Volume 11, Issue 1 | Winter 2026

Science Feature

Mitigating Microbial Metabolism of L-dopa to Enhance Treatment in Parkinson’s Disease

Since the early 1960s, levodopa (L-dopa) has been the gold standard for PD treatment. L-dopa, taken orally, is absorbed into the bloodstream, crosses the blood-brain barrier, and is converted to DA in the brain, thereby helping to alleviate the debilitating motor symptoms that are the hallmark of the disease. Unfortunately, use of L-dopa over the course of the disease (which may be years or even decades) leads to a loss of efficacy and the development of L-dopa-induced movement disorders (dyskinesias) or LID. Our research is focused on measures that may extend the useful lifetime of L-dopa therapy while reducing the risk of LID.

Recent studies have shown that Enterococcus faecalis, a ubiquitous member of the gut microbiome, metabolizes L-dopa to DA, with further conversion of DA to tyramine by another commensal species, Eggerthella lenta (Figure 1). Since DA produced systemically cannot cross the blood-brain barrier, these bacterial metabolic pathways effectively reduce L-dopa bioavailability. Genome-mining approaches revealed that E. faecalis expresses a highly conserved tyrosine decarboxylase (TyrDC) that is not inhibited by drugs commonly used to prevent the peripheral metabolism of L-dopa.

Figure 1. Gut microbial metabolism of L-dopa. L-dopa absorbed into the bloodstream crosses the blood-brain barrier (BBB) to increase dopamine in the brain. Gut metabolism by E. faecalis converts L-dopa to dopamine, effectively reducing the amount of L-dopa available for uptake.  Dopamine produced in the gut can be further metabolized to m-tyramine by E. lenta.

We are exploring two approaches to mitigate metabolism of L-dopa by the microbiome. In the first, we have used mitochondria-targeted drugs developed by the Kalyanaraman lab in collaboration with Micael Hardy (Aix-Marseille University) that have antimicrobial properties and transiently inhibit proliferation of E. faecalis, thus reducing metabolism of L-dopa over a period following treatment. In a mouse model, co-administration of selected MTDs with L-dopa increased DA in the brain [1]. In a second approach, in collaboration with the Kristich lab (MCW Department of Microbiology and Immunology), we have engineered a TyrDC knockout strain of E. faecalis that no longer metabolizes L-dopa. We are currently investigating the ability of this TyrDC knockout strain to displace indigenous E. faecalis in the gut and enhance L-dopa bioavailability. 

This research was supported in part by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, a program project formation award from the Advancing a Healthier Wisconsin Endowment, the International Research Project SuperO2 from CNRS (France), and the Harry R. and Angeline E. Quadracci Professor in Parkinson’s Research Endowment.

Reference

1. Cheng G, Hardy M, Hillard CJ, Feix JB, and Kalyanaraman B. (2024) Mitigating gut microbial degradation of levodopa and enhancing brain dopamine: Implications in Parkinson's disease, Commun Biol 7, 668.

Biophysics Mourns the Passing of W. Karol Subczynski, PhD, DSc

Karol was passionate about his research, and maintained many national and international collaborations. He was skilled in the saturation recovery EPR technique, often employing it in his studies. Karol was thoroughly engaged in manuscript writing, and published nearly 200 manuscripts and reviews during his career; his most recent article was published earlier this month. Karol’s role in the advancement of the science of cholesterol in membranes and its implications in cataract and other diseases, as well as the advancement of biological applications of high-field EPR spectroscopy, was huge.

We will miss Karol for his intellectual contributions, deep biophysical insights, warmth, and humanity.

Colleagues of Karol have shared some memories, which are available in the linked PDF.

Graduate Student Q&A

Learn about the students in our Biophysics Graduate Program.

Research Interests: My current research focuses on clinical applications of radio-pathomic maps in glioblastoma patients. Glioblastoma is an aggressive brain cancer with a dismal prognosis. The LaViolette lab has been studying it for over 10 years, and has developed a machine learning algorithm that generates radio-pathomic maps that identify areas of tumor beyond what is seen on MRI. My latest study tested the hypothesis that glioblastoma patients treated with tumor treating fields (TTFields) in addition to standard of care would have lower cell density and tumor probability within contrast enhancement and non-enhancing FLAIR hyperintensity segmentations compared with controls. We found that patients who used TTFields for at least 90 days with a 75% compliance rate had lower average cell density and tumor probability within these tumor segmentations compared with controls. We plan on supplementing these results with additional studies using corresponding histology. 

Future Plans: I plan to graduate in the coming year and work as a medical science liaison for a medical device company. I want to focus on clinical translation, bridging the gap between medical device companies and clinicians and researchers to ensure innovative technologies are being effectively implemented into patient care and research. 

Fun Fact: I've run the Chicago Marathon twice (2018, 2021) and most recently the Detroit Free Press International Half Marathon (from Detroit, Michigan, to Windsor, Canada, and back). I have also signed up for the Milwaukee Lakefront Half Marathon this coming October. Additionally, this is my third and final year as the Biophysics representative for the Graduate School Association. 

Biophysics Alumni: Where Are They Now?

Seminar Series

Our Spring 2026 Seminar Series takes place most Fridays throughout the semester, from 10 a.m. to 11 a.m., in MFRC 2063 (except as otherwise noted). For details, please visit the Biophysics Events page.

Department News

Farewell

• Callie Koenig (research technologist, Klug lab)
• W. Karol Subczynski (professor of biophysics)

Congratulations

• Jimmy Feix, Gang Cheng, and Balaraman Kalyanaraman published an article in Antioxidants.

• Alex Garces and Mike Lerch published an article in Journal of the American Chemical Society.

• Bryna Goeckner published an article in Human Brain Mapping.

• Julian Grosskopf successfully defended his PhD dissertation, titled "Advancing EPR methodology: experimental and computational innovations to study protein thermodynamics, kinetics, and conformations" (advisor: Michael T. Lerch, PhD).

• Julian Grosskopf was awarded the 2025 Friends of MCW Excellence in Research Award, which recognizes his current research accomplishments and future research potential.

• Carlos Herrada received the 2026 SoBLa Travel Award, supported by Montana Molecular, which will fund his travel to the 2026 Biophysical Annual Meeting in San Francisco. 

• Roger Johnson published an article in Trends in Pharmacological Sciences.

• Candice Klug was appointed interim executive vice chair in the Department of Biophysics.

• Candice Klug published an article in Communications Biology.

• Francesca Marassi published an editorial overview in Current Opinion in Structural Biology.

• Nikolai Mickevicius published a letter to the editor in Magnetic Resonance in Medicine.

• Kathleen Schmainda published an article in Scientific Data.

• Karol Subczynski published an article in Investigative Ophthalmology & Visual Science.

• Yaqiang Wang was awarded a one-year, $35,000 New Faculty Pilot Grant by the MCW Research Affairs Committee for his proposal, titled "Structural Basis of RNA Recognition by Small Molecules: Foundations for RNA-Targeted Therapeutics."

• Yaqiang Wang and Neha Ajjampore published an article in Nature Communications.

• Robert Wujek won a Best Podium Presentation Award at the Southeast Wisconsin Data Science (SEAWINDS) Collaborative's second annual SEAWINDS Research Symposium for his presentation, "iTB Maps: Using Convolutional Neural Networks with Multiparametric MRI to Visualize Infiltrating Brain Tumor.”
• Jacek Zielonka published an article in Chemical Research in Toxicology.
• Casey Zoss successfully defended his PhD dissertation, titled "Gallium maltolate for treatment of glioblastoma: cellular mechanisms and clinical biomarkers" (advisors: Kathleen M. Schmainda, PhD, and Christopher Chitambar, MD).

Biophysics Featured on NIH ORIP Home Page

Biophysics research based on the National Institute of Health Office of Research Infrastructure Programs-funded nuclear magnetic resonance spectrometer recently was highlighted by the NIH ORIP. The story features a recent study on the role of bacterial surface proteins in promoting extracellular vesicle secretion (Marassi lab), and also mentions our EPR S10 grants (PI: Klug) and recent efforts on large-scale molecular modeling (Marinelli lab).

Biophysics Faculty Received Outstanding Educator Awards

Congratulations to the Biophysics faculty who were awarded Graduate School Outstanding Educator Awards for the 2024–2025 academic year:

• Neil Hogg, PhD
• Candice S. Klug, PhD
• Michael T. Lerch, PhD
• Jason W. Sidabras, PhD

Featured Pet

Biophysics News is a quarterly MCW departmental newsletter aimed at enhancing departmental engagement through information and good news sharing. Do you have information you’d like to share—news, events, photos, a photo of your pet? Send it to Lydia.

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