal microbiome and humoral and cellular immunity over time. The cohort may be limited in addressing research questions regarding outcomes and risk factors and their associations where low incidence is expected.

  PublisherOA PDFDOI

• The time is ripe to reverse engineer an entire nervous system: simulating behavior from neural interactions

  arXiv (Cornell University) · 2023-08-12 · 2 citations

  preprintOpen access

  Just like electrical engineers understand how microprocessors execute programs in terms of how transistor currents are affected by their inputs, neuroscientists want to understand behavior production in terms of how neuronal outputs are affected by their inputs and internal states. This dependency of neuronal outputs on inputs can be described by a state-dependent input-output (IO)-function. However, to reliably identify these IO-functions, we need to perturb each input and combinations of inputs while observing all the outputs. Here, we argue that such completeness is possible in C. elegans; a complete description that goes all the way from the activity of every neuron to predict behavior. The established and growing toolkit of optophysiology can non-invasively capture and control every neuron's activity and scale to countless experiments. The information from many such experiments can be pooled while capturing the inter-individual variability because neuronal identity and function are largely conserved across individuals. Just like electrical engineers use transistor IO-functions to simulate program execution, we argue that neuronal IO-functions could be used to simulate the impressive breadth of brain states and behaviors of C. elegans.

  PublisherOA PDFDOI

• Starting a C. elegans Research Laboratory: Practical Advice

  Methods in molecular biology · 2022-01-01

  article1st author
  PublisherDOI

• C. elegans

  Methods in molecular biology · 2022-01-01 · 2 citations

  bookSenior author
  PublisherDOI

Recent grants

• NIH Grant R01NS055813

  NIH · $1.6M · 2015

• NIH Grant R55GM057918

  NIH · $100k · 1999

• NIH Grant R01GM057918

  NIH · $2.0M · 2005

• NIH Grant P01NS066888

  NIH · $13.2M · 2016

• NIH Grant R01GM078171

  NIH · $1.2M · 2013

Frequent coauthors

• Saba N. Baskoylu

  Massachusetts Institute of Technology

  62 shared

• Jeremy Lins

  Brown University

  45 shared

• Kelsey N. Schuch

  Allen Institute for Brain Science

  43 shared

• Maria Dimitriadi

  University of Hertfordshire

  42 shared

• Cindy Voisine

  Northeastern Illinois University

  36 shared

• Huiyan Huang

  Guangdong General Hospital

  33 shared

• Natalie Chapkis

  Brown University

  31 shared

• Jonah Simon

  Providence College

  31 shared