Research

Postdoctoral Research Experience
PI: Dr. Alexander Ophir | Dates: January 2019 – Present 
Department of Psychology, Cornell University, Ithaca, NY

As a postdoctoral fellow in the Ophir lab, I have begun studying the role of the lateral septum (LS) in regulating affiliative, aggressive, and social bonding behaviors in sex-naive and pair-bonded prairie voles using pharmacology, chemogenetic tools, and several ethologically relevant behavior tests for assessing social behaviors. Our study will show that LS activation alters behavior that is dependent on pair-bonding status and social contexts. We are currently preparing a manuscript for publication, stay tuned! Results from this study has led me to question the influence of LS projections to other brain regions that are important for social aggression, such as the ventromedial hypothalamus (VMH). By combining Cre-dependent DREADDs with the retrograde viral vector, I am working to assess how LS terminals at the VMH alter social affiliation, pair bonding, and aggression as a function of pair bonding status. Additionally, my experience with examining epigenetic mechanisms in pair bonding has led me to develop and validate a method in the Ophir lab to modify LS-specific DNA methylation at the vasopressin receptor (avpr1a). 
 
Our current pre-print in BioRxiv highlights age-related genome-wide DNA methylation changes in sex-naive and pair bonded males and females in a collaborative project with Dr. Steve Horvath. For the first time, this study enabled assembly of highly accurate multi-tissue age estimation methods (epigenetic clocks) for prairie voles that apply to the entire life course and examine the impact of pair-bonding on aging. We built a dual species human-vole clock to show that epigenetic aging mechanisms are highly conserved between prairie voles and humans. According to our human-vole clock of relative age, both male and female sex-naive voles exhibit
accelerated epigenetic aging in brain regions within the pair bonding circuit, when compared to pair bonded voles of the same chronological age. Epigenome wide association studies identified CpGs in genes that were strongly associated with pair bonding across the three tissue types that we sampled (brain, ear, and live) and in genes that exhibit a convergent methylation change between pair bonding and aging. For the first time, our study describes highly accurate DNA methylation-based estimators of age in prairie voles and provides evidence that pair bonding status modulates the methylome.

March 14, 2022 Update:
I recently got awarded a postdoctoral fellowship training grant from the National Institutes of Health (NICHD F32 Postdoctoral NRSA). I will have the privilege to be co-sponsored by Dr. Alex Ophir and Dr. Lauren O'Connell for the next three years. This training award will allow me to investigate the Impact of paternal care on stress-coping behaviors and neuropeptide systems. Heightened sensitivity to stress can lead to maladaptive coping behaviors, such as social withdrawal and aggression. Children that experience early life adversity (ELA) have an increased risk of developing similar difficulties. ELA triggers enduring effects via modifications to DNA methylation that may persist into adulthood and potentially escalate vulnerability to early-onset forms of neuropsychiatric disorders. Notably, the impact of paternal care and the neuroendocrine factors that are involved in responsiveness to later life stress in offspring are vastly understudied, due to the lack of animal models that exhibit bi-parental care. To this end, prairie voles will be used to model the impact of paternal care on offspring stress sensitivity. Paternally deprived prairie voles develop to exhibit deficits in pair bonding, and region-specific and sex-specific modifications in oxytocin (OT) and vasopressin (VP) receptor expression. OT and VP are essential neuropeptides that modulate social behaviors. However, epigenetic modifications of the OT and VP receptor genes in response to ELA have not been well characterized. I plan to integrate multiple levels of analysis (behavioral, epigenetic, cell-specific gene and protein profiling, and neuronal function) to reveal the impact of paternal deprivation on prairie vole offspring that experience chronic social defeat stress and to assess its collective influence on the OT and VP systems and behavioral responses. From a developmental perspective, this ecologically relevant two-hit model of stress will be essential for understanding the relationship between real-world experience and brain and behavior function, and potentially inform novel therapeutic strategies against stress-induced maladaptive responses.

Graduate Research Experience
PI: Dr. Mohamed Kabbaj | Dates: August 2013 – December 2018
Program of Neuroscience, Department of Biomedical Sciences, Florida State University, Tallahassee, FL

While my undergraduate research experience is irreplaceable, my attention to scientific discovery always leaned in the fields of biology and psychology. I joined Dr. Kabbaj’s laboratory at Florida State University when I heard about his seminal work when he demonstrated a role of histone modifications at specific genes the underlie the initiation of social bonding in prairie voles. The prairie vole (Microtus ochrogaster) is a highly affiliative rodent species known to form long-lasting monogamous pair bonds, display pair bonding-induced aggression, and exhibit bi-parental care. These distinctive intraspecific social behaviors make the prairie vole a valuable animal model for understanding the neurobiology of social behaviors. For my dissertation work (Sailer et al., Sci Rep, 2019), I developed a model in which prairie voles are prenatally exposed to valproic acid (VPA) to examine how development of social behaviors are impaired by epigenetic influences. VPA is a histone deacetylase inhibitor (HDACi) that is widely used as an anticonvulsant. However, VPA is teratogenic and its administration during pregnancy significantly increases risk of autism spectrum disorder (ASD). I demonstrated that prenatally VPA-exposed prairie voles exhibit social interaction impairments, along with enhanced anxiety-like behavior with some subtle sex differences. Prenatal VPA exposure reduced expression of the vasopressin receptor (avpr1a) and methyl CpG binding protein 2 (mecp2) genes in the medial prefrontal cortex (mPFC), a brain region implicated in complex cognitive  and social behaviors. Surprisingly, VPA-exposed subjects displayed a robust preference for their partners over strangers and showed high levels of aggression against intruders. This study allowed me to highlight an important distinction between social affiliative behaviors and the underlying processes of an enduring social attachment between sexes—a distinction observed in a subset of the ASD population.

In collaboration with Dr. Zuoxin Wang, my graduate work included other projects that investigated the underlying molecular processes of social monogamy. I led a study that investigated differences in peripheral testosterone and neuronal network activity in male prairie voles that adopt varied mating tactics, which allowed me to make the distinction between social monogamy and sexual infidelity. This project gave me an opportunity to learn and employ in situ hybridization to examine whole-brain neural activity-dependent changes and ELISA to measure serum testosterone modifications in prairie voles that adopt different mating tactics. I also learned to use chemogenetic tools to manipulate neural activity in brain regions important for social monogamy.
 
I continued to learn and sharpen my behavioral and molecular skills while assisting a postdoctoral fellow in the Kabbaj lab to examine transcriptomic profiles of prairie voles during the initial and late phases of pair-bonding. This work has been published in the journal Biological Psychiatry. Additionally, I collaborated in a project that showed epigenetic regulation, through DNA methylation, can be responsible for neuroadaptations induced by drugs of abuse. Projections from the medial prefrontal cortex (mPFC) to the nucleus accumbens (NAc) are critical for cocaine reinstatement because they undergo cocaine-induced epigenetic modifications. In our hands, optogenetic inhibition of mPFC-NAc projections blocked reinstated cocaine-seeking behavior. Correspondingly, methyl supplementation attenuated cocaine-seeking behavior and reversed methylation patterns of the immediate early gene c-Fos, suggesting that MET may act by altering the excitability of mPFC-NAc circuitry during cocaine-primed reinstatement. This body of work greatly contributes to the field of translational neuroscience because it reveals the contribution of epigenetic mechanisms in the modulation and maintenance of gene expression and behavior. 
 
My time in Dr. Kabbaj’s lab has resulted in 5 training fellowships and scholarships for underrepresented minorities in Neuroscience, several presented abstracts at local and national conferences, and 7 travel awards. My various research projects during my graduate training have resulted in 3 first-authored publications (2 published and 1 in preparation for submission) and 2 co-authored publications (1 published and 1 submitted to Biological Psychiatry). Overall, these projects provided me a strong background in molecular techniques and gave me a solid conceptual foundation for receptor-specific mechanisms underlying vasopressin and oxytocin regulation of pair bonding. 
 

Undergraduate and Post-Baccalaureate Research Experience
PI: Dr. Radha Pyati | Dates: August 2009 – December 2011
Department of Chemistry, University of North Florida, Jacksonville, FL

My research experience began as an undergraduate student at University of North Florida (UNF) in Dr. Radha Pyati’s environmental chemistry laboratory. I aided in optimizing a protocol to capture and quantify morphological changes in fission yeast (Schizosaccharomyces pombe) through the employment of imaging flow cytometry (IFC). The predicted changes in morphology known to accompany treatment following a range of DNA damaging agents and cytoskeletal toxins was successfully achieved through our novel protocol. This experience allowed me to learn fundamental cell culture techniques, how to set up and use an imaging flow cytometer, and how to optimize a protocol for the analysis of morphology-induced changes to S. pombe by exposure to various cytoskeletal toxins. The results of this research were published in a manuscript in which I contributed to write and revise (Pyati et al., J Yeast Fungal Res, 2011). While writing and editing the manuscript, I also wrote and presented an oral proposal for funding to the UNF Student Government. The funds that I successfully received from the UNF Student Government paid for my travel to the 2010 Pittcon Conference & Expo where I gained first-hand experience in presenting a poster at an international scientific conference. 

My enthusiasm for research granted me the opportunity to continue to work in Dr. Pyati’s lab as a Research Assistant after completing my undergraduate education. I aided in selecting compounds from the National Cancer Institute (NCI) Natural Products Repository that are known to be used as therapeutic agents. I observed and characterized the ability of these products to alter the morphology of S. pombe through IFC, and some of my data was published in my second undergraduate student publication (Heisler et al., Nat Prod Bio, 2014). Gaining a full understanding of the mechanisms of action of natural products as therapeutic agents includes observing the effects of natural products on cellular morphology, because abnormal cellular morphology is an important aspect of cellular transformations that occur as part of disease states, such as cancer. In addition to concentrating on my research, I also trained incoming undergraduate students cell culture techniques, how to operate and maintain the imaging flow cytometer, and how to analyze and interpret data. Altogether, my exposure to scientific research in Dr. Pyati’s lab was monumental in shifting my career aspirations. These experiences (learning research techniques, applying for funding support to travel in order to present my research at a conference, writing and presenting my research, and receiving feedback from mentors and peers) provided me with a valuable impression of how graduate school and academic research functions, and drove me to focus my career and educational ambitions to pursue a career in academia.