Research Lab Bench



In the Department of Biophysics, scientists use physical science methods to study biological systems. Specifically, our research is focused in the areas of EPR, MR physics and brain imaging, and redox research.

Test tubes in circular drum

EPR Research

The Department of Biophysics is home to the National Biomedical EPR Center, which is the most extensive electron paramagnetic resonance (EPR) facility in the nation. Research conducted within the EPR Center includes technological innovation and application of new techniques to biological problems. The main focus areas are spin labeling of proteins and lipids, structural and conformational changes of proteins, redox changes at the active site of metallo-proteins, and oxidants and free radical formation in tumorigenesis and tumor progression and in drug resistance in cancer. The EPR Center houses an array of internally developed and commercial EPR instrumentation, a specialized engineering/development staff capable of steadily and significantly advancing the state-of-the-art technology for biomedical applications of EPR spectroscopy, and a scientific staff with broad expertise.

Brain image on monitor close up

MR Physics & Brain Imaging Research

Scientists in the Department of Biophysics have been engaged in magnetic resonance (MR) research for more than 25 years, beginning with the installation of one of the first 1.5 Tesla scanners produced by GE Healthcare. Early papers were concerned mostly with the development of surface coils tailored to nearly every body part in the context of musculoskeletal radiology. MCW students and faculty published the first paper on functional MRI (fMRI) in 1992 and on resting-state fMRI in 1995. Technology development continued to be important, including the introduction of the local gradient coil for fMRI and development of the widely used fMRI software program AFNI (Analysis of Functional NeuroImages). Currently, emphasis on fMRI technology continues, but, increasingly, MRI research in the Department of Biophysics involves mechanisms of fMRI contrast in the brain and applications of fMRI to neurological and psychiatric disorders (e.g., early disease detection, precision disease prevention, prediction of disease development, and assessment of treatment efficacy in Alzheimer’s disease research). Strong interdisciplinary collaborations exist, centering on chronic pain mechanisms, psychiatric depression, and other fields in neuroscience.

Hand studying trend chart

Redox Research

Scientists in the Department of Biophysics are internationally recognized for their expertise and contribution to the field of free radical and redox biology. The main research focus is on establishing the role of free radicals and oxidants in pathophysiological conditions (e.g., in cardiovascular diseases, neurodegeneration, and cancer) and in normal cell function. The department provides an environment conducive to the development of novel, rigorous chemical probes and assays for monitoring the generation of free radicals in cells (in vitro) and in animals (in vivo). These include fluorogenic and bioluminescent probes, EPR spin traps, and probe-free assays (e.g., redox immunoblotting [peroxiredoxins, thioredoxins] and low-temperature EPR studies of the redox status of cellular protein metal centers). Ongoing collaborative work within MCW (e.g., Cardiovascular Center, Cancer Center) and with other institutions utilizes these assays to understand the role of oxidants in cardiovascular diseases (e.g., stroke, ischemia-reperfusion), neurodegeneration (e.g., Parkinson Disease), and cancer (e.g., cancer cell proliferation, chemoprevention, and chemotherapy).


Free Radical Research Center

Free Radical Research Center

The purpose of the Free Radical Research Center (FRRC) is to promote and stimulate free radical research at MCW, to help acquire increased NIH and other extramural funding for MCW researchers engaged in free radical and nitric-oxide-related research, and to promote increased collaborations in free radical research between basic scientists and clinical researchers. The FRRC provides an environment for the development of new, rigorous probes and assays for free radicals (e.g., superoxide and nitrogen dioxide) and non-radical oxidants (e.g., hydrogen peroxide, peroxynitrite, hypochlorous acid). The users of FRRC have access to various bioanalytical instrumentation, including high performance chromatography with absorption, fluorescence, electrochemical and mass spectrometric detection, fluorescence spectrometer and microscope, multimode plate reader, spectrophotometer, equipment for redox immunoblotting, as well as stopped flow system for investigation of rapid chemical and enzymatic reactions. 
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National Biomedical EPR Center

National Biomedical EPR Center

The National Biomedical EPR Center was established in 1976 as a biotechnology resource center to enhance biomedical research use of EPR. The EPR Center at MCW is one of the largest EPR facilities in the nation and was supported by an NIH P41 research resource award from 1976 to 2019. Research at the National Biomedical EPR Center continues to be technologically innovative and applies new techniques to biological problems. The EPR Center houses S-, X-, L-, Q- , and W-band EPR spectrometers, many with DEER, ENDOR, ELDOR, saturation-transfer, saturation-recovery, and multiquantum capabilities. 
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Redox & Bioenergetics Shared Resource

Redox & Bioenergetics Shared Resource

The MCW Cancer Center Redox & Bioenergetics Shared Resource is dedicated to cancer research through the utilization of cutting-edge technology to advance the field of cancer redox and bioenergetic function. The resource focuses on using in vitro, ex vivo and in vivo techniques to determine the redox and bioenergetic status of cancer cells, to develop new drugs and approaches in chemoprevention and cancer cell treatment. The users of the Resource have access to state-of-the art instrumentation, including Seahorse XF96 extracellular flux analyzer and Shimadzu LC-MS/MS systems, dedicated to the analyses of cellular redox and bioenergetic function. In addition, the resources provided by the Free Radical Research Center are available to the users of the Redox & Bioenergetics Shared Resource.
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Redox Biology Program

Redox Biology Program

The mission of the Redox Biology Program is to foster communication and an exchange of expertise among a broad, interdisciplinary group of clinicians and basic science researchers in the spirit of collaborative research.
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Other Centers


Our faculty are supported by internal and external funding sources, including the National Institutes of Health.

R01 CA221938

MPI: Christopher Quarles / Kathleen Schmainda / Jerrold Boxerman / Leland  Hu
Multi-Site Validation and Application of a Consensus DSC MRI Protocol
The overall goal of this multi-site clinical trial is to validate and demonstrate the clinical utility of a standardized protocol for imaging brain tumor perfusion. Such validation will help to promote widespread adoption of the consensus protocol, thereby improving the reliability of perfusion imaging for response assessment of brain tumor patients in routine neuro-oncology practice and prospective clinical trials.

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R01 AA022986
MPI: Narayan Avadhani / Balaraman Kalyanaraman
CYP2E1 Mediated Mitochondrial Injury and Cell Damage in Alcohol Liver Disease
A major objective is to investigate the mechanisms of alcohol induced mitochondrial dysfunction and develop antioxidants and enzyme inhibitors to minimize alcohol induced liver damage.

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R01 CA208648
MPI: Ming You / Balaraman Kalyanaraman
Chemoprevention of Lung Cancer with Mitochondria-Targeted Honokiol
We will evaluate the chemopreventive potential of Mito-HNK, a mitochondria-targeted compound, using both in vitro and in vivo models of lung adenocarcinoma (LUAD) and determine its mechanism of action, to determine its efficacy for inhibiting LUAD progression and metastasis and its suitability for human clinical trials.

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R01 EY015526
PI: W. Karol Subczynski
Lipid Domains in Lens Membranes of a Single Eye: EPR Spin-Labeling Studies
The long-term objective of this proposal is to achieve a greater understanding of the function of cholesterol in fiber cell membranes.

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R01 GM108817
PI: Candice Klug
09/01/14–05/31/19 (NCE)
LptA-Mediated Transport of LPS
The proposed studies focus on how the periplasmic protein LptA receives LPS from the IM-associated protein LptC, how LptA protects the hydrophobic acyl chains of LPS as it crosses the periplasm, and how LptA delivers LPS to LptDE at the OM. Genetic screenings, laser light scattering analyses, EPR spectroscopy studies, and isothermal titration calorimetry (ITC) measurements will provide detailed insights into the mechanism of LPS transport across the periplasm of Gram-negative bacteria.

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R01 GM114234
PI: Jimmy Feix
04/01/15–03/31/20 (NCE)
Mechanism of Activation and Membrane Interactions of Pseudomonas Toxin ExoU
In this project biochemical and biophysical studies will be used to elucidate the molecular mechanism of activation for the phospholipase ExoU, with a long term goal of facilitating the development of novel inhibitors to reduce tissue damage or sepsis due to P. aeruginosa infection.

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R01 NS081936
MPI: Sidhartha Tan / Jeannette Vasquez Vivar
8/15/13–6/30/19 (NCE)
Tetrahydrobiopterin in Fetal Hypoxia Brain Injury
The major goals of this project are to investigate mechanisms of neuronal dysfunction associated with loss of BH4 in antenatal hypoxia-ischemia (HI) at a premature gestation. Using surrogate markers of magnetic resonance imaging this proposal, will study neuronal cell responses in the early critical phase of injury, which seems to determine the eventual course of events leading to movement disorders of cerebral palsy.

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R13 HL146109
PI: Neil Hogg
2019 Nitric Oxide Gordon Research Conference and Seminar: Gasotransmitters in Harmony
The 2019 Nitric Oxide GRC/GRS “Gasotransmitters in Harmony” will bring together scientists from all over the world to discuss the importance of Nitric Oxide and other gasotransmitters. These molecules play a critical role in proper cardiovascular and pulmonary function and work together to maintain these systems in a healthy state. This is an exciting and novel direction for this conference, which will aim to provide networking opportunities for young, female, and underrepresented scientists to enhance their career trajectories.

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R21 AG056882
PI: Shi-Jiang Li
Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development
The overall goal of this project is to determine whether, during the preclinical Alzheimer’s disease developmental phase in CN older subjects with the apolipoprotein ε4 allele, decreased abnormal hyperfunctional connectivity can be correlated with improved episodic memory using a perturbation, such as a low dose of levetiracetam.

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R25 HL125260
MPI: Dawn Bragg / Jeannette Vasquez Vivar
Diversity Summer Health Research Education Program
Undergraduate Training grant to increase the diversity force in medical research.

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U01 CA178960
MPI: Michael Dwinell / Balaraman Kalyanaraman
Targeting Pancreatic Cancer Energy Metabolism, Tumor Growth, and Metastasis
The overall goal of this project is to develop new therapeutic approaches to inhibit PDAC malignancy.

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U01 CA176110
PI: Kathleen Schmainda
Quantitative (Perfusion and Diffusion) MRI Biomarkers to Measure Giloma Response
This U01 application proposes the development and validation of a combined perfusion and diffusion MRI (magnetic resonance imaging) methods for use in clinical trials to evaluate the response of brain tumors to targeted therapies. Given that standard MRI methods to monitor treatment response have been found lacking this addresses an urgent clinical need. The perfusion technology is based on developments made over the past 12 years in the PI's laboratory and therefore may represent the most comprehensive and accurate solution to monitoring tumor vessel growth. This combined with recent advances in diffusion imaging, which provide complementary information about tumor cell invasion, has the potential to change the way by which brain tumor treatments are monitored and aid in the discovery of new treatments and combinations. Finally, working in close collaboration with an industrial partner, the proven technical methods resulting from this study will be translated into a low cost commercial software platform for widespread use within the QIN and beyond.

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UF1 AG051216

MPI: Shi-Jiang Li / Barbara Bendlin
Alzheimer’s Disease Connectome Project
The long-term goal of this project is to apply the Human Connectome Project (HCP) data collection protocol and develop robust technology to accurately stage AD across the full spectrum of its progression on an individual subject basis.

Interested in participating?

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Cancer Center Pilot Grant

PI: Jacek Zielonka
MCW Cancer Center
Targeting Mitochondria with Redox Cycling Agents to Overcome Drug Resistance in Human Colon Cancer Cells
Resistance of cancer cells to chemotherapy is an important factor leading to poor prognosis of cancer patients, despite the impressive advances in the anticancer therapeutic strategies over the last 20 years. Drug-resistant cells rewire their metabolism network, often with increased reliance on mitochondria to produce energy. We will design, synthesize, and evaluate the antiproliferative and cytotoxic potential of new redox cycling agents targeted to cancer cell mitochondria, in wild-type and drug-resistant colon cancer cells. These compounds are designed to inhibit mitochondrial respiration and induce oxidant stress in cancer cells. At the conclusion of these studies, we will have determined the potential of targeting redox-active drugs to mitochondria to inhibit proliferation and kill drug-resistant cancer cells.

Froedtert Hospital Foundation Grant

PI: Kathleen Schmainda
Froedtert Hospital Foundation
Obtaining Preclinical Evidence for a Novel Iron-Targeted Therapy for Glioblastoma

New Faculty Pilot Grant

PI: Michael Lerch
Molecular Mechanisms of Endogeneous Modulators of Beta2-Adrenergic Receptor Signal Transduction