Investigator, Instructor (M) Neurology, Mass General Research Institute

Instructor in Neurology Harvard Medical School

MD / PhD University of Illinois, Urbana-Champiagn 2015

BS Biochemistry Loyola University Chicago 2005

MS Chemistry Loyola University Chicago 2006

MS Physiology University of Illinois, Urbana-Champaign 2011

BA History Loyola University Chicago 2005

actin depolymerizing factors; actins; autism spectrum disorder; chemical biology; cytoskeletal proteins; epilepsy; extracellular matrix; mmp-9 My interest in the underlying physiology of epileptogenesis stretches back to my undergraduate studies and has more recently begun in earnest. Over the past few years I have applied multiple facets of an eclectic research background to identify and study new mechanisms of neuronal management of chloride, and ultimately GABA_A receptor (GABA_AR) reversal potential (E_GABA). I developed and employed multiple techniques, coded analysis routines, and provided for expression of a genetically encoded intracellular fluorescent chloride probe to demonstrate stable subcellular microdomains of chloride concentration and their relationship to EGABA (contribution 1), resulting in one of the “Top 10” articles of 2021 in the Journal of Neuroscience. In order to non-invasively measure extracellular chloride and understand whether chloride microdomains exist in the extracellular space I have employed skills ranging from synthetic chemistry to rodent surgery to develop a novel fluorescent chloride probe capable of truly non-invasive measurement of extracellular chloride both in vitro and in vivo. We have recently demonstrated that extracellular chloride is far lower than previously assumed and that low extracellular chloride values are similar when comparing mouse hippocampal slice cultures and intact mouse cortex (article 2, contribution 2). Extending this to a gyrencephalic traumatic brain injury swine model, we find that baseline extracellular chloride is similarly low but increases in the acute posttraumatic period to roughly match expected CSF levels (article 3, contribution 2). Understanding how this acute rise in extracellular chloride comes about, what effects it has on intracellular chloride and EGABA, and how it develops over chronic time periods in those piglets who go on to develop post-traumatic epilepsy versus those who do not will offer important insights into the mechanisms underlying epileptogenesis. This in turn will yield insights into how we might elucidate new treatment targets and strategies for refractory epilepsy, or even prevent the development of secondary epilepsies. The revelation that extracellular chloride is neither constant nor as high as previously assumed is a potentially paradigm-shifting development achieved by employing a model-independent experimental program focused on answering basic questions and letting the data define the model. My background in actin disassembly mechanisms prepared me well for epilepsy research, as it dealt with bridging a similar disconnect between the popularly-accepted model and recent observations. My approach was similar, asking questions about unresolved observations, making the unmeasurable measurable, and ultimately I found a vital function of an underappreciated protein (contribution 3). I will continue to apply these lessons to epileptogenesis.