The gut microbiome is a central regulator of overall health, and establishing mutually beneficial relationships between the host and resident gut bacteria is important for preventing the later development of pathologies such as ulcerative colitis, metabolic dysregulation, and colon cancer. While microbiota-reactive maternal IgA antibodies in the breastmilk have historically been considered to be a primary regulator of host-microbiota interactions, maternal IgG antibodies have historically been associated with the protection of neonates against pathogens. However, our lab has identified a novel function for microbiota-reactive maternal IgG2b and IgG3 antibodies in preventing dysregulated adaptive immune responses and reinforcing intestinal homeostasis in early life. To investigate how these maternal antibodies function, we created a mouse strain (IgG3^-/-) lacking IgG3 antibodies. Using IgG3^-/- dams, we were able to selectively prevent the transfer of maternal IgG3 antibodies to their pups while maintaining normal transfer of the other antibody isotypes. Compared to the pups born to wild type (i.e. antibody replete) dams, these pups displayed reduced weight gain, increased inflammatory gene expression, dysregulated T cell immunity, and increased susceptibility to intestinal colitis induced by dextran sodium sulfate (DSS). With our data suggesting an integral role for maternal IgG3 antibodies in limiting neonatal immune responses toward gut microbes, my current experiments aim to elucidate the underlying mechanisms by which these antibodies function. Using pups born to C1q deficient and FcγR deficient dams, which lack the ability to activate the complement pathway and FcγRs, respectively, I am aiming to test the roles of these antibody “sensing” pathways in maternal IgG3-mediated suppression of neonatal intestinal immunity. Defining these mechanisms not only gives us a clearer picture of the ways in which neonatal health is regulated; it also advances our ability to manipulate neonatal immunity and early life gut microbiome-targeted treatments to improve human health.

Breast milk is essential to the health and development of a child, containing antibodies that protect infants from common illnesses. However, exclusive breastfeeding is not always possible, and no infant formula substitutes for maternal antibodies. Previous studies on mice showed high germinal center (GC) B cell levels in response to the absence of maternal antibodies from breast milk early in life. Germinal centers B cells are involved in the adaptive immune system by secreting high affinity antibodies. However, little is known about the consequence of this, making characterizing the isotype, location, and duration of the antibody response in neonates (newborns) lacking maternal breast milk antibodies essential. For this project, I designed and optimized a tissue preparation and flow cytometry panel to assess memory B cells, GC B cells, and plasma cells (cells that secrete antibodies to fight infections and disease). The flow panel uses the cell markers CD138 and B220 to identify plasma cells by isolating the cells that are positive for CD138 and negative for B220. However, the marker CD138 can be sensitive to collagenase, resulting in the potential failure to identify plasma cells successfully. For this reason, I tested a range of collagenases, including Collagenase A, D, and IV. Concluding that CD138 was being cleaved off by all tested collagenases, I then used TACI as a new type of plasma cell differentiation marker. I evaluated these protocols by the viability of cells and the plasma cells' frequency. This protocol allows for the determination of localization, persistence, and isotype of early life B cells activated in the absence of breast milk.

We are currently investigating how neonates establish a symbiotic relationship between their developing immune system and the microbes colonizing their gut immediately post birth, and what role factors (e.g. antibodies) from the mother play in establishing this relationship. Lactobacillus is a genus of commensal bacteria that is commonly found in the neonatal intestine of both mice and humans. To track immune responses in the gut, I will create a fluorescent Lactobacillus species by transforming (genetically altering a cell through uptake and incorporation of outside DNA) a plasmid encoding a fluorescent protein into the bacterial cell. By engineering a fluorescent commensal species, we can track a normal, healthy immune-commensal interaction in vivo (in an animal model). Using this novel tool, we will study and compare how neonatal mice that do and do not receive antibodies from the mother post-birth differ in their immune response against these commensal species.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, restricted interests, and repetitive behaviors. Symptoms can vary widely in type and severity between individuals, but approximately 23% of children show clinical levels of aggression. Considering evidence for other racial disparities in healthcare, race/ethnicity is also a factor of interest in ASD research on disparities in diagnosis rates and severity. Previous studies have found ASD symptom severity, but not race, to be a significant predictor of physical aggression, though they investigated race alone and not as a moderator. This project aims to look at the relationship between measures of aggression and symptom severity, and the moderating effect of race/ethnicity on that relationship. 145 participants between the ages of 8-17 years with an autism diagnosis from an NIH-funded study were included in the analysis. Symptom severity was determined based on clinician observation of and interaction with the participant using the Autism Diagnostic Observation Schedule Calibrated Severity Score (ADOS CSS). Parents of the participants completed the Child Behavior Checklist (CBCL), rating their child’s level of emotional/behavioral problems. Questions were grouped together to yield scores in different “syndrome scale” categories, including aggressive behaviors. We will use multiple linear regressions to do predictive analysis on the relationships between symptom severity, aggression, and race. We expect that children with greater ASD symptom severity will display more aggressive behaviors. We also predict that there will be a moderating effect of race/ethnicity, with this relationship being stronger in white, non-Hispanic children than others. This study will provide insight into the diversity of ASD presentation, and it may help illuminate (biological or socially constructed) differences in ASD presentation between races/ethnicities and further efforts for equitable treatment.

Autism Spectrum Disorder is a neurodevelopmental disorder that is characterized by deficits in communication and social skills, and increased repetitive behaviors. These deficits also have the potential to impact executive functioning (EF). EF refers to the important mental processes of working memory, flexible thinking, and inhibitory control in order to reach a goal or complete a task. Language development centers around the ability to communicate, understand, and problem solve through verbal communication. Previous studies in typically developing (TD) children have found a moderately strong relationship between language ability and EF in children, as language allows for individuals to communicate more effectively, leading to higher EF ability when it comes to completing a task. The aim of this study is to analyze the correlation between language development and EF in individuals with and without ASD. As language and verbal communication requires recall and focus, it is likely that the two areas of EF most impacted by language development will be working memory and the ability to shift between tasks. Participants (ASD= 60, TD = 60) ages 8-17 years participated in a four-site study looking at sex differences in autism and completed the CELF-4, a clinician administered language measure. Parents of children completed the Behavior Rating Inventory of Executive Functioning Questionnaire (BRIEF), an 86 item EF questionnaire that results in a global executive composite score. We expect (1) that ASD youth will have greater impairments in language and EF compared to TD youth, (2) to see correlations between EF and language across both groups. Additionally, we predict higher EF and language scores for females than males. This study will provide a better understanding of language and EF that may be used to guide treatments, such as speech therapy for EF improvement.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, cognitive, and social impairments (Morgan et al., 2019). Earlier diagnosis has been shown to have a positive language trajectory for children with ASD. Delays in language development is one of the earliest signs of autism, and the more severe the child's early language delays are, the more likely they will have impaired language functioning (Mody & Belliveau, 2013). This project aims to evaluate if early language behavioral concerns raised by parents (age at first concerns of language) predict later language ability in youth with and without ASD. Participants included 68 children with ASD (males=34) between the ages of 8 and 17 years from the four site NIH funded study looking at sex differences in autism. All participants included met ASD criteria via standardized measures and had a verbal IQ >70. Parents of participants completed the Autism Diagnostic Interview (ADI-R), including questions related to when they observed the first signs of language and behavioral concerns and if concerns started at certain milestone ages (before 12 months, 18 months). Child participants completed a clinician-administered language task (CELF-IV), including answering questions related to recalling and formulating sentences. We predict that ASD children, whose parents identified concerns at an earlier age, have better language skills later in childhood. Previous research has indicated that females with ASD have a better language trajectory and have more vital verbal skills (Banks, 2020). Considering this research, we will explore sex differences, age of concerns, and later language development. This research can shed light on the importance of providing training to parents to recognize language delays early in children.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social, communicative, and behavioral impairments. Some individuals with ASD attempt to conceal their social impairments in a coping strategy known as camouflaging. Camouflaging includes (1) masking or suppressing instinctive autistic behaviors, and (2) compensating by memorizing and following social-communication norms. Even though camouflaging can help individuals with ASD secure jobs, avoid rejection, and form meaningful relationships, individuals with ASD qualitatively report that camouflaging is socially exhausting and can cause undue stress, anxiety, and feelings of inauthenticity. Given the qualitative reports of anxiety related to camouflaging, this study includes a quantitative investigation of the correlations between social camouflaging, mental health, and autistic traits across ASD and typically developing (TD) youth and young adults. Twenty ASD participants (Male=11) and 30 TD participants (Male=12) from the ACE GENDAAR network, a five site NIH funded project investigating gender differences in individuals with autism are included in the study. ASD diagnosis was confirmed via gold-standard diagnostic measures. Camouflaging was assessed using the Camouflaging Autistic Traits Questionnaire, a self-report measure of camouflaging behaviors. Mental health was assessed via the Adult Self Report or Youth Self Report, self-report behavioral checklists of co-morbid mental health symptoms. Social impairments associated with ASD were measured using the Social Responsiveness Scale, a parent-report questionnaire on their child's autistic traits. We hypothesize a positive correlation between the degree of camouflaging and the severity of depression/anxiety for both ASD and TD participants. We also predict camouflaging to be a better predictor of depression/anxiety severity than autistic traits. Data from this study can provide a better understanding of the prevalence of camouflaging in ASD and TD participants. It can also help create earlier mental health interventions for participants who camouflage their autistic traits.

Autism Spectrum Disorder (ASD) is a complex developmental disorder that is characterized by persistent challenges in social, behavioral, and communication functioning. The various challenges posed by ASD-related symptoms may result in lower quality of life (QoL) (Burgess & Gutstein, 2007). Previous research has focused on the relationship between others’ reports of autism traits (parent or clinician) and self- report of QoL for individuals with ASD (Mason et al., 2018), and only few reports have used self-report of autism traits and self-report of QoL. Self-report measures provide direct self-assessment rather than other’s interpreting a behavior from observation. The use of self-report provides a better understanding of how individuals with ASD evaluate autism traits and QoL without others’ bias. The present study aims to evaluate the relationship between self-reported autism traits and self-reported QoL in youth with and without ASD. Participants (ASD = 35, TD= 56) ages 16-34 year from a four-site NIH funded study on gender differences in autism were included. All participants met inclusionary criteria on standardized measures and had an IQ>70. Participants completed self-report assessment of autism traits (SAAT), a 58 item questionnaire on autism traits, and quality of life (Peds-QL) questionnaire, where questions about physical health, functioning, and emotional health were answered. We expect individuals with autism to report a lower QoL than TD peers replicating previous findings, and self-report of autism severity to be a predictor of QoL. We will additionally explore gender differences across these relationships to evaluate if females report lower autism traits considering more males are clinically diagnosed with ASD than females. These results will provide insight into the importance of timely recognition of QoL challenges in individuals with autism so supports can be developed and provided to young adults with autism.

Autism Spectrum Disorder (ASD) is a developmental disorder that is characterized by impairments in social, communication, and behavioral skills. One particular characteristic commonly seen in individuals with ASD is the presence of repetitive behaviors which include motor movements such as hand flapping or more ritualistic behaviors such as needing to touch objects in a particular order. Repetitive behaviors in ASD are similar to those seen in certain anxiety disorders, and the presence of a comorbid anxiety disorder in an individual with ASD has been shown to increase symptom severity, such as in social and communication impairments. Given the similarity between repetitive behaviors seen in ASD and anxiety disorders and the tendency for anxiety disorders to exacerbate ASD symptoms, this research aimed to assess the severity of repetitive behaviors between those with ASD and those with ASD + anxiety. Children between the ages of 8 and 17 participated in an NIH funded study (ASD only = 145) (ASD + anxiety = 67). Parents completed the ACE Medical History interview about their child and completed the Repetitive Behavior Scale - Revised (RBS-R) which is a 44-item questionnaire that assesses repetitive behaviors on 6 different subscales. We predict that the ASD + anxiety group will have a higher severity score (total and subscales) when compared to the ASD only group. Additionally, we will explore sex differences across these relationships. Overall, the information gained in this study will shed further light on symptom severity in subsets of the ASD population, thus better informing the development of treatment for individuals.