Human stem cell expert in generating organoids for drug screening and regenerative medicine. We are at MIT's The Engine.

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My postdoctoral work has focused on metabolic changes in two neurodevelopmental disorder syndromes. 1) 16p11.2 Deletion Syndrome is a highly penetrant copy number variant associated with a heterogeneous array of neurodevelopmental and mental health disorders, including autism spectrum disorder. In order to study the syndrome modeled in zebrafish, I first established a new method to measure local field potentials in the CNS of unanesthetized live larvae by non-invasive multielectrode array. My approach to studying 16pdel was to explore the metabolic landscape in patient-derived neurons. I demonstrated that patient 16pdel induced pluripotent stem cell- differentiated neurons show augmented local field potential activity and altered ceramide-related lipid species relative to controls. In the complex syndrome, FAM57B has emerged as a candidate gene. Contrary to previous findings, we determined FAM57B is a ceramide synthase modulator. I propose a model whereby Fam57b functions to maintain normal plasma membrane physiology, necessary for proper formation and function of neurons in the developing brain. 2) An important aspect of Rett Syndrome (RTT) are the non-cell autonomous functions that are sparsely understood. I am investigating the connection between human RTT astrocyte attributed properties to neuronal dysfunction and brain development. Utilizing human embryonic stem cells (hESC) to model RTT, I am studying the development of the syndrome in stem cell-derived astrocytes, cortical neurons and cerebral organoids. I am examining how metabolic disruption and dysfunctional mitochondrial impact astrocytes and neuron function. I combine transcriptomic, proteomic, and metabolomic data to connect altered biochemical pathways. Utilizing single-nuclei RNAseq plus ATACseq multiomics, I have examined the development of RTT in human cerebral organoids from embryo to infant.

My graduate research contributions focused on the sodium-activated potassium channel Slick (Kcnt2) and its role in the peripheral nervous system. Chronic pain is associated with abnormal excitability of sensory dorsal root ganglion (DRG) neurons, resulting in persistent action potential firing and loss of firing accommodation. I identified Kcnt2 transcriptional activation is predominately regulated by inflammatory transcription factor NFκB. I discovered Slick channels were expressed in peptidergic nociceptors and packaged in large-dense core vesicles with calcitonin gene-related peptide (CGRP) for trafficking and localization to sites of injury and inflammation. Utilizing molecular, biochemical, electrophysiological and behavioral studies in a mouse model, I identified a significant physiological role for Slick channels in detection of thermal nociception and recovery of hyperalgesia during chronic neuropathic and inflammatory pain. These studies culminated in identifying a novel target for amelioration of chronic pain. In my time within the lab, I set up all pain model and behavioral studies that the lab continues to utilize, including sciatic nerve cuff chronic constriction for neuropathic pain, hindpaw formalin injection for inflammatory pain, and thermal and mechanical nociception behavioral testing.