Postdoctoral research project
2024 - Present
The role of early life stress and maternal presence on olfactory sensory neuron development
Mentor: Bianca Jones Marlin, PhD
Columbia University's Zuckerman Institute, New York, NY
Exposure to stress during early life has been shown to impact the development and wiring of neural circuits necessary for adaptation and survival throughout the lifespan. For example, maternal neglect during early postnatal life has been linked to alterations in neural circuits involved in stress regulation and emotional processing. In contrast, maternal presence during an adverse event can alleviate the stress response in offspring, a phenomenon known as maternal social buffering. While this seems beneficial, it may inadvertently blunt the development of adaptive circuits required for survival. Studies from the Marlin lab have demonstrated that odor-shock pairing increases the generation of olfactory sensory neurons responsive to the conditioned odor, promoting adaptation and survival to the environment. We therefore hypothesize that maternal social buffering will attenuate this adaptive response in pups, which may consequently impact their stress resilience in adulthood.
These studies will use whole-brain tissue-clearing and high-resolution imaging techniques to quantify the number and morphology of odor-encoding neurons within the main olfactory epithelium. Behavioral measures will be automatically tracked and obtained using machine-learning approaches, including keypoint-MoSeq and DeepLabCut. Lastly, in collaboration with Dr. Ofer Yizhar's group, we will use transcranial optogenetics to inhibit oxytocinergic signaling in awake, freely behaving pups to determine how oxytocin, a neuropeptide crucial for social bonding, modulates avoidance behaviors following early life odor-shock pairing with maternal presence. In summary, these experiments will provide a mechanistic understanding of how oxytocin and maternal social buffering impact olfactory sensory neuron development and stress adaptation.
Doctoral dissertation project
2019 - 2024
The effects of the 16p11.2 deletion and early life microbial alterations on hippocampal neurogenesis and behavior
Mentor: Emanuel DiCicco-Bloom, MD
Co-mentor: Martin J. Blaser, MD
Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
Infancy is a critical period of development when the gut microbiome-brain axis is exquisitely sensitive to genetic risk and environmental exposures. Such alterations during early life have been linked to adverse health outcomes and neuropsychiatric conditions. These studies utilized a gene by environment (GxE) model to examine how an altered microbiome affects neurodevelopment and behavior, and if identified alterations were exacerbated by genetic constitution. Wildtype and 16p11.2 deletion (16pDel) male and female mice were exposed to a brief, low-dose course (relevant to human childhood exposure) of a cephalosporin antibiotic, cefdinir, on postnatal (P) days 5-9, followed by sacrifice at various developmental timepoints. The 16pDel mouse was chosen to model genetic vulnerability due to its significant implications in neurodevelopmental disorders. At P13, we observed successful perturbations to the microbiome in all cefdinir-exposed mice, with accompanying changes in sera lipids and metabolites. However, there was a unique GxE effect in hippocampal gene expression and stem cell proliferation of cefdinir-exposed 16pDel males. This effect was accompanied by a compromised intestinal barrier in 16pDel males, revealed by increased intestinal permeability in vivo. To determine if the microbial and neural alterations following early life cefdinir exposure persisted or recovered, we extended our characterizations to P21. Although the gut microbiome began to recover by P21, there were numerous alterations in hippocampal gene expression in all cefdinir-exposed mice suggesting disorder progression, with the most robust changes in 16pDel males. Lastly, to assess the impact of early life cefdinir exposure on behavior, we conducted a longitudinal behavioral paradigm from P21-P89. Across three cohorts, we observed decreased juvenile sociability, compromised risk-aversion behaviors, heightened social preference, and impaired associative learning in cefdinir-exposed mice. Taken together, this work highlights the progressive impact of early life microbial alterations on brain development and behavior and provides the novel discovery that genetic constitution influences the subsequent changes in hippocampal gene expression and neurogenesis. This work is currently in preparation for publication.
Pre-dissertation project #2
2018-2019
Autism NPCs from both idiopathic and CNV
16p11.2 deletion patients exhibit dysregulation
of proliferation and mitogenic responses
Mentor: Emanuel DiCicco-Bloom, MD
Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
Postmortem and neuroimaging studies have identified no consistent abnormalities in the autistic brain; however, they have uncovered an overall dysregulation of early brain development. Multiple lines of evidence suggest that neural precursor cell (NPC) proliferation may be affected and recent advances in induced pluripotent stem cell (iPSC) technology now permits the ability to investigate this process. This study hypothesized that NPC proliferation may be affected in different subgroups of autism. The central findings reported hyperproliferation in NPCs from three macrocephalic individuals and hypoproliferation in two idiopathic autism cases, which were inversely correlated with P-ERK levels (Hyperproliferative, lower P-ERK, hypoproliferation, elevated P-ERK). My contributions involved determining an effective concentration of an ERK1 agonist and antagonist to use in cultures of multiple NPC lines to determine if the hypo/hyper proliferation phenotype could be rescued. I received training in creating and maintaining NPCs, basic pharmacology principles, thymidine incorporation assays, and immunocytochemistry. The results of this study have been published in Stem Cell Reports.
Pre-dissertation project #1
2018-2019
Measurement of subcategories of repetitive
behaviors in autistic adolescents and adults
Mentor: Vanessa Bal, PhD
Restricted and repetitive behaviors (RRBs) are features necessary for the diagnosis of autism and are assessed at all ages. It cannot be assumed, however, that instruments designed for assessing children are appropriate for use with older individuals. This study explored the hypothesis that the Autism Diagnostic Interview-Revised (ADI-R) and the Repetitive Behavior Scale-Revised (RBS-R) questionnaires, which are used to evaluate RRBs in children, could also be used in adolescents and adults. My specific role included analyzing existing data from autistic adolescent and adults assessed using ADI-R, RBS-R Caregiver, or RBS-R Self-Report, to determine the relationships between items on each instrument, whether items were meaningfully related to support categories of RRBs, and whether instrument subscales were related to age and nonverbal intelligence. I presented this work at the International Society for Autism Research meeting (INSAR) in May 2019 and published it in Autism in Adulthood. The central findings provided support for use of the RBS-R Caregiver and Self-Report, but not the ADI-R for assessing RRBs in adults. This helps to inform clinicians and researchers about methods available to assess RRBs in autistic adolescents and adults.
Rutgers University, Piscataway, NJ
Undergraduate thesis project
2014-2018
Cholesterol-lowering drugs alter brain steroid
levels in a songbird model system
Mentor: Carolyn Pytte, PhD
CUNY Queens College, Flushing, NY
Cardiovascular diseases are one of the leading causes of death in the United States and this statistic underscores the widespread prescription of statin drugs. These drugs are highly effective in lowering plasma cholesterol but can also cross the blood-brain barrier and decrease cholesterol synthesis in neurons and glia. Moreover, the FDA has approved the use of statins for treating children as young as 8 years old who have a genetic risk for developing the autosomal dominant disorder familial hypercholesterolemia, despite there being minimal research on the neural, cognitive, or neuropsychological effects of statins in children. The objective of my undergraduate thesis project involved testing the hypothesis that statins would decrease brain-derived steroids, including estradiol, which is derived from cholesterol and functions in memory. This project required me to develop the procedures necessary to isolate and quantify steroids from brain tissue, a technique novel that was novel to the lab at the time. My efforts to overcome this intense but rewarding troubleshooting resulted in a first author published abstract at the 2017 SfN meeting, which was funded by the Faculty for Undergraduate Neuroscience Travel Award. My data revealed sex-dependent hemispheric differences in the effects of statins, which may contribute to sex differences observed in cognitive deficits in clinical populations.
Summer undergraduate
research experience #2
Summer 2016
Using high-throughput screening techniques
to uncover the molecular mechanisms
of synapse elimination
Mentor: Beth Stevens, PhD
Boston Children's Hospital, Boston, MA
A research topic that fascinated me as an undergraduate student was neuro-immune interactions during healthy development and disease. In the Stevens lab, I assisted postdoctoral scholar, Allie Muthukumar, in demonstrating that a cell-based high-throughput screening (HTS) assay could be used as a tool to understand the molecular mechanisms of synapse elimination. I received training in culturing mouse primary microglia and isolating synaptosomes, how to use state of the art technology (HTS ArrayScan), and pharmacology principles used to test various drug library compounds.
Summer undergraduate
research experience #1
Summer 2015
The effects of growth factor stimulation
on neurite extension in autism
patient-derived neural stem cells
Mentor: Emanuel DiCicco-Bloom
I applied and was accepted as 1 of the 12 students in the R25 NIH-funded Summer Undergraduate Research Program (SURP) in Neuroscience at Rutgers University. The goal of my summer project was to test the hypothesis that autism-derived neural precursor cells (NPCs) would have reduced neurite outgrowth in response to growth factor stimulation in comparison to their unaffected sibling’s NPCs. I was fascinated by this project due to its translatability to autism pathogenesis. I learned how to culture and experiment on NPCs derived from induced pluripotent stem cells and quantify neurite outgrowth using fluorescent microscopy. My findings supported the hypothesis, revealing that autism NPCs displayed reduced sensitivity to growth factors compared to their matched sibling NPCs. This work resulted in two middle authorship abstracts -- one for a SfN nanosymposium presentation and the other for the International Society for Autism Research (INSAR) meeting.
Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
COURTNEY R. MCDERMOTT, PhD