Volume 11, Issue 2 | Spring 2026

Science Feature

Developing EPR Technology to Capture Protein Dynamics Across Timescales

Site-directed spin labeling (SDSL) combined with electron paramagnetic resonance (EPR) spectroscopy is a powerful approach for measuring protein dynamics. In SDSL, stable paramagnetic probes are introduced at specific sites within a protein, enabling EPR to detect local structural changes and motions. A key strength of this approach is its ability to probe systems that are difficult for other techniques, including large protein complexes and membrane proteins, under physiologically relevant conditions.

SDSL-EPR can access dynamics spanning an exceptionally broad range—from rapid backbone fluctuations on picosecond to nanosecond timescales to slower processes such as protein folding, conformational exchange, and complex formation occurring over microseconds to seconds [1]. We recently published technological advances that significantly expand its capabilities in the biologically critical millisecond regime: a complete high-pressure EPR system that uses rapid pressure jumps to perturb protein equilibria and measure relaxation kinetics [2], as well as a high-sensitivity stopped-flow EPR system that monitor structural changes following rapid mixing [3].

Our integrated stopped-flow EPR system comprises a custom resonator housing and stopped-flow mixer assembly, as well as a novel dielectric X-band resonator and sample tube designed and constructed in collaboration with Profs. Candice Klug and Jason Sidabras. This design achieves the lowest sample consumption reported for any stopped-flow EPR system, extending the applicability of stopped-flow EPR to exploration of conformational dynamics that drive protein-protein and protein-ligand interactions in complex, biomedically relevant proteins.

We also published the first pressure-jump EPR system of any kind. Because different protein conformations generally have different volumes, the application of pressure modulates equilibrium populations toward the conformation with the smallest volume. Together with variable-pressure continuous-wave EPR and pressure-resolved double electron-electron resonance methods we pioneered, high-pressure SDSL-EPR can now be utilized to explore equilibrium structure and dynamics as well as millisecond-timescale kinetics in biomedically relevant proteins.

References

1. Brennan PC, Grosskopf JD, Garces AM, Trier CL, Lerch MT. Capturing protein dynamics across timescales with site-directed spin labeling electron paramagnetic resonance spectroscopy. Curr Opin Struct Biol. 2025 Aug;93:103073.
2. Grosskopf JD, Sidabras JW, Altenbach C, Anderson JR, Mett RR, Strangeway RA, Hyde JS, Hubbell WL, Lerch MT. A pressure-jump EPR system to monitor millisecond conformational exchange rates of spin-labeled proteins. Protein Sci. 2024 Dec;33(12):e5220.
3. Garces AM, Mett RR, Klug CS, Sidabras JW, Lerch MT. A high-sensitivity stopped-flow EPR system to monitor millisecond conformational kinetics in spin-labeled proteins. Protein Sci. 2025 Aug;34(8):e70214. 

Biophysics Presents

3rd Annual James S. Hyde, PhD, Memorial Lecture

Graduate Student Q&A

Learn about the students in our Biophysics Graduate Program.

Research Interests: My doctoral work focuses on the integration of quantitative MRI into radiation therapy planning. What I hope to do is create a pipeline for physicians to evaluate the tumor microenvironment on a regular basis during treatment, so that they can adapt the dose being delivered to improve patient outcomes.

Future Plans: My interests dovetail with the practice and philosophy of radiation oncology quite nicely. I will be returning to medical school in January 2027, where I intend to spend as much time as possible exploring that field. Eventually I want to blend clinical practice and scientific research via clinical trial development.

Biophysics Alumni: Where Are They Now?

Department News

Welcome

• Anshul Chaudhary (research scientist, Marassi lab)
• Aashraya Iyer (graduate student, Leone lab)
• Mrina Mtenga (ACS post baccalaureate fellow, Marinelli lab)
• Jack Russo (graduate student, Klug lab)
• Garret Wang (graduate student, Binder lab)

Farewell

• Swapna Bera, PhD (postdoctoral researcher, Marassi lab)

Congratulations

• Mona Al-Gizawiy was awarded a five-year, $2.97 million R01CACA299189, titled "Gallium maltolate for the treatment of difficult-to-treat high-grade pediatric brain tumors," by the National Cancer Institute. 
• Patrick Brennan successfully defended his PhD dissertation, titled "On the Molecular Mechanisms Underlying β2-Adrenergic Receptor Activation" (advisor: Michael T. Lerch, PhD).
• Bryna D. Goeckner successfully defended her PhD dissertation, titled "A Multimodal Study of Concussion, Contact Sport Exposure, and Hormonal Factors in Female Athletes" (advisor: Timothy B. Meier, PhD).
• Kyle Johnson & Jason Sidabras published a technical note in Magnetic Resonance in Medicine.
• Matea Juric & Jacek Zielonka published an article in Journal of Experimental & Clinical Cancer Research.
• Balaraman Kalyanaraman gave a presentation at the WPA Annual Parkinson's Symposium in April 2026.
• Balaraman Kalyanaraman & Gang Cheng are inventors of US Patent 12,594,283, "Mitochondria-Targeted Atovaquone: A More Potent and More Effective Antitumor, Antimicrobial, and Antimalarial Drug," which was issued April 7, 2026.
• Candice Klug was featured by MCW Stories.
• Richard Mett, Anand Anilkumar, Alex Garces, Mike Lerch, Candice Klug, & Jason Sidabras published an article in Review of Scientific Instruments.
• Nikolai Mickevicius published an article in Magnetic Resonance Imaging.
• Kathleen Schmainda published an article in Scientific Data and a book chapter in Quantitative Imaging in Medicine Applications and Clinical Translation.
• Yaqiang Wang was awarded a three-year, $231,000 Career Development Award, titled "Structural Basis of CUG-Repeat Recognition by Muscleblind-like Proteins in Myotonic Dystrophy–Associated Cardiomyopathy," from the American Heart Association.
• Nick Wood published an invited commentary in mSphere.

Pictured above: Vanessa Leone and Carlos Herrada at the IDP recruitment booth at the Annual Biophysical Society Meeting (Feb. 20–25, 2026).

Pictured above: Mona Al-Gizawiy celebrating receipt of her R01.

Pictured above: Yaqiang Wang celebrating receipt of his Research Affairs Committee and American Heart Association awards.

Pictured above: Bryna Goeckner celebrating her successful dissertation defense.

Pictured above: Mike Lerch and Patrick Brennan celebrating Patrick's successful dissertation defense.

Years of Service

These Biophysics employees were honored for their years of service to MCW. Thank you for your hard work and dedication!

• Nick Cina, PhD (postdoctoral researcher, Klug lab) - 5 years
• Katie Schultz, PhD (research scientist, Klug lab) - 20 years
• Lydia Washechek (grants operations coordinator sr) - 10 years

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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