Lab Members

Frances Jensen, MD, FACP

Education/Training

Smith College, Northampton, MA A.B. 1978 Psychology
Cornell University Medical College, NY, NY M.D. 1983 Medicine
Harvard University M.A. (Hon) 2007 Medicine

Personal Statement

The overall focus of the Jensen laboratory is to devise age-specific therapeutic strategies to prevent epilepsy and brain injury in perinatal period. We focus on understanding the molecular and cellular pathophysiology of 2 highly prevalent forms of injury: hypoxic encephalopathy and seizures in the full term infant and hypoxic/ischemic injury to the white matter (periventricular leukomalacia, PVL) in the premature infant. Our overall interest is on the interaction between brain development and injury. We have a specific interest in the role of glutamate receptor maturation in excitotoxicity and epileptogenesis in the immature brain. Finally, we also study the long term consequences of these processes on later life cognition and behavior.

Clinically, the seizure incidence in infancy is higher than at any other time in life, with the most common cause being lack of oxygen (hypoxia) and/or blood flow (ischemia), due to birth asphyxia, insufficient lung function, and infection, among other causes. Some infants go on to develop neurocognitive deficits, mental retardation, and/or epilepsy. In many cases, these newborn infants are refractory to conventional medications that are effective in older children and adults. The age-dependency and the lack of response to conventional medications suggest that this injury might have mechanisms different from those in a similarly affected mature brain. Our work thus far has identified a critical role of a specific neurotransmitter receptor, the AMPA subtype of glutamate receptors, in the vulnerability to and subsequent development of epilepsy. We have also shown that the presence of depolarizing GABA receptors and high levels of expression of the Cl cotransporter NKCC1 uniquely contribute to epilepsy in the developing brain. We use a combination of in vivo and in vitro models to perform translational studies. We are examining the sequence of changes that take place in the perinatal brain following an early life seizure, and how these can result in abnormalities of brain development and epilepsy. We currently have a Phase I/II study underway in human neonatal seizures based on our work (clinicaltrials.gov/ NCT00830531).

The second research emphasis is on injury to the premature brain. PVL is the major antecedent to cerebral palsy, and to date no specific treatment exists. PVL occurs in premature infants that have respiratory distress, hypotension, sepsis and other complication of prematurity. Given the improved medical techniques, the number of infants born between 25-27 weeks and less than 1500 grams in birthweight is rising, yet these infants are those with the greatest risk of such complications. We have used in vivo and in vitro rodent models of injury to the primary cell type in the white matter, the oligodendrocyte. We and collaborators have found that the immature forms of oligodendrocytes that are present in the premature brain appear to be more sensitive to hypoxia/ischemia than mature forms that are present in brains of individuals of older ages. We examined the mechanism of toxicity, and found that these cells transiently express glutamate receptors during the window of vulnerability to hypoxia/ischemia. Subsequent studies showed that pharmacologic blockade of glutamate receptors on oligodendrocytes prevented the PVL-like injury in rodent models. Further studies on human autopsy tissue have shown that these glutamate receptors are likely present in the human white matter brain during the window of vulnerability to PVL, increasing the clinical relevance of our findings in our animal models. These ongoing studies evaluating other mechanisms are designed to produce additional therapeutic strategies for this disease process.

Finally, a recent emphasis in the lab relates to cognitive consequences of epilepsy in the developing brain, but also at any age. Approximately 50% of people with epilepsy have cognitive or psychiatric deficits. We have shown that multiple pathways involved in activity-dependent synaptic plasticity and learning are also dysregulated by epileptic seizures. In the developing brain, this can interfere with normal critical period mechanisms, and result in abnormal networks. Certain pathways implicated in autism syndromes are affected by early life seizures, and indeed our animal models reveal autistic-like behavior and impaired critical period plasticity following early seizures. We also show that seizures can occlude normal Hebbian activity dependent mechanisms such as LTP and LTD. Other studies are identifying that homeostatic plasticity is also inhibited by seizures, enhancing epileptogenesis. These mechanistic studies are identifying potential intervention points to prevent the cognitive and behavioral consequences of epilepsy.

Marcus Handy

Education/Training

Temple University BA Biology

Personal Statement

As Lab Manager I ensure that our lab maintains compliance with all regulatory agencies at the Institutional (Penn IACUC and Penn/CHOP IRB) and governmental (NIH) levels, actively support the grant writing and submission process, procure lab supplies and equipment, and maintain a safe well organized environment for our lab members and visitors. Aside from administrative responsibilities I provide research support for studies apposite to epilepsy and age-specific therapeutic strategies to prevent epilepsy and brain injury in perinatal period.

Aaron Barbour, Ph.D.

Education/Training

Virginia Commonwealth University : Ph.D. Neuroscience 2020

Personal Statement

I received my PhD in neuroscience from Virginia Commonwealth University in 2020. My work in the Jensen lab focuses on how the mechanisms underlying neuronal hyperexcitability and seizures play a role in neurodegeneration and the progression of Alzheimer’s disease. To study these interactions, I utilize mouse models of Alzheimer’s disease and epilepsy and postmortem human brain tissue and image intact mouse brains with light sheet fluorescence microscopy to map seizure activation and pathological tau spread throughout the whole brain.

Bo Xing, MD, Ph.D.

Education/Training

Xi’an Jiaotong University, PhD 2010

Personal Statement

Dr. Bo Xing received his Ph.D. from Xi’an Jiaotong University, 2010. He did his postdoctoral training with Dr. Wen-Jun Gao at Drexel University from 2012-2018, and worked as research instructor from 2018 to 2019. Then He moved to UPenn and work with Dr. Frances E Jensen as Research Associate since 2020. His research interest is synaptic reorganization after early-life seizures.

Eunjoo Lancaster MD, Ph.D.

Education/Training

University of Maryland - Ph.D., Pharmacology

Korea University - MD, Medicine

Korea University - MS, Physiology

Sierra Dutko

Education/Training

Rowan University - BS, Biophysics

Keegan Hoag

Education/Training

Graduate of Haverford College, 2022 B.S. in Psychology and a minor in Economics.

Audrey Cavanah

Education/Training

UC Santa Cruz - BS, Molecular, Cellular, and Developmental Biology