Adoptive T cell therapy is a promising therapeutic strategy for the treatment of many hematologic malignancies, however, its efficacy in solid tumors poses several challenges. Some of these challenges include the limited infiltration and activation of cytotoxic T cells due to the effects of a diverse immunosuppressive environment within the solid tumor. One of the main suppressive immune cells present in several solid tumors are regulatory T cells (Tregs) and high numbers of Tregs within the solid tumor have been correlated with poor prognosis. Therefore, there is a clinical need to develop strategies targeting the suppressive immune cells that limit the efficacy of adoptive T cell therapy. Tumors have highly dysregulated metabolism, which results in the secretion of multiple metabolites into the extracellular space. This allows a buildup within the tumor microenvironment, which may have an effect on the infiltrating immune cells. Our group has identified one metabolite, succinate, that enhances Treg numbers within the tumor microenvironment. Here we further explored the effect of succinate on the function of Tregs. To examine this, we identified tumor cell lines that produce succinate (lung and melanoma) and further altered these to modify the levels of succinate secreted by these cells. We then co-cultured high succinate secreting tumor lines with healthy donor CD4+ T cells that were isolated from PBMCs. We screened these cells and found that the higher levels of succinate resulted in higher numbers of Tregs and increased anti-inflammatory function, as evidenced by TGFb levels in Tregs. Future experiments will validate these findings in in vivo mouse models with the aim of developing synergistic approaches to enhance adoptive T cell therapy.

Around 7% of the population has developmental language disorder (DLD). DLD is a neurodevelopmental condition that affects learning, understanding, and using spoken language. It can be seen in early childhood but often goes undiagnosed into adulthood. Although DLD is diagnosed based on language differences, children with DLD also show motor differences. It is unknown whether adults with DLD still show motor differences as well. Motor control is the process of regulating the systems needed for voluntary movement and is what allows us to complete everyday tasks such as walking, writing, typing and anything else that includes movement. For this project, I have chosen to assess motor performance using a standardized assessment, the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2). Subtests will be used to test fine motor skills (e.g., precision, coordination) and gross motor skills (e.g., balance). For each subtest there are several activities to complete. Fine motor and gross motor are being tested as there is evidence that both are affected in children with DLD. In order to determine if the participants are in the DLD group or the TD group, we use an assessment involving following auditory directions and spelling unusual words. We will test 15 participants in each group. Participants will have learned English under the age of 2, be 18-45 years old, and have no history of speech, voice, hearing, or neurological diagnoses. I will analyze the data using unpaired t-tests on motor performance between the groups, as there are currently no norms for motor performance in this age range. I hypothesize that there will be motor control differences between the two groups, especially in areas such as balance, bilateral coordination, and manual dexterity. Learning more about DLD and motor control in adults will help with diagnosing and understanding how the disorder manifests in older populations.

Developmental language disorder (DLD) is one of the most common language disorders. It interferes with a person’s ability to learn and understand language. Previous studies have found that children with DLD struggle with motor skills more than their typically developing peers. There is also evidence that implicates the striatum (a subcortical brain structure) as a key difference in DLD; one study in in adolescents with DLD found reduced myelin in the striatum. Our study aims to examine how striatal myelination is associated with motor skill differences in adults with DLD. Participants between 18-45 years old will be tested on fine and gross motor skills using the Bruininks-Oseretsky Test of Motor Proficiency. Subtests of these skills include fine motor precision, fine motor integration, manual dexterity, upper limb coordination, bilateral coordination, and balance. In another session, the participants will undergo one hour of MRI scanning with a variety of functional and structural scans. I will analyze one type of MRI data to evaluate myelin markers in the striatum (MTsat and R1 maps). Individual composite scores for fine and motor skills will be correlated with the amount of myelin in the striatum to see if there is a significant relationship between myelin and motor skills in this population. We hypothesize that individuals with DLD will have lower motor skill scores than the control group, as well as a correlation between lower amounts of striatal myelin and motor skill deficiencies in the participants with DLD. We hope that the findings of this study will allow us to have a better understanding of which brain structures and behaviors are affected in adults with DLD. Research on DLD in adults is yet scarce, which consequently leads to limited resources and treatments for individuals with DLD.

Developmental Language Disorder (DLD) is a hidden neurodevelopmental impairment that impacts an individual’s ability to learn, comprehend, and use language to express their thoughts. While this is a common disorder (about seven times more prevalent than Autism Spectrum Disorder), there is limited research in adults with DLD. The primary goal of this project is to investigate articulatory variability during speech production in adults with DLD. Previous research shows that children with DLD have more articulatory variability during speech production compared to age-matched peers. On the other hand, other studies indicate comparable variability between groups. However, stimuli, kinematic measures, and inclusion criteria vary by study. Here, I will use state-of-the-art vocal tract magnetic resonance imaging (vtMRI) to capture the movements of the entire vocal tract, rather than focusing on just lip movements. Adults with and without DLD will produce sentences in the scanner. Sentences will be linguistically more and less complex. If I find increased articulatory variability in the DLD group during simple and complex sentences, I would interpret that as evidence of a general speech motor control difference. If I find increased articulatory variability only during more complex sentences, I would indicate that increased language load reduces speech motor control in this population. These data can help us build a better model of what might be happening in the brain in adults with DLD, ideally eventually leading to improved diagnoses and treatments for this common disorder.