Vestibular disorders are prevalent, particularly in aged people, and can cause significant impairment to quality of life including spatial disorientation. The sensory hair cells (HCs) in vestibular end organs sense head motions. Vestibular HCs degenerate as we age. Interestingly, vestibular end organs generate neural signals that terminate in the hippocampus. These connections contribute to the regulation of spatial memory and learning, although the mechanism is not completely understood. We are exploring whether loss of vestibular inputs to the hippocampus affects neurogenesis of granule cells in the dentate gyrus. A prior study showed a gradual increase in proliferative activity of granule cell progenitors after bilateral labyrinthectomy. We wondered if the same effect would occur when vestibular HCs are destroyed and if regeneration of HCs reverses the effect. We used a mouse that enables near complete killing of vestibular HCs upon injection of diphtheria toxin (DT). We administered the cell division tracer, BrdU, to experimental (HC-depleted) and control mice, all of which were adults, using 1) a pulse-fix paradigm to capture cells in the cell cycle or shortly thereafter and 2) a pulse-chase paradigm to study cells that differentiate into neurons. I am counting BrdU-labeled cells in the hippocampal dentate gyrus at different times after HC damage and in undamaged controls. In my poster, I will be presenting preliminary data that tests the hypothesis that we will see increased neurogenesis once HC inputs are lost. Once the study is completed, we hope to determine whether and how vestibular HC destruction and regeneration impact hippocampal neurogenesis. By exploring the relationship between the vestibular system and the hippocampus, we will build our understanding of how spatial orientation is regulated and whether vestibular regeneration can improve spatial orientation, which may inform on how to treat people with vestibular disorders in the future.

Challenges with social-emotional reciprocity, such as initiation of and response to social interactions, are a core diagnostic criteria of autism spectrum disorder (ASD), and many children with ASD experience challenges with expressive language. Prior research demonstrates parents are accurate reporters of language and fine motor skills development, but may under report social emotional reciprocity. The goal of my study is to discern how well parent concerns around child social-emotional reciprocity and language correspond to observed virtual interactions with their child. In a larger study investigating interventions for children with social communication concerns, parent participants of toddlers aged 25-41 months (n=41) completed the Toddler Autism Symptom Interview (TASI), a structured interview about core autism symptoms, over Zoom. Parent-child interactions were recorded in the same session while they completed the TELE-ASD-PEDS (TAP), a telehealth ASD assessment for toddlers. As part of the larger study, I am assisting with coding child expressive language, including use of words and multi-word combinations. For my independent research, I am coding child behavior on two tasks from the TAP, ‘calling the child’s name’ and ‘approaching others to play’. ‘Calling the child’s name’ is coded as the number of times the child stopped what they were doing to look at their caregiver when their name was called, while ‘approaching others to play’ is the number of times the child approached their caregiver during a 2-minute period where their caregiver was instructed to sit back and ignore their child. I will compare coded behaviors with corresponding items on the TASI. I hypothesize that parent reports will be more consistent with coded observations for language concerns than for social-emotional reciprocity behaviors. Understanding whether social-emotional reciprocity is being accurately reported by parents can help clinicians provide accurate diagnoses for ASD, especially given the critical role of parents in the diagnostic process.

Primary care providers are responsible for utilizing well-child-check-ups to screen toddlers for autism spectrum disorder and immediately refer children with increased likelihood to diagnostic and intervention services. Participating in intervention services at young ages is extremely impactful as it often allows children to develop their social, cognitive, and language skills. However, it is estimated that only 40% of children who screen at an increased likelihood for autism are being referred to recommended services by their providers. It is especially important to look at autism referral rates as autism is half as likely to receive a referral from a provider than other developmental concerns. This mixed-methods study used a video vignette and focus groups to investigate factors influencing primary care providers’ decision- making regarding autism referral in a well-child-check-up setting. We examine the role of provider attitudes, autism knowledge, and distribution of attention (information providers attend to during a visit). We anticipate that providers will exhibit low knowledge of autism and intervention, and believe information about autism that has empirically been proven to be false. Additionally, we expect that providers pay less attention to clinically significant behavioral information than physical information during a well-child-check-up. Overall, we aim to understand what influences provider’s referral decisions to provide insight on a development of a future primary care provider intervention that supports the increase of autism referral rates. Ultimately, improving the developmental prognosis of children with autism.

 COVID-19 is an infectious viral disease that is caused by the SARS-CoV-2 virus entering host cells through surface spike proteins that bind to surface ACE-2 receptors. Some anti-SARS-CoV-2 antibodies allow SARS-CoV-2 to also have antibody-mediated entry (AME) into immune cells, independent of the ACE-2 receptor. Instead, they often enter via Fcγ receptors. This phenomenon has been correlated with cytokine release syndrome, which occurs when the immune system has a highly inflammatory response to infection and is implicated in severe COVD-19 cases. It has also been shown that other antibodies have demonstrated inhibition of SARS-CoV-2 entry. During binding and viral fusion, all three receptor binding domains (RBD) of the spike protein fold to an upward conformation, which is necessary for binding. Inhibitory anti-SARS-CoV-2 antibodies can impede this process through competitive binding as well as mechanisms such as premature cleavage of the RBD or stabilizing a three-down conformation. We hypothesize that inhibitory antibodies can stop AME from occurring to varying degrees of effectiveness based on inhibitory mechanisms and avidity to the spike protein. To understand the dynamic between AME and inhibitory antibodies, we tested the infection levels of monocytes by SARS-CoV-2 pseudo-virus in the presence of antibodies shown to induce AME combined with varying concentrations of inhibitory anti-SARS-CoV-2 antibodies that have different mechanisms of affecting the spike RBD conformation. ELISA-based assays were also run to quantify antibody avidity to the spike protein. Analysis suggests that high concentrations of multiple neutralizing antibodies inhibit AME and that conformationally inhibiting antibodies are more effective at inhibiting AME than strongly activating ones. Studies of this type can aid in continued development of safe vaccines and therapeutics, as well as help understand how antibodies affect SARS-CoV-2 spike conformational regulation and therefore viral entry.