Volume 9, Issue 1 | Winter 2024

Science Feature

Funding received for studies on neuroprotective mechanisms of tetrahydrobiopterin in hypoxia-ischemia fetal brain injury and motor impairments

By Jeannette Vasquez Vivar, PhD

My collaborators and I were recently awarded R01NS130258 by the National Institute of Neurological Disorders. This research project, which is part of our larger research program, focuses on the role of redox-active small molecules as possible fetal brain neuroprotectants and mechanisms of neuronal cell death caused by the failure to cope with oxidant injury. Specifically, the new project will study the role of tetrahydrobiopterin in one form of non-apoptotic cell death that is etiologically linked to oxidants.

We have shown that tetrahydrobiopterin, a cofactor for neurotransmitter synthetic enzymes in the brain, is significant for developing motor deficits following antenatal (fetal) hypoxia-ischemia injury. Tetrahydrobiopterin plays a crucial role in reperfusion-reoxygenation injury—which is predictive of motor deficits on MRI—by regulating superoxide-mediated injury. Notably, congenital tetrahydrobiopterin deficiencies from mutations in any of the enzymes involved in the biosynthesis and recycling of tetrahydrobiopterin (such as mutation R150G in the SPR gene) all result in motor deficits in children. To advance our preclinical studies, we have generated rabbit SPR-KO and SPR-R150G knock-in models to investigate whether neuronal cell death by specific pathways of oxidative stress related to tetrahydrobiopterin in the fetal brain determines the development of infancy motor deficits, as seen in human cerebral palsy. The overall goal of this project is to map together possible pathways to establish the most significant mechanisms of oxidant injury to brain loss of function; this will render critical information to define better therapies for fetal brain hypoxia-ischemia injury.

Our multiple-PI project is the product of the intersection of collaborators with expertise in neonatology and movement disorders (Dr. Sidhartha Tan, Wayne State University); application of CRISPR-CAS technology in large animal models (Dr. Jie Xu, University of Michigan); and tetrahydrobiopterin/nitric oxide synthase, free radicals, and electron paramagnetic resonance (Dr. Jeannette Vasquez Vivar).

Graduate Student Q&A

Learn about the students in our Biophysics Graduate Program.

Savannah Duenweg

Program: Biophysics
Mentor: Peter LaViolette, PhD
Year Entered MCW: 2020

Background: After graduating from Pembine High School in 2016, I made the trip to Milwaukee to pursue my undergraduate education.

I graduated from the Milwaukee School of Engineering in 2020 with a BS in biomedical engineering and a minor in user experience. I started in Dr. LaViolette’s lab late August 2020 as a direct entry into the biophysics program and immediately started working on our prostate cancer radio-pathomics studies. After spending nearly my first year virtually, I couldn't have asked for a better environment in our lab and have had a ton of fun working in the LaViolette lab.

Research Interests: I am passionate about the field of cancer imaging research. Currently, I am primarily focused on comparing prostate cancer MRI to histological signatures of tumors and assessing their patient prognostic implications. I also jump in on small projects with the LaViolette lab brain bank to evaluate radio-pathomic relationships in glioblastoma patients.

Future Plans: My plan is to continue to publish findings from my dissertation and establish myself as an expert in cancer imaging. After completing my degree, I plan to pursue a career as a research scientist to continue to develop myself under an established mentor in my field. I additionally envision myself branching out into other cancer imaging subgroups.

Fun Fact: I am a dog mom to two little gremlins, Jasper and Lyric. I am also an avid reader and read 52 books (almost 23,000 pages) last year!

Biophysics Alumni: Where Are They Now?

Candice S. Klug, PhD

Title: James S. Hyde Professor of Biophysics; Director, National Biomedical EPR Center; Program Director, Biophysics Graduate Program; Director, Interdisciplinary Program (IDP) in Biomedical Sciences; MCW
Year Graduated MCW: 1999
Mentor: Jimmy B. Feix, PhD

Katie M. Schultz, PhD

Title: Research Scientist I, Department of Biophysics, MCW
Year Graduated MCW: 2011
Mentor: Candice S. Klug, PhD

Eric Paulson, PhD

Title: Professor and Chief Physicist, Department of Radiation Oncology; Professor, Departments of Radiology, Biophysics, & Biomedical Engineering; MCW
Year Graduated MCW: 2008
Mentor: Kathleen M. Schmainda, PhD

Andrew S. Nencka, PhD

Title: Associate Professor, Department of Radiology; Director of Operations, Center for Imaging Research; MCW
Year Graduated MCW: 2009
Mentor: Daniel B. Rowe, PhD

Peter S. LaViolette, PhD, MS

Title: Robert C. Olson, MD Professor of Radiology; Director, Radiology Quantitative Imaging Laboratory; Director, MCW Cancer Center Translational Metabolomics Shared Resource; MCW
Year Graduated MCW: 2011
Mentor: Kathleen M. Schmainda, PhD

Nikolai J. Mickevicius, PhD

Title: Assistant Professor, Department of Biophysics, MCW
Year Graduated MCW: 2018
Mentor: Eric Paulson, PhD

Department News

Congratulations

Mona Al-Gizawiy was awarded two $50,000 one-year grants from Advancing a Healthier Wisconsin ("Characterization of response to gallium maltolate in treatment-resistant glioblastoma" & "Developing a novel gallium compound for the treatment of metastatic breast cancer") as well as an MCW Center for Imaging Research Intramural Pilot Award ("Targeting treatment-resistant glioblastoma via iron-dependent and -independent means") funded by the Daniel M. Soref Charitable Trust.
Mona Al-Gizawiy, Robert Wujek, Melissa Prah, & Kathleen Schmainda published an article in Frontiers in Oncology.
Savannah Duenweg published an article in Laboratory Investigation.
Balaraman Kalyanaraman published an article in Cancer Communications.
Nikolai Mickevicius published an article in Journal of Magnetic Resonance.
Melissa Prah & Kathleen Schmainda published an article in Frontiers in Oncology.
Kathleen Schmainda published an article in Journal of Neurosurgery Case Lessons.
Gopinath Tata, Kyungsoo Shin, & Francesca Marassi published an article in Journal of Structural Biology.
Jeannette Vasquez Vivar and collaborators were awarded a multiple-PI R01 by the NINDS, titled "Ferroptosis in Knock-In Sepiapterin Reductase Mutation Rabbits."
Jacek Zielonka published an article in Redox Biology
Jacek Zielonka and Aleksandra Grzelakowska published an article in Free Radical Biology and Medicine.

Mona Al-Gizawiy celebrating receipt of her AHW grants with the Schmainda lab (pictured from left to right: Jaimy Pettit, Melissa Prah, Casey Zoss, Mona Al-Gizawiy, & Kathleen Schmainda).

United Way Snack Pack Drive a Success

Many thanks to everyone in Biophysics who helped us exceed our goal for the United Way Snack Pack Drive! We collected enough for 106 packs, each with eight healthy snacks.

This was a great way to kick off the holiday season by helping others.

Special thanks to Laura Borst for organizing the drive, and for making the snack packs extra special with fun, inspirational messages.

Thanks also to Shannon Gustavson for helping Laura assemble the snack packs.

Graduate School Research Poster Session

Some of our Biophysics graduate students presented posters at the 33rd Annual School of Graduate Studies & Office of Postdoctoral Education Research Poster Session on Dec. 5, 2023. This poster session offers trainees the opportunity to celebrate their scientific progress and accomplishment with the MCW community. Good work, all of you!

Seminar Series

Our spring 2024 Biophysics Seminar Series takes place most Fridays throughout the semester, from 10 a.m. to 11 a.m., in the Biophysics conference room MFRC 2063 (except as otherwise noted). For details, please visit the Biophysics Events page.

Jan. 26 | Ilirian Dhimitruka, PhD (University of Wisconsin - Parkside)
Synthesis and EPR spectroscopy applications of CTR (crowded trityl radicals) that reports simultaneously on acidity and oxygenation in animal models

Feb. 2 | Emily S. Finn, PhD (Dartmouth College) [Zoom only]
Idiosynchrony: Using naturalistic stimuli to draw out individual differences in brain and behavior

Feb. 9 | Stephen Mazurchuk (MCW)
An embodiment account of category related semantic deficits

Feb. 16 | Patrick Brennan (MCW)
Defining the conformational landscape governing ligand mediated B2AR signal transduction

Feb. 23 | Ross Collery (MCW)
Using the zebrafish eye as a window to study consequences of retinal disease

March 1 | Vasileios Petrou, PhD (Rutgers New Jersey Medical School)
Investigating the structural basis of polymyxin resistance using cryo-electron microscopy

March 8 | Jacek Zielonka, PhD, DSc (MCW)
Novel tools for modulation and detection of cellular oxidants

March 15 | Akansha Sharma, PhD (MCW)
Optical characterization of materials using THz time domain spectroscopy

March 22 | Lan Zhu, PhD (MCW)
Illuminating the molecular mechanisms of G protein-coupled receptors: Insights from cryo-EM and X-ray perspectives

April 12 | L. Tugan Muftuler, PhD (MCW)
Advancing MRI methods and deep learning tools to study low back pain

April 19 | Michael T. Lerch, PhD (MCW)
EPR studies of signaling selectivity in the β2 adrenergic receptor

April 26 | Jan K. Rainey, PhD (Dalhousie University)
Untangling molecular-level and nanoscale contributions to spider silk mechanics

May 3 | Kathleen P. Howard, PhD (Swarthmore College)
Probing the conformation and dynamics of membrane-bound influenza A M2 protein using SDSL-EPR

Pet of the Month

Pet Name: Merle
Age: 8 years
Likes: Naps, snacks, and sunbathing
Dislikes: Most forms of weather
Guardian: Lydia Washechek

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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