The New Jersey Governor's Council for Medical Research and Treatment of Autsim is happy to introduce the gratees for our Concept Project and Felloswship Porgram awards. For more information on the Council's programs and current opportunities, please see our Current Grant Initiatives.
| Name | Institution | Project Title |
| Anat Kreimer, Ph.D. | Rutgers University | Decoding Autism Regulatory Variants Using Computational Genomics in Human iPSC-Derived Neurons. |
| Description: Researchers can read protein coding DNA sequence and predict the amino acid sequence of proteins. However only about 2% of the human genome encodes protein, with most of the genome being non-coding. Noncoding DNA regulates gene expression but until recently it was impossible to “gaze” at non-coding DNA and identify functional sequences. Importantly, thousands of autism mutations map to non-coding sequence, but it remains unknown which of these non-coding variants are functional. This is a very significant gap in our understanding of autism etiology. The goal of this proposal is to identify functional non-coding ASD mutations by leveraging stem cell derived human neurons in combination with new multi-omic and computational approaches. | ||
| James Millonig, Ph.D. | Rutgers University | A p53 Mediated Mechanism for 16p11.2 ASD Hyperproliferation Phenotype. |
| Description: Altered proliferation is an important convergence point for autism risk (5,16,17), but the contributing signaling pathways have yet to be identified. This information is needed to develop new ASD treatments. To define these pathways, the Millonig lab has been studying a small deletion on human chromosome 16 called 16p11.2 (16pDel). The mutation deletes only 28 genes and is one the largest contributors to autism risk (8). 16pDel individuals often have diagnoses suggestive of proliferation defects, including neuroblastoma, a neuronal cancer, and macrocephaly, enlarged head (8,9). We have utilized human stem cells to derive neural progenitor cells (NPCs) and have discovered a reproducible and robust hyperproliferation phenotype in 16pDel individuals with autism. | ||
| Name | Institution | Project Title |
| Vanessa Bal, Ph.D. | Rutgers University | Boosting Engagement and Skill Acquisition through Technology and Personalization: A Pilot Trial of Enhanced Transdiagnostic Behavioral Therapy. |
| Description: Autistic individuals are at high risk for co-occurring conditions, such as depression and anxiety. Yet, there is very little research on treatments to address these difficulties autistic adults. The long-term goal of this project is to expand the availability of programs to promote the mental health and quality of life for autistic adults. To do this, this project focuses on developing ways to improve Group Behavioral Activation Treatment (GBAT) for use with autistic adults. This study will be used to inform final changes to GBAT+ and be used to make decisions regarding the design of future GBAT+ studies to establish if GBAT+ is an effective way to support autistic adults. This project has both immediate and long-term public health impact by providing direct support of autistic adults and contributing to training of psychologists at Rutgers who will go on to support the mental health needs of autistic adults in the community. | ||
| Yu-Lun Chen, Ph.D. | Kessler Foundation | Racial, Ethnic, and Language Disparities in Autism Health Service Use among Children in NJ: Assessing Longitudinal Trends of Service Gaps and the Role of Social Determinants. |
| Description:Children with autism require early and ongoing access to multiple medical and therapy services for healthy development and socialization. These health services include primary and specialized medical services (e.g., developmental-behavioral pediatrics and psychiatry) as well as specialized therapy services (e.g., occupational therapy, physical therapy, psychology, and speech therapy). However, research shows that Black and Hispanic/Latino children, as well as children from families with limited English proficiency, have less access to these health services and report more unmet service needs. Given that 45% of New Jersey residents are racial or ethnic minorities and 31% speak a primary language other than English, there may be a large proportion of children with autism in New Jersey who are not receiving the care they need. To understand this critical issue, this study proposes to investigate trends in the use of health services over time among children with autism living in New Jersey. And, it will investigate whether service gaps by race/ethnicity, language preference persist over time and differ by the characteristics of the places where people live. | ||
| Name | Institution | Project Title |
| Adele Goldberg, Ph.D. | Princeton University | Innovative intervention for Vocabulary Learning. |
| Description:Perhaps the most common and frustrating challenge for autistic individuals and their families stems from delays in language and communication skills, resulting in cascading negative effects on social and educational development. The proposed project is based on a new perspective on language learning in autism that builds on the recognized tendency for autistic people to focus on specifics to the neglect of generalizations. The research team will create and rigorously test an innovative and potentially powerful technology-based intervention to jump-start word-learning in children on the spectrum. | ||
| Katherine Gotham, Ph.D. | Rowan University | Leveraging Eyetracking Technology to Index Depressed Mood in Minimally Verbal Autistic Adults. |
| Description: Depression is one of the most common and impairing clinical problems among the autistic adult community: People with autism are about 4 times more likely to experience a depressive episode compared to people without autism. Though depression appears to be most common among autistic individuals who use spoken language fluently, it is possible that similarly high rates of depression go undetected in autistic adults with limited spoken language, because these adults are less likely or less able to provide verbal accounts of their symptoms. This study proposes to test a simple eyetracking task as a way to measure depressed mood in autistic adults with limited spoken language. The purpose of the study is to see if these pupil changes can be used to capture difference between levels of depressive symptoms in autistic adults with limited spoken language, as they did in a previous study of verbally fluent adults. The research team predicts that minimally verbal autistic adults who show a larger and longer pupil response to pictures of sad faces will also have higher levels of depressive symptoms, as rated by their parent or caregiver. This study may also help health professionals to identify people in these communities who need special care to support their mental health. | ||
| Name | Institution | Project Title |
| Jack DeLucia | Rutgers University | Neuropilin 2 Regulates Distinct Cellular Processes in Different Basal Ganglia Neuron Populations Necessary for Complex Behaviors in Mice. |
| Description: Consistent with the prevailing hypothesis of imbalance in excitatory/inhibitory synaptic connections in specific brain regions, abnormalities in the neuronal morphologies, connections and functions of the striatum, a structure in the basal ganglia, are associated with the development of ASD. Previously, work from our group and others have demonstrated that the cell surface receptor, Neuropilin-2 (Nrp2), which binds the family of semaphorin guidance molecules, is a key player in regulating the development of excitatory and inhibitory neuronal connections, and polymorphism mutations identified in this gene locus are associated with higher incidences in individuals diagnosed with ASD. This study will focus on the role of Nrp2 in the development of both inhibitory primary (medium spiny neurons) and interneurons in the mouse striatum as it pertains to ASD-like behaviors. Using sophisticated mouse genetics, cellular and behavioral approaches, we will investigate changes in the excitatory/inhibitory balance of the striatal circuitry and will assess how the loss of Nrp2 in specific striatal neuronal populations affects autism-relevant behaviors. Our anticipated results from this study will provide a better understanding of the molecular mechanisms involved in regulating inhibitory neuron development, synapse organization and behavioral output pertaining to ASD. | ||
| Courtney R. McDermott | Rutgers University | Early Life Microbiota Dysbiosis and Autism: Effects on Neurodevelopment and Behavioral Outcomes. |
| Description: Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is typically detected in childhood and persists throughout life. Although the causes of ASD are unknown, extensive research suggests the combination of genetic vulnerability and environmental factors likely contribute to ASD. This proposal aims to provide an in-depth exploration of how cephalosporin antibiotics, environmental factors associated with increased ASD risk, cause microbiome dysbiosis and co-occurring brain alterations in the 16p11.2 microdeletion mouse model. We will examine the effects of early life antibiotic exposure on developmental neurogenesis, neural gene expression, behavior, and microbial community composition. What we discover will have significance to the autism community, given the common use of antibiotics in childhood and strong association of the 16p11.2 microdeletion with ASD. | ||
| Iva Salamon | Rutgers University | The Role of the Autism Risk Gene Celf4 in the Specification of the First Synapses During Early Neocortical Development. |
| Description: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with underlying synaptic dysfunction; human genetic and imaging studies have linked the developing cortex and impaired prenatal connectivity with ASD. The earliest born neurons that form different types of synapses are located in the evolutionarily conserved transient fetal zone, called the subplate which shows prolonged prenatal development in both rodents and humans and mysteriously disappears at early postnatal stages; a fact which makes this region historically difficult to study. mRNA translation (protein synthesis), regulated by RNA binding proteins (RBPs) at the post-transcriptional level, might be one potential mechanism which could explain how these early synapses are formed during the earliest stages of brain development and what their connection is to ASD-related changes. One important RBP, which is also an ASD high confidence gene, is CUGBP Elav-Like Family Member 4 (Celf4); our preliminary data show that Celf4 is found in the SP and that it regulates mRNAs and synapse development. We hypothesize that Celf4 regulates the balance of synaptic subtypes in SP via mRNA translation regulation. | ||
| Fernando Velloso, Ph.D. | Rutgers University | Perinatal Interleukin-6 Induced Neuroinflammation and SVZ Progenitor Cell Dysgenesis. |
| Description: The incidence of Autism Spectrum Disorders (ASD) has been steadily increasing for decades and New Jersey has almost double the national rate. Epidemiological and animal studies have established a strong association between infections and other environmental factors that cause inflammation during pregnancy with an increased risk for ASD in the offspring. A central pro-inflammatory cytokine, interleukin-6 (IL-6), is increased both in animal models and in the blood of children with ASD. Our preliminary data show that transiently increasing systemic IL-6 in newborn mice induces acute neuroinflammation, changes the proliferation of specific subsets of progenitors within the subventricular zone and promotes enduring anti-social and repetitive behaviors. The goals of my fellowship are to establish how transiently increasing IL-6 affects the migration of immune cells into the brain to create a neuroinflammatory state and to investigate the signature transcriptomic changes that occur within the progenitors of the subventricular zone induced by IL- 6 that, in turn, affect how the neurons and glial cells of the brain develop. | ||
| Name | Institution | Project Title |
| Alessandro Bortolami | Rutgers University | A Novel Murine Model to Study Potassium Channel-Related Autism Spectrum Disorder. |
| Description: Autism spectrum disorder (ASD) is a neurological condition characterized by learning impairment, motor deficits, and restricted repetitive behaviors. ASD can be caused by defects in the brain probably arising as early as gestation. We have found that a protein named KCNB1 causes malformations in the cortex and behavioral defects in mice that resemble typical behaviors of ASD children. Our project aims at studying how KCNB1 protein causes brain malformations and corresponding behavioral deficits. We hypothesize that by studying these mice we can better understand what causes ASD in humans. | ||
| Erin McKenney | Rowan University | Examining Depression, Anxiety, and Trauma in First-Semester Autistic College Students. |
| Description: Depression and anxiety are more common in autistic adults than in the general population, and these mental health concerns have been named by autistic adults as a high priority for future research. Many individuals have identified the transition to college as an especially difficult time point due to changes in routine, social support, and demands. Despite these concerns, there has been very little research exploring what predicts greater mental health problems over time in this population. The current study explores how negative repetitive thinking, social satisfaction, and traumatic sexual experiences predict and maintain depression and anxiety symptoms during the college transition. Additionally, this study explores how common these potential predictors of depression and anxiety are in autistic college students compared to non-autistic peers. It is expected that higher negative repetitive thinking, lower social satisfaction, and experiencing sexual trauma will be related to increased depression and anxiety symptoms, and that both these predictors and the depression and anxiety symptoms will be more common in autistic participants than in non-autistic participants. This work will help to build better prevention and intervention strategies for depression and anxiety in the underserved population of autistic adults, particularly in the college setting. | ||
| Denise Robles | Rutgers University | Modeling Long-Range Connectivity Deficits in ASD using Cerebral Organoids. |
| Description: Autism spectrum disorders (ASD) are highly prevalent, particularly in New Jersey where an estimated one in 35 children are affected. As a spectrum disorder, ASD may severely impact patients’ quality of life and pose a significant socioeconomic burden. Both genetic and environmental factors have been tied to causing ASD. While recent years of research have seen great strides in uncovering specific genetic and behavioral phenotypes at the cellular, molecular, and network circuitry levels, there remains a lack of understanding regarding human- specific pathophysiology. This work focuses on developing a system to recapitulate ASD-relevant pathophysiology using three-dimensional (3D) cerebral organoids (COs) derived from patient-specific human induced pluripotent stem cells (hiPSCs) carrying a genetic mutation in the SETD1A gene known to cause syndromic autism. This novel experimental paradigm combines human stem cell technology and microfabrication bioengineering to recapitulate the long-range projections formed between brain regions during human neurodevelopment. The central hypothesis is that this platform will promote the formation of long-range connections between CO cultures and demonstrate impaired maturation and functional activity in ASD COs. Successful implementation of this proposed work will: 1) allow the elucidation of molecular and cellular mechanisms underlying the long-range connectivity deficits in ASD and the contribution of genetic risk factors; and 2) provide an innovative platform that can be used for drug screening for devising novel therapeutics and treatment regimens through selection of pharmacological interventions, dosing, and frequency of administration. | ||
| Sofia Gonzalez Salinas, Ph.D. | Rutgers University | Cortical Circuits Regulating Social Behaviors. |
| Description: Impaired social interactions are a core symptom in patients with Autism Spectrum Disorders (ASD). Deficient social skills can deeply impact ASD patient’s daily activities including employment, forming affective bonds and could be linked to anxiety and depressive symptoms. While several regions of the brain may be involved in social deficits in ASD patients, the activity of cells in the medial prefrontal cortex (mPFC) may be a critical mechanism to promote healthy interactions. Work in animal models of ASD suggests that social deficits may be caused by altered activity of cells located in the mPFC that are connected with other brain areas. However, the neuronal circuits of the mPFC controlling social behaviors are not well understood. We will study in mice a subpopulation of cells of the mPFC that by projecting to the hypothalamus or amygdala may modulate social interactions. Using state-of-the-art techniques that provide high cellular resolution and time regulation of neuronal activity we will control and record the activity of these two mPFC circuits during social interactions. We hypothesize that increased activity in one circuit and the repression of the other will promote social interactions. Our proposal will provide critical knowledge to understanding the functional basis of social behaviors that might be applied to develop non-invasive strategies that improve social skills in ASD patients. | ||
