Sasha Fulton, Ph.D.

EDUCATION

Columbia University Zuckerman Institute
Postdoctoral Fellow - Present

Mount Sinai Icahn School of Medicine 
Ph.D. in Neuroscience - 2022

City University of New York, Hunter College
M.S. in Molecular Biology - 2016

Columbia University
B.S. in Neurobiology - 2011

RESEARCH EXPERIENCE

Columbia University Zuckerman Institute of Mind, Brain, Body
April 2023 – Present
Postdoctoral Fellow
PI: Dr. Ishmail Abdus-Saboor                
                                                                                                           

Defining the differential role of Mrgprb4+ social touch somatosensory neurons in pain modulation and frontolimbic dysregulation during chronic inflammatory pain

  • Explore the molecular and cellular substrates that modulate central sensitization of chronic inflammatory pain in the brain’s limbic system using a combination of circuit-specific optogenetic manipulation, electrophysiological recording, fiber photometry, behavioral phenotyping, and multi-omic single nuclei sequencing to define skin-to-brain signaling in the context of chronic inflammatory pain and of the neural substrates underlying both the physiological and psychological domains of chronic pain.

Additional Projects:
-Role of Mrgprb4+ Social touch neurons in stress resilience
-Genetic basis of heightened pain sensitivity and vulnerability to opioid dependence
-Cellular mechanisms of nerve injury and repair

Mount Sinai Icahn School of Medicine Neuroscience Department
January 2017 – April 2023
Ph.D Student
PI: Dr. Ian Maze


Profiling cell-type specific chromatin accessibility in human orbitofrontal cortex implicates astrocyte dysfunction in MDD

  • Used chromatin accessibility profiling (ATAC-seq) of human postmortem OFC tissue from MDD vs. control individuals to characterize epigenetic regulation of astrocytic inflammation as a major component of the chromatin signature of MDD in the human OFC

  • Identified a novel chromatin regulator of inflammatory transcription in astrocytes, called ZBTB7A

  • Utilized a novel astrocyte-specific viral vector approach in combination with behavioral phenotyping, RNA-sequencing, and electrophysiology to demonstrate the direct role of this chromatin-based regulatory mechanism in astrocytic inflammation response 

  • Found that bidirectional Zbtb7a manipulation in mouse OFC astrocytes influences broad inflammatory and cell signaling gene expression changes that specifically mediate the plasticity of astrocytes and their ability to induce either a proinflammatory or an anti-inflammatory phenotype in response to stress

  • First author manuscript presenting this work is currently in revision and resubmitted at Neuron

Additional projects:
-Dopaminylation in Substance use disorder (one co-first author manuscript at Neuropsychopharmacology, one co-author publication in Science)
-Triplication of BRWD1 in down syndrome brain promotes epigenomic dysregulation and intellectual disability (one co-first author publication at Nature Communications)


Hunter College and Columbia University Medical Center, New York Psychiatric Institute 
Master’s Degree Student Research 
July 2015 – June 2016
PI: Dr. Jeremy Coplan and Dr. Todd Sacktor


Investigating the role of synaptic LTP, neurotrophism, and serotonergic dysfunction in cognitive deficits in Non-Human Primate models of affective disorder

  • I utilized expression levels of the atypical PKC isoform, PKMzeta, in the NHP brain as a novel marker of reduced cognitive plasticity and affective processing associated with affective disorder, specifically in the anterior hippocampus – a region characterized by increased serotonergic projections and high connectivity with the limbic system

  • Because BDNF release in the hippocampus is closely linked to both serotonin signaling and PKMzeta activity, I also explored my hypothesis that ELS causes serotonergic dysfunction, directly affecting BDNF neurotrophic activity and ultimately compromising PKMzeta function and LTP – my data demonstrates that this relationship may be a significant factor in the cognitive deficits associated with affective disorder following ELS. 

  • My first-author manuscript describing the results from this work has been published at Learning and Memory.


Columbia University Medical Center, New York Psychiatric Institute
Neurohistology Laboratory Research Director 
August 2012 – June 2016
PI: Drs. Jeremy Coplan, Tarique Perera, and John Mann

Abnormal serotonin neurotransmission predicated by early life stress mediates maladaptive neurotrophic changes in the non-human primate hippocampus

  • Utilized archived Non-human Primate (NHP) CSF samples to measure levels of monoamine metabolites and correlate with hippocampal volumetric analysis from structural imaging data in early-life stress vs. control animals

  • From these findings, I wrote a second-author manuscript with my PI (Dr. Jeremy Coplan), published in Frontiers of Behavioral Neuroscience, examining associations between Early Life Stress (ELS), serotonergic dysfunction, and reduced hippocampal volumes in NHP models

  • Designed and implemented IHC image analysis protocol using R and ImageJ software for multi-region analysis in NHP brain

  • Devevloped, optimized, and ran novel neurohistoimmunological protocols for detection of wide range of antigens in NHP brain tissues

  • Wrote and prepared R21, R01, and U01 grants for NIH submission

  • Trained and supervised over 12 research assistants, volunteers, and graduate students

  • Managed NIMH R01 grant administration, budget, contracts, and ordering, as well as daily operation of the laboratory 


Columbia University Medical Center, New York Psychiatric Institute
Research Assistant
PI: Drs. Jeremy Coplan, Tarique Perera, and John Mann
May 2011 – August 2012


Investigating the role of adult hippocampal neurogenesis in the antidepressant effects of fluoxetine in the non-human primate brain

  • Assisted in generating a NHP model of stress-induced MDD behaviors, including a two-hit model utilizing animals that had undergone early life stress (ELS) plus later adult separation stress (ASS)

  • Administered gamma radiation to ablate hippocampal neurogenesis (vs. sham) and subsequently administered the SSRI fluoxetine (vs. saline) via stomach intubation, in order to determine if neurogenesis was required for the antidepressant effect of fluoxetine

  • Assisted in creating a behavioral measures index which could be used to categorize aspects of monkey behavior (including affiliation, anxiety, anhedonia, and hierarchy behaviors). 

  • Used this index to characterize NHP behavior at baseline, post-neurogenesis ablation, post-stress, and post-SSRI treatment

  • Independently developed and optimized novel multiplexed IHC protocols to visualize specific markers of neurogenesis in post-fixed perfused NHP monkey tissues

  • Created a custom script built into ImageJ in order to quantify positively-labeled cells in conjunction with confocal microscopy 

  • The methodologies I developed allowed me to determine that fluoxetine stimulated rates of neurogenesis in the dentate gyrus, and that rates of neurogenesis correlated with behavioral measures of anxiety and anhedonia.

  •  In NHP postmortem tissues, I also used these methods to demonstrate that ELS was correlated with reduced dendritic complexity in adult-born neurons in animals treated with SSRIs, suggesting that ELS may contribute to treatment resistance. 

  • I am co-author on 8 separate manuscripts that have used these results to explore the relationship between various physiological measurements and behavioral aspects of cognitive flexibility in NHP models of MDD


Columbia University, Astrophysics Department 
Research Assistant 
July 2010 - January 2011
PI: Dr. Szbolcs Marka

Developing a low-cost infrared light-based optical barrier to divert Anopheles gambiae mosquito vectors from high density human areas to reduce the spread of malaria

  • Under a grant from the Bill and Melinda Gates Foundation, conducted independent research project studying effects of infrared light on the sensory systems and behavior of Drosophila and African mosquito

  • Independently started and managed both Drosophila and African mosquito colonies

  • Utilized the custom-built MATLAB package FlyWALKER in order to track and quantify the gait parameters in freely walking drosophila and freely flying mosquitoes before, during, and after exposure to the infrared-light “wall” with high temporal and spatial resolution

  • Using this system, I found that the infrared light averts the movement of both drosophila and mosquitoes, and that this aversion did not affect the ability of either insect to coordinate movement after exposure, suggesting that this technology could be utilized to develop devices for control of malaria vectors in high-risk areas for disease transmission

TEACHING EXPERIENCE

Mount Sinai Icahn School of Medicine

Teaching Assistant for Molecular Neuroscience Course (Fall /Spring 2018 – 2019)

  • Led weekly literature review seminar for first-year graduate students

  • Held weekly office hours and review sessions for exams 

  • Coordinated weekly faculty lectures and classroom logistics

  • Graded exams and papers 

AWARDS

Allison Doupe Fellowship, McKnight Endowment Fund - June 2024 

Research Distinction Graduation Award, Icahn School of Medicine Mount Sinai - May 2023

NIH Outstanding Scholars in Neuroscience Award Program (OSNAP) Recipient -  May 2022

Friedman Brain Institute Academic Scholar BRAIN Award - April 2018

Top Poster Award, Society of Biological Psychiatry Annual Conference - May 2016

TALKS AND PRESENTATIONS

NIDA Genetics & Epigenetics Symposium “Novel methodologies to untangle the epigenetic and transcriptional underpinnings of substance use disorder": Symposium Talk May 2024

Society of Biological Psychiatry Symposium “Uncovering Novel Drug Targets for Psychiatric Illnesses by Harnessing Large-Scale Genomic and Brain Omics Data” : Symposium Talk May 2023

Cell Symposia “Mechanisms of Psychiatric Disease”: Symposium Talk May 2022

Federation of European Neuroscience Societies Conference : Poster presentation July 2022

Society for Neuroscience Student Member (Presented posters at Annual SFN meeting 2016-2023)

Society of Biological Psychiatry Student Member (Presented posters at Annual SOBP meeting 2013-2017)


SKILLS

High throughput sequencing sample/library preparation and analysis: ATAC-seq, RNA-seq, ChIP-seq, Multiomic Single-cell and Single Nuclei- RNA/ATAC-seq

Cell sorting: FACS/FANs from brain tissue and in vitro culture, Magnetic-Activated Cell-sorting (MACs), activity-dependent markers, cell-type specific markers

In vivo calcium imaging: Inscopix microendoscopy for single-cell imaging with single or dual color, Fiber photometry for calcium activity and neuromodulator release. 

Rodent Experience:
Surgery: Virus injection, miniendoscope implantation, fiber photometry probe implantation into brain with stereotaxic surgery, Spared Nerve Injury and variants of this procedure (e.g. nerve crush/ligation) for modeling neuropathic pain, invtravenous catheterization for drug self-administration paradigm, ovariectomy, subdermal implantations, transcardial perfusion for IHC.

Techniques: Chemogenetic manipulation with DREADDs. Optogenetic manipulation in brain/skin.

Mouse Behavior: Social Defeat (chronic and subthreshold) Stressor, Restraint stress, Social interaction test, Operant reward learning paradigms, Reversal learning, Progressive Ratio tests of motivation, Sucrose preference test, Forced swim test, Open field test, Novelty suppressed feeding, Sucrose splash test, Fear Conditioning, Conditioned Place Preference, Self-Administration paradigms, mechanical stimulation, Hot-Plate Test, mouse breeding and timed pregnancy.

Rat Behavior: Juglar catherization surgery for intravenous delivery systems, Self-Administration paradigms (operant boxes) for cocaine, amphetamine, and sucrose; Reversal learning, Progressive ratio test, lesion studies

Cell culture: Primary cell culture – dissection of prenatal brain and culture of cortical and hippocampal neurons/co-cultures from both mouse and rat, primary human astrocytes (culture only), Dosal root ganglion tissue culture, N2a, Hela, HEK cell lines, viral treatment in vitro, IHC, luciferase assays in vitro, exosome isolation from cell media

Molecular and Cellular Techniques: Extraction of RNA/protein/DNA from human and preclinical tissues (including brain, blood, PBMCs, organs, bone marrow, sperm), PCR, qPCR, Western Blot, gel electrophoresis, restriction enzyme digestion, plasmid mini-prep techniques, transformation and cloning techniques, Gibson assembly, site mutagenesis, nuclear isolation, HPLC isolation of histones, histone acid extraction, cloning and packaging of lentiviral and AAV vectors for in vitro use

Neurohistology: Perfusion and fixation of brain tissues, cryostat sectioning, vibratome, antigen retrieval techniques for over-fixed or compromised tissues; microscopy imaging using bright field and fluorescent techniques; confocal microscopy; image analysis with ImageJ

Non-Human Primate Experience: Behavioral ratings and observation; administration of drugs via stomach intubations, intravenous and intramuscular injection; assisted in execution of procedures including fMRI imaging, irradiation of targeted brain structures; electrocardiography; intravenous saline perfusion of brain; removal and dissection of brain; post-fixation of brain. Conducted behavioral rating observations on three cohorts of non-human primates, Performed medical procedures on non-human primates – administering fluoxetine via stomach intubation, intravenous infusion of BrDU, and intramuscular injection of ketamine anesthesia, gamma irradiation of hippocampus, cisternal CSF sampling, electrocardiography, and fMRI imaging

Data Analysis and Software: ImageJ, Adobe Photoshop CS, Adobe Illustrator, Inkscape, Prism, Snapgene, Excel, AnyMaze, Galaxy, Cell Ranger,

R programming language to analyze sequencing datasets (e.g. Seurat for single-nuclei sequencing) including QC, alignment (e.g. HISAT2), quantification (e.g. featurecounts), differential expression/binding/accessibility (e.g. DESEQ2, MACs, Diffreps), and downstream analysis (e.g. RRHO2, GSEA, EnrichR, WGCNA).