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Current Grantees

Current Grantees

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.

FY2023 Basic Research Pilot Projects

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.

FY2024 Basic Research Pilot Projects

Name	Institution	Project Title
Peng Jiang, Ph.D.	Rutgers University	Regulation of Human Forebrain Development by ASD-Associated Cytokines in Human iPSC-derived Cerebral Organoids
Description: Extensive clinical studies have demonstrated that maternal infections, allergies, autoimmune diseases, obesity or pollution during pregnancy increase offspring risk for developing ASD by 2-4 fold. How these conditions enhance the frequency of ASD remains largely unknown. But, one signal that is produced by the maternal immune system that is consistently increased and that can cross the placenta and then cross into the fetal brain is the cytokine interleukin-6 (IL-6). Importantly, published studies using animal models have shown that IL-6 is both necessary and sufficient to cause several behavioral phenotypes associated with ASD. However, prior studies have almost exclusively used murine models, which present challenges to translate those results to human biology considering that human neural progenitors are more complex than those in mice. Therefore, we propose to establish mini-brain cultures comprised of human neural progenitors (from human induced pluripotential stem cells) and then determine how IL-6 exposure alters their production of excitatory vs. inhibitory neurons as well as their capacity to produce non-neuronal cells. These human mini-brains will contain those human NPCs that are present during the end of the 2nd trimester of development, which is when exposure to stimuli that cause maternal inflammation are most likely to increase the probability of a child developing autism. The central premise of this application is that IL-6 alters human NPC gene expression, which skews their specification to glutamatergic excitatory neurons, from inhibitory neurons, and compromises macroglial cell differentiation (i.e. astrocytes and oligodendrocytes). Presently no treatments are available to prevent or to reduce the incidence or severity of ASD; however, drugs targeting the IL-6 pathway are used to treat rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Castleman disease, SARS-Cov2 and others. Clinical and preclinical studies continue to implicate prenatal IL-6 exposure in the etiology of ASD, providing rationale for re-purposing these IL-6 pathway inhibitors for their therapeutic potential. Such treatments could save billions of dollars annually and relieve the suffering of millions of individuals worldwide.

Chiara Manzini, Ph.D.	Rutgers University	Unraveling the diversity of PDE4D signaling to understand the mechanisms of action of PDE4D inhibitors.
Description: To date, the treatment options for the main symptoms of autism affecting social interactions and leading to repetitive behaviors mostly rely on behavioral therapy with a psychologist. No drugs can be prescribed to improve social function or learning deficits. Only recently, a clinical trial in individuals with Fragile X Syndrome, the most common genetic cause of autism, has pointed to drugs that block the enzyme phosphodiesterase 4D (PDE4D) as a possible treatment. PDE4D controls how brain cells (neurons) respond to outside signals from other neurons, hormones, and growth factors. However, PDE4D also functions in other cells throughout the body and its specific site of action in neurons is poorly understood. The first goal of our proposal is to define how PDE4D functions at the sites that control communication among neurons, the synapses. Then we will explore its role in the brain region that controls memory, the hippocampus, also studying mice where the Fragile X Syndrome gene has been removed to understand where PDE4D inhibitors are acting. Overall, the proposed research will not only better explain how PDE4D inhibitors function, but also possibly lead to the development of more specific drugs.

FY2025 Basic Research Pilot Projects

Name	Institution	Project Title
Xin Di, Ph.D.	New Jersey Institute of Technology	Exploring Eye Movement Patterns and Brain Activity in Autism Spectrum Disorder Through Deep Learning-Based Eye-tracking with Functional MRI.
Description: This study is about understanding eye movements in children and young adults with autism. Individuals with autism often show different patterns of looking at others during social interactions, such as avoiding eye contact. But it's hard to track eye movements using special cameras in a brain scanner. But a new technology called deep learning has made it possible to study eye movements using brain scans alone. This is exciting because it means we can study eye movements in larger groups of people who have already had functional MRI scans. In this study, we will improve the deep learning model to make it even better at tracking eye movements. We will also study where the participants look when they watch a video or just lay still. Our goal is to see if there are differences in how people with autism and those who develop typically look at things. This study will give us new information about how people with autism see the world. The results could help us understand autism better and improve how we diagnose it in the future.

FY2023 Clinical Research Pilot Projects

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.

FY2024 Clinical Research Pilot Projects

Name	Institution	Project Title
Christina Simmons, Ph.D.	Rowan University	Randomized Pilot Evaluation of Healthcare Professional Training Using a Virtual Reality Training Program for Severe Behavior in Children with Autism.
Description: In this project, we will develop and evaluate a virtual reality (VR) healthcare professional training tool that maximizes the effect of critically needed behavioral training for clinicians working with children with autism spectrum disorder who engage in severe unsafe and interfering behavior. The VR training tool addresses access barriers to training by allowing clinicians to practice intervention implementation with individualized feedback in the comfort of their own home at times convenient for their schedule and quality barriers by more closely resembling scenarios clinicians will encounter with their clients than contrived practice opportunities. The proposed customizable VR technology has the potential to (a) be highly impactful for healthcare professionals by teaching sustainable behavioral strategies for addressing severe behavior in the home and community, (b) be efficient and informative for trainers to collect data to support their trainees, (c) contribute to improved child treatment outcomes by preparing clinicians to implement intervention during treatment challenges, and (d) promote greater job satisfaction and long-term retention of healthcare professionals serving children with autism.

Walter Zahorodny, Ph.D.	Rutgers University	Detection & Connection – ASD Screening Project
Description: Every year, more children are identified with Autism Spectrum Disorder (ASD). Most ASD children are diagnosed after 36-months. Children from low income and minority communities are less likely to be evaluated for ASD and less likely to get early intervention program services than affluent and white children. To improve the early identification of young children with ASD and their linkage to services, we propose to implement a new service delivery program, Pediatric Detection + Connection (Ped-D+C) at multiple pediatric programs including primary care clinics, early intervention programs and Women, Infants and Children (WIC). We initiated the Ped-D+C program at a large pediatric primary care practice in Newark. The program was effective in increasing ASD screening and referral to EIP and development specialists. The program used a brief autism screener, the Psychological Development Questionnaire (PDQ-1) as part of the intake and continuity care process and engaged Mom2Mom – a peer support organization to facilitate linkage to early intervention services and comprehensive developmental evaluation. Mom2Mom is a peer-to-peer counseling system staffed by mothers of children with special needs who use their experience on behalf of parents of children who are screen positive. This project will address primary weakness in the process of early ASD identification including detection of ASD using a valid effective screener (PDQ-1) and connection by linking families of at-risk children to services through peer-to-peer support (Mom2Mom). The goals of the study are 1) to increase ASD screening in underserved populations, 2) facilitate linking of at-risk children to EIP services and comprehensive developmental evaluation, 3) reduction of wealth and race-based disparities in ASD identification and 4) provision of evidence regarding the effectiveness of the (Ped-D+C) model.

FY2025 Clinical Research Pilot Projects

Name	Institution	Project Title
Allison Curry, Ph.D., M.P.H.	Children's Hospital of Philadelphia	The Empowering Transport among Autistic Adolescents (ETA) Virtual Program for NJ Autistic Adolescents and their Caregivers.
Description: The transition to adulthood for autistic adolescents is a complex process with a unique set of challenges for independent living, employment, and social engagement. Being able to travel independently—whether by personal vehicle, public transit, rideshare, bicycle, or foot—has great potential to increase opportunities for work, play, and employment; ultimately, this may improve autistic teens’ well-being and health. Prior research in New Jersey has found that independent mobility (both driving and other forms of transportation) is an important topic to many autistic teens and their families. However, it is clear that more high-quality support is needed: the proportion of families with autistic teens interested in driving (two-thirds) is much higher than the proportion who get licensed (one-third); parents report spending “enormous” amounts of time—unsuccessfully—searching for resources to help them determine ideal mobility options for their child; and transportation is a major barrier to community engagement for those who don’t pursue driving. Thus, there is a critical need to develop resources and supports to facilitate independent mobility among both driving and nondriving autistic adolescents. With a strong evidence base in place, the long-term goal of this research program is to develop evidence-based interventions and tools that promote independent mobility, and therefore quality of life and health, among autistic adolescents and young adults. The overall objective of this proposed Clinical Research Pilot Project is to develop the web-based Empowering Transport among Autistic Adolescents (ETA) program. The project team is ideally suited to achieve this objective as we have been conducting research on the issue of autism and driving, particularly in NJ, for over a decade. The project has two specific aims. First, we will work closely with established project partners to create evidence-based content for 4 interactive modules that will be included in the ETA program: Preparing for Independent Mobility; Assessing Driving Readiness, Learning to Drive, and Nondriving Mobility Options. Second, we will work with a full-service web design and development agency to develop and evaluate a clickable prototype of the web-based ETA program platform. Specifically, the team will create initial concept designs and then clickable prototypes of the program’s web-based platform; the platform will be designed so that evidence-based tools that the team is developing in complementary projects can be seamlessly integrated into the program.

Kurin Suri, M.D.	Joseph Sanzari Children's Hospital (HMH)	Can a Novel, Multidisciplinary, Longitudinal Screening Process Lead to Earlier ASD Diagnosis in a Racially and Socioeconomically Diverse Population of ASD At-Risk Children?
Description: Newborns requiring Neonatal Intensive Care Unit (NICU) hospitalizations are at higher risk for Autism Spectrum Disorder (ASD) than healthy term infants and are the ideal target population for early diagnosis and intervention. We propose to determine if a longitudinal and multidisciplinary monitoring effort could help clinicians identify ASD by age two years, earlier than the norm. Although signs of ASD can be identified earlier, in New Jersey, the average age of diagnosis of ASD is 4 years and 9 months of age. We hypothesize that an accurate diagnosis – perhaps as early as two years of age – can be made in this high-risk population, which will lead to earlier treatment, and, thus, better outcomes for these children and their families. The increased risk of ASD in NICU graduates is believed to be related to a complex array of biological, genetic, and environmental risk factors, such as preterm birth, neurological injuries, and medical complications, as well as disruptions to the social environment that adversely impact healthy brain development. NICU graduates at the greatest risk for medical and developmental concerns are closely monitored in the first years of life in the NICU Follow-Up Program. While it is recognized that these children are at high-risk for ASD, signs of early atypical social-behavioral functioning may be overlooked in busy NICU Follow-Up Programs due to complex clinical presentations. Additionally, many NICU graduates also have identified motor delays, although little is known about the relationship between early motor delays and ASD in this population.

FY2024 Fellowship Research

Name	Institution	Project Title
Mengmeng Jin	Rutgers University	Modeling Microglial Dysfunction with Human iPSC Models of Down Syndrome and Autism Spectrum Disorder.
Description: Up to 39% of Down syndrome (DS) individuals have autism, or autism spectrum disorder (ASD) (hereafter referred to as DS-ASD), compared to 1% in the typical population. As the brain's resident immune cells, microglia play vital roles in regulating inflammation in the brain and shaping brain development, thereby impacting cognitive functions. Notably, dysregulation of microglial functions is highly associated with the development of ASD. This fact has driven researchers to investigate causal links between microglial dysfunction and ASD. However, very limited information is available on the precise contributions of microglia during brain development in ASD and DS-ASD, as well as the underlying molecular mechanisms. Recent advance in stem cell technology allows researchers to differentiate human induced pluripotent stem cells (hiPSCs) into microglia, which provides unlimited human microglial cells to study their pathophysiology. In this study, we will generate microglia from hiPSCs derived from DS individuals. We propose transplanting the DS human microglia into the mouse brain to further develop a human-mouse chimeric brain model. This new model will allow us to interrogate the pathogenic role of microglia in DS-ASD, by studying the DS human microglia developed in an intact brain environment. Findings from this study may lead to the development of new therapeutic treatments for not only ASD in the DS population but also ASD in the general population.

Luka Turkalj	Rutgers University	Perturbation of Neuronal Proteostasis and Integrated Stress Response in Cc2d1a and Cc2d1a/Cc2d1b Loss of Function.
Description: This study aims to investigate how problems with the way brain cells traffic and degrade proteins and respond to protein accumulation can cause neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). It focuses on an important protective pathway called integrated stress response (ISR), which is getting recognized as a common deficit in different disorders associated with ASD and ID. The re-searchers will be studying a gene called CC2D1A, which can cause these disorders when it is not working cor-rectly. They will use brain cells called neurons, which have been modified to not have this gene to study how it affects them. The researchers have three goals for this study: 1) to see how CC2D1A and another gene called CC2D1B help traffic proteins through neurons for degradation, 2) to see how the ISR responds when these genes are not working properly, and 3) to see if there is a connection between protein accumulation and ISR activation in these neurons. The integrated stress response is a promising therapeutic target that could be used in the treatment of different disorders associated with ASD and ID. Therefore, this research could help us to better understand how these disorders develop and aid in developing novel treatment strategies.

Le Wang	Rutgers University	Dissecting the circuits mechanism of ASD-associated NLGN3 and NRXN1 loss-of-function human neurons engrafted in a chimeric mouse model.
Description: Autism spectrum disorder (ASD) is a complex neurological condition that affects millions of individuals worldwide. According to the CDC, in New Jersey, the rate of ASD is 1 in every 35 children. The underlying causes of ASD are not well understood, but recent research has suggested that certain genetic mutations increase the risk of ASD in the population. According to Simon Foundation Autism Research Initiative (SFARI), mutations of both NLGN3 and NRXN1 have been linked to ASD. These genes are involved in the formation and function of synapses, the connections between neurons in the brain. In my recent publication, I found that a mutation in NLGN3 that linked to ASD caused aberrant functional changes in a human neuronal model. In this application, the overarching goal of this project is to unravel the mechanisms underlying ASD-associated mutations in NLGN3 and NRXN1 in human neuronal models. I hypothesize that loss-of-function mutations in NLGN3 and NRXN1 lead to a functional deficit in synapse formation and/or function. To test this hypothesis, I will generate functional human excitatory neurons with mutations in both NLGN3 and NRXN1. These neurons will then be engrafted into the prefrontal cortex of chimeric mice, allowing us to study their integration into the mouse brain circuitry. We will use advanced techniques to investigate the synaptic connectivity, activity, and plasticity of the NLGN3 and NRXN1 loss-of-function human neurons compared to control neurons. Utilizing this unique human neuron-mouse chimeric model, we will be able to address the long-term impact of human neurons carrying NLGN3 or NRXN1 mutations in an in vivo environment of neurocircuits. This study has the potential to provide significant implications for the development of effective treatments for ASD, as it will provide critical insights into the cellular and circuit-level mechanisms underlying the condition. Moreover, the use of a chimeric mouse model provides a valuable tool for further investigating the underlying causes of ASD and testing potential therapeutic interventions.

Ellen Wilkinson	Rutgers University	Adapting an evidence-based behavioral activation treatment for depression in minimally verbal autistic adults
Description: There is increasing attention to the mental health of autistic people, including research on treatments for disorders like depression. In fact, depression is thought to be even more common in autistic individuals, with prevalence estimates of 23-37% (Hollocks et al., 2019) and at least as common in individuals with intellectual disability (Buckles et al., 2013). Therefore, it is concerning that even though 20-30% of autistic people remain minimally verbal (MV) into adulthood (Howlin et al., 2014; Pickles et al., 2014), there has been very little attention given to the treatment of depression in these people and there are no treatments supported by research. There is one form of depression treatment that has shown promise in being a good fit for people with autism and/or intellectual disabilities: behavioral activation. This treatment does not heavily rely on cognitive and verbal communication abilities, like traditional mental health treatment does. BeatIt is a treatment that uses behavioral activation to treat depression in adults with intellectual disability (Jahoda et al., 2015). It has a focus on identification of pleasurable and meaningful activities, as well as increasing those activities. It includes a support person, who comes to all sessions and when appropriate assists with the activities. Because of these core features, with some adaptation it may be a good depression treatment option for MV autistic adults. The goal of this study is to adapt the BeatIt treatment manual to for use with MV autistic adults and then examine the feasibility of the treatment through a trial. Through collaboration with an interventional development group (3 MV autistic adults and their supporters) and the study team, an adapted manual will be developed (BeatIt-MV). Next, a feasibility trial including 12 MV autistic adults and their supporters will be conducted. To assess any changes, they will complete measures on their mental health and quality of life before, halfway through, and after the treatment. Participants will also provide feedback on the study procedures and treatment. Information collected during both parts of the study will be used to guide future studies to determine whether Beat-MV can be used to treat depression in MV autistic adults. This study is an important step toward addressing the mental health needs of MV autistic adults and supporting their quality of life.

FY2025 Fellowship Research

Name	Institution	Project Title
Hanna Caiola	Rutgers University	The role of MARK2 in neuronal hyperexcitability associated with Autism Spectrum Disorder
Description: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is behaviorally defined by social and communication deficits and repetitive behaviors. In addition, a large proportion of ASD patients suffer from co-occurring conditions such as cognitive impairment and epilepsy, which suggests that these disorders exhibit pathological commonalities at the cellular and molecular levels. For instance, both ASD and epilepsy are associated with abnormal increases in neuronal excitation; however, the molecular mechanisms underlying neuronal hyperexcitability in these disorders is unclear. Microtubule affinity regulating kinase 2 (MARK2) has been indicated as an ASD-risk gene through loss-of-function mutations and has also been linked to other neurodevelopmental disorders with comorbid epilepsy. This is interesting because we recently found that MARK2 knockout mice (MARK2 loss of function mice) exhibit ASD-like abnormalities including learning and memory deficits, reduced sociability, and synaptic dysfunction. Moreover, we found that reduced levels of MARK2 in mice also increases the susceptibility for seizures. Seizures commonly result from too much excitation in the brain. Therefore, the presence of seizures with MARK2 reduction suggests there is underlying neuronal hyperexcitability in these mice. Furthermore, these data suggest that loss of MARK2 may contribute to ASD and epilepsy by producing an abnormal increase in neuronal excitability. Nonetheless, the fundamental mechanism by which MARK2 regulates neuronal excitability is completely unknown. This proposal aims to test the hypothesis that MARK2 regulates neuronal excitability through modulating gene expression. Establishing the fundamental mechanism by which MARK2 regulates neuronal excitability will give insight into processes that become pathological in ASD and epilepsy.

Caroline Freden	Montclair State University	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: Autism is a diverse lifetime neurodevelopmental condition in which one in 35 New Jerseyan eight-year-olds are currently diagnosed. Every day, nonautistic “laypeople” called “Community Helpers” interact with autistic individuals. Society’s autism knowledge can be limited, even misguided, and stigma against autism can be high. Neurodiversity emphasizes the uniqueness of all brains, and neurodiversity-affirming interventions are those that seek to foster a two-way relationship between autistic and non-autistic people by promoting strengths and fostering growth at the same time, in a manner that aligns with what autistic people want and need. Autism trainings have been created for many people with the goal of increasing knowledge and decreasing stigma. However, it is important to seek input from and collaborate with the autistic community throughout the research process, an action known as participatory research. This will make sure that the products of research are meaningful for autistic individuals and increase their quality of life. The proposed project uses participatory methods to create and implement a neurodiversity-affirming autism training for non-autistic Community Helpers that will involve role-playing and will measure the impact, liking, ease, and approval of the training.

FY2024 New Jersey Autism Center of Excellence

Name	Institution	Project Title
Wayne Fisher, Ph.D.	Children’s Specialized Hospital	New Jersey Autism Center of Excellence.
Description: Given the complex presentations and causes of ASD, the variability in response to treatment, and the disparities in clinical services, there has been increased emphasis on the importance of interdisciplinary, translational research informed by the needs and input of individuals with ASD and their families. In this application, we propose to address these complex and unique features of ASD by promoting increased communication and collaboration amongst autism researchers, educators, practitioners, and autistic individuals and their families to (a) improve our understanding of and ability to diagnose and treat ASD, (b) decrease service disparities, and (c) improve health outcomes for all New Jersey individuals and families affected by ASD. The proposed NJACE will facilitate the development of enduring training programs on biomedical treatments and diagnosis of autism for physicians and other healthcare professionals by awarding seed grants (n = 2) to New Jersey investigators to support the development of competitive federal training grants (e.g., T32 applications to NIH). We will facilitate specialized, science-to-practice training in autism diagnosis and management by offering practica and workshops in critical areas of need and by awarding competitive training stipends so that current and future healthcare professionals serving community-based organizations can receive the specialized training, with priority given to healthcare workers serving marginalized groups. We will disseminate critical information and provide continuing education on the latest advances in biomedical research on autism for physicians and other healthcare professionals through an annual conference and bimonthly symposia that will include leading local and national experts in the field. The proposed NJACE, in cooperation with CSH and the Rutgers Clinical Trials Office, will develop a statewide ASD research online database that will facilitate communication between New Jersey researchers and individuals with ASD and their families so that (a) the ASD community receives up-to-date information on the latest scientific advances related to ASD, (b) those affected by ASD can provide direct input and collaboration with researchers to increase the impact and relevance of future research, (c) individuals with ASD and their caregivers will have the opportunity to participate in research, and (d) New Jersey researchers will have increased access to potential research participants. The proposed NJACE will prioritize applications for its research and training grants and presentations for its informational and continuing-education activities that focus on the following: (a) transition to adulthood, including health care, educational pursuits, and employment; (b) developmental support services (e.g., early identification, co-occurring ID); (c) use of data to drive measurable health improvements; (d) identifying and targeting vulnerable populations for interventions to address health disparities; and (e) promotion of collaboration across sectors to develop health policies and achieve health equity.