Catherine Best-Popescu, PhD

Catherine Best-Popescu, PhD, is a research assistant professor in the Department of Bioengineering in The Grainger College of Engineering. Professor Best-Popescu’s research interests are in the area of disability and health.  She is specifically interested in the prevention of secondary impairments (e.g. psychosocial function) associated with disability to maximize quality of life and community participation among wheelchair users. A related interest is in examining education techniques to enhance functional mobility, prevent falls and secondary impairments, and effectively utilize assistive technology to promote health and well-being among individuals with disabilities.

Explain your research in neuroscience; what are you investigating? 
My lab, the Cellular Neuroscience Imaging (CNI) laboratory at Illinois, is currently investigating neuronal repair, and neurodegenerative mechanisms following impact-induced injury. We develop and analyze therapies in cellular and mouse models of brain injury in parallel with studies of patients with Traumatic Brain Injury (TBI). We use a fluid percussion device, which is essentially a weighted hammer attached to a pendulum. Once released, the hammer hits a volume of fluid which generates a pressure wave that supplies a controlled and measurable impact to both cells and mice. Currently, we are studying the ability of anti-inflammatory Omega-3 fatty acids such as Docosahexanoic acid (DHA), and the DHA endocannabinoid-like metabolite N-docosahexanoylethanolamine (DHEA, also known as synaptamide) and cooling, to provide protection against impact-induced trauma. We measure neuronal recovery, and we quantify trauma-induced cellular and whole brain alterations using standard immunohistochemistry and novel label free imaging techniques. We use spatial light interference microscopy (SLIM), a quantitative form of microscopy, to characterize and map changes in global brain structure and cellular morphology following injury. The goal for us, is to understand TBI pathophysiology across the scales: from cells, to the whole brain, and on through to effects on function and behavior. Our key translational themes involve neuroprotection through photobiomodulation and anti-inflammatory Omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment. We have partnered with physicians at the Lovell Federal Health Care Center (Chicago), to test the effects of ultraviolet light (UVB) on sleep, mood, cognition, behavior, and disease symptomology in veterans with TBI. This study follows preliminary findings from a pilot human study that showed promising beneficial immunomodulatory effects of UVB light conducted here at Illinois.

How are you currently conducting your research?
I have three graduate students, Jorge Maldonado and Young Jae Lee from the Neuroscience Program, and Edward Chen from the Bioengineering department, and a number of multidisciplinary undergraduate students working on a number of related basic science research and brain imaging projects. In order to image cellular changes across the whole brain following injury we use clarity and expansion microscopy (ExM), two chemical techniques that essentially remove lipids (fats), and physically expand tissue, and in our case mouse brains, in 3D 4- 10x, respectively. These techniques allow us to probe trauma-induced changes, and treatment effectiveness, approaching the single molecule level within the context of the whole brain.

How does being part of the broader Illinois research community support and enhance your work?
I have benefitted immensely from the vibrant and diverse collaborative research community here at Illinois. My research and teaching philosophy has followed closely the sentiment and advice of Nobel laureate Santiago Ramon y Cajal, one of the seminal figures of neurobiology. Cajal emphasized the need for breadth of knowledge in educating scientists. In 1916, in his Advice for a young investigator he wrote, "the biologist does not limit his studies to anatomy and physiology, but also grasps the fundamentals of psychology, physics, and chemistry." Currently, we are working with Karen Doty, from Veterinary Medicine; Gabriel Popescu from Electrical and Computer Engineering; Paul Selvin from Physics; and Paul Braun from the Materials Science and Engineering department—all experts in their respective fields. Together, we tackle complex scientific problems, each bringing our own perspective, insight, and toolbox to the table. My students and I benefit immensely from their expertise, guidance, and shared resources.

In what ways do you envision your work improving society or reaching people?
Traumatic brain injury (TBI) is a leading cause of death and disability in children and young adults, and TBI accounts for 50,000 deaths in the U.S. each year. Every eight seconds, someone in this country sustains a TBI due to a fall, a sports-related injury, an automobile collision or an accident; and TBI is the signature injury of our veterans today. Currently, there is no specific treatment for the neurological sequelae of TBI. TBI therapy is confined to reduction of intracranial pressure and management of physiological homeostasis. My lab’s approach may lead to an improved understanding of mechanisms of secondary injury, the biochemical derangements, that occur following the initial traumatic event and that are thought to be responsible for the varied and unpredictable, chronic cognitive, neuropsychiatric and executive deficits that occur following TBI. Both UVB photobiomodulation and n-3 PUFA treatment are non-invasive, safe, non-pharmacological, and have a wide range of neuroprotective and anti-inflammatory benefits that represent promising TBI treatment lines worthy of further investigation.

Do you have a personal story or path that led to your interest in this particular area of research?
When I graduated from UMASS with a BS in Biology and Psychology, I wanted to do ‘significant medical research.’ The jobs I was applying for required American Society for Clinical Pathology certification (ASCP), so I enrolled at Northeastern University—one of two places in the U.S. that had an ASCP certification program. I got a job as a research observer in an Alzheimer’s study testing the Simulated Presence Theory. One day after work, I hurried to the Coop in Harvard Square to buy a copy of Science & Medicine to read an article linking Apo E and increased risk for developing late onset Alzheimer’s disease. In my haste, I inadvertently picked up the previous issue. On my train ride home, irritated at what I thought was a wasted trip, I flipped through the articles anyway, and to my surprise, I found an exciting article entitled The fish oil puzzle by Scott Goodnight that chronicled the discovery that omega-3 polyunsaturated fatty acids (n-3 PUFA) have beneficial effects on cardiovascular mortality. The article laid out epidemiologic evidence linking cold water fish diets, rich in n-3 PUFA, to a reduced risk for cardiovascular disease, described myocardial infarction prevention following n-3 PUFA treatment in a dog model, and outlined the effects of toxins on the synchronized beating of heart cells taken from neonatal mice. The described research designs were elegant and seemed to follow a clear logical progression of hypothesis testing that were rewarding all on their own. The results of the studies were both fascinating and inspiring. That night I thought, that’s exactly the type of methodical translational research I want to do, and if I ever get there I’ll have truly succeeded!

As a part of the ASCP certification program at Northeastern, I took a Medical Laboratory Sciences class taught by Dr. Mike Laposata. Following the class, Dr. Laposata encouraged me to pursue my PhD, something I had never even considered. Later that year, I started conducting my doctoral research in his laboratory in the Pathology Department at Massachusetts General Hospital. We were investigating the pathophysiology of alcohol abuse, and fatty acid abnormalities in different disease states such as pediatric bipolar disorder, cystic fibrosis and Multiple Sclerosis (MS). One evening while working in the lab, Dr. Laposata's office door flew open, as it often did, and we all leapt to attention, as we did, and he said, “Catherine, how would you like to work with Dr. Leaf on a study testing the antiarrhythmia effects of omega-3 fatty acids in a human study?” I jumped at the opportunity. To my surprise, when I reviewed Dr. Leaf’s research I discovered that the article that had inspired me, by Scott Goodnight, had largely outlined Dr. Leaf's research. As I watched PUFA-treated synchronous heart cells beating in a petri dish in Dr. Leaf’s laboratory, and as I tried to calibrate his Gas Chromatography-Flame Ionization Detector (GC-FID) for use in his evaluation of n-3 PUFA as a prevention therapy of secondary MI’s in a human clinical trial, I felt the reward of research progress.

In my own work, I was studying the biochemical and biophysical properties of fatty acid ethyl esters (FAEE). FAEE are non-oxidative metabolites of alcohol. Given the time scale for alcohol-induced tolerance, I chose to use red blood cells (RBCs) as a model for neuronal membranes. I looked at FAEE speciation in RBCs taken from normal controls, and from alcoholics. I compared normal RBC morphology to RBCs taken from alcoholics in the emergency room, and from acutely intoxicated healthy drinkers. I observed changes in RBC membrane (ghosts) properties with a scanning electron microscope--they appeared more rigid. This was an exciting finding at the time, because elastic RBCs survive circulation through the spleen and microvasculature. While rigid RBCs would break unable to traverse the narrow channels, and this could serve as a mechanism for alcoholic anemia. I hypothesized that FAEE insert in the RBC membrane, and following chronic alcohol use, they accumulate over time and become trapped within the hydrophobic core of lipid membranes. Once stuck within the membrane, the FAEE could explain the alcohol-induced RBC rigidity we observed. Luckily for me, MGH has interdisciplinary research seminars, and I attended a talk discussing lipid rafts, protein trafficking, and disease. It closed with a single movie of a RBC flickering. The movie was taken with a new form of microscopy–Hilbert Phase Microscopy (HPM). HPM is a non-invasive, label-free method for quantifying altered membrane dynamics. I contacted the referenced post-doctoral researcher, Gabriel Popescu, and asked if we could collaborate to quantify the elasticity and rigidity of red blood cells following FAEE exposure. The subsequent collaboration led to the successful completion of my PhD thesis, many successful publications, and my marriage to Gabriel Popescu.

As a visiting research scientist at Harvard in the School of Engineering and Applied Sciences, I continued to quantify RBC membrane stiffness by measuring RBC deformity profiles during flow through microchannels of various confirmations, and I learned numerous molecular biology techniques in Dr. Bonventre’s lab, in the Department of Medicine, at Brigham and Women’s Hospital as a post-doctoral research fellow. When I left Boston, I described myself as a lipid biochemist. Upon arrival at Illinois, Gabi went on to further develop his quantitative microscopy techniques and I got a job teaching Medical Neuroscience in the College of Medicine. I felt very fortunate, as Neuroscience is by far the most interesting subject to study and teach! Today, as a research professor in the Bioengineering department, I continue to study the beneficial effects of n-3 PUFA, to utilize novel imaging techniques to quantify changes in cells and tissue, and I continue to work at the interface of basic and clinical research as we start to investigate the effects of UVB photobiomodulation treatment in individuals with TBI.