FACULTY REU MENTORS FOR SUMMER 2024 AND THEIR RESEARCH INTERESTS:
Dr. Donald F. Becker Department of Biochemistry
Redox metabolism and enzymology
The overall goal of our research is to understand the mechanisms of metabolic enzymes and how metabolism impacts stress response and the intracellular redox environment. Of particular focus is on the metabolism of the amino acid proline. Students in our lab will gain experience in techniques for purifying and characterizing proteins and enzymes, cell culturing, and biophysical methodologies.
Dr. Liangcheng Du Department of Chemistry
Discovery of new antibiotics
REU students will learn how to isolate and identify new bioactive natural products from underexplored microorganisms. They will be exposed to techniques in microbial fermentation, metabolite analysis, biosynthetic gene identification and mutation, cloning and expression, biosynthetic enzyme activity assay, and metabolic pathway engineering. The outcomes will contribute to the on-going fight against multidrug-resistant pathogens.
Dr. Lindsey Crawford Department of Biochemistry
Viral control of stem cell fate
Our lab studies how viruses manipulate the human immune system. Specifically, we are focused on how common human herpesviruses infect and control hematopoietic stem cells (the foundational cell for the immune system). Projects in the lab address fundamental questions about viruses, stem cells, and immune system development; and students will learn to use tools and techniques from biochemistry, virology, immunology, and stem cell biology. Our primary herpesvirus, human cytomegalovirus, controls fundamental cellular pathways including suppression of reactive oxygen species and activation of glycolytic flux to regulate cell processes essential for the viral lifecycle. In turn, stem cells also closely regulate these processes to control fundamental processes of quiescence and proliferation. Understanding how these viruses control fundamental cell processes in stem cells is key to understanding disease and fundamental biology. Specifically, REU students will learn foundational molecular biology techniques to clone and analyze viral proteins to explore how protein interactions and regulatory domains alter cellular proliferation, differentiation, maintenance, and how these proteins contribute to the viral lifecycle. A specific focus is on the role of the HCMV RL11 genes (of unknown function) on regulation of redox homeostasis. Research training will be provided in molecular biology, protein biochemistry, virology, and cell biology. Overall, the lab asks questions aimed at developing a more complete picture of human immune system development, disease pathogenesis, and intrinsic mechanisms of stem cell biology.
Dr. Rodrigo Franco-Cruz Department of Veterinary and Biomedical Sciences
Redox homeostasis and energy metabolism
The Franco lab aims to understand the signaling mechanisms by which cellular metabolism, redox homeostasis and signaling regulate cellular fate. Mitochondrial dysfunction, alterations in protein quality control mechanisms and the activation/impairment of cell death pathways (apoptosis, necrosis and autophagy) have been associated with the etiology of human diseases. Energy failure and oxidative stress have been implicated in the induction of cell death, but the molecular mechanisms that link redox homeostasis and cellular metabolism to the activation of cell death pathways remain elusive. Our primary focus is to understand molecular mechanisms of neurotoxicity associated with environmental exposures, neurodegeneration, brain ischemia, and viral infections.
Dr. Katarzyna Glowacka Department of Biochemistry
Redox regulation of photosynthesis processes
Plants experience rapid fluctuations in the light, resulting from both cloud and leaf movements. In the absence of buffering mechanisms, rapid increases in light intensity can produce singlet oxygen and other reactive oxygen species (ROS) that can damage cells. Plants have evolved non-photochemical quenching (NPQ) to safely dissipate excess energy absorbed as heat. Uniquely, NPQ is regulated by redox and regulates the redox of other proteins including the first stable acceptor of the electron transport chain, quinone A (QA). A main goal of the Glowacka lab is to understand how NPQ is regulated under control and stress conditions. Recently, they identified uncharacterized thioredoxins (TRXs) to be involved in the regulation of NPQ. TRXs are oxidoreductases that regulate proteins via reversible modification of thiols. REU students will be involved in various aspects of biophysical, physiological and molecular biological analyses of NPQ-related TRXs. Students will use fluorescence imaging to quantify the kinetics of NPQ, photosystem II and QA redox states and spectrometry to assess photosystem I redox state and ATP-synthases activity. Students will also contribute to the molecular characterization of lines with mutations and overexpression of TRXs. In a second project, students will help characterize the lines with stress-conditional upregulation of NPQ that modifies QA redox state via which the closing and opening of leaf pores can be modulated.
Dr. Yihe Huang Department of Biochemistry
Transmembrane proteins are a crucial class of biomolecules that span the cell's lipid bilayer and play pivotal roles in cellular communication, transport of molecules, and signal transduction. These proteins are embedded within the cell membrane, with parts of their structure situated on both the extracellular and intracellular sides. The Huang lab use single-particle cryo-electron microscopy (cryo-EM) to comprehend the molecular mechanisms of transmembrane signaling at the atomic level. Redox modification of specific amino acids can induce changes in protein structure, affecting their capacity to transport molecules, transmit signals, or interact with other molecules. The delicate balance and characterization of the redox properties of membrane proteins are crucial prerequisites for subsequent structural studies and for comprehending the role of redox in transmembrane signaling. REU students will be engaged in multiple research aspects to characterize the redox properties of membrane proteins, including but not limited to molecular cloning for modifying redox-sensing residues, in vitro biochemical modifications of membrane proteins, high-throughput fluorescence-detection size-exclusion chromatography (FSEC), fast protein liquid chromatography (FPLC), cryo-EM, and structure analysis and presentation.
Dr. Oleh Khalimonchuk Department of Biochemistry
Redox regulation of mitochondrial processes
The Khalimonchuk laboratory seeks to understand processes that preserve normal mitochondrial functions during homeostatic challenges such as changes in nutrient availability, oxidative damage, and protein misfolding. The current research focus is to delineate the roles of several conserved redox-regulated proteases that are critical for mitochondrial protein quality control and energy metabolism. REU students will investigate mitochondrial proteases such as metallopeptidase Oma1 and serine proteases CLPXP and LACTB to elucidate the mechanisms of redox-tuned activation of mitochondrial protein quality control. Using yeast and mammalian cell culture systems, state-of-the-art genetics and biochemical approaches, and various physiological and imaging techniques, students will: 1) assess the impact of site-specific mutations of redox-sensitive residues on the function, stability, and activity of mitochondrial proteases; 2) analyze physical and genetic interactions of said enzymes by proteomic approaches, and reverse genetic screens; and 3) determine physiological penalties of the proteases’ inactivation and relevant signaling cues associated with the deficit. These multifaceted training activities will expose students to a variety of modern experimental approaches in molecular genetics, cell biology, and protein biochemistry. Trainees will also develop critical thinking and scientific communication skills by participating in weekly research meetings in the Khalimonchuk laboratory.
Dr. Jaekwon Lee Department of Biochemistry
Mechanistic insights into homeostasis of inorganic elements
Dr. Lee's research program focuses on identifying and characterizing molecular factors involved in the homeostasis (uptake, utilization, and detoxification) of inorganic elements and their functional roles in fungi and mammals. Inorganic elements are vital to sustaining all living organisms by supporting numerous biological processes, such as energy generation, membrane potential, and signaling; therefore, their deficiency and toxicity are associated with critical issues we have faced, such as food production and human and animal health. Dr. Lee's group has cloned copper, cadmium, and potassium transporters and elucidated their functions, action mechanisms, and regulation. REU students will determine the structure-function relations of copper, cadmium, and potassium transporters and the mechanisms underlying detrimental effects associated with the imbalance of these inorganic elements. Students will employ molecular genetics, biochemistry, bioinformatics, and cell biology approaches to identify the structural determinants of the transporters' binding and translocation of metals. REU students will also define the effects of inorganic element homeostasis perturbation on signaling pathways involved in growth, development, and death.
Dr. Xinghui Sun Biochemistry
Protein post-translational modification in cell death and vascular homeostasis
Sun’s group is interested in elucidating the uncharacterized role of protein neddylation in regulating cell death, redox homeostasis, and vascular integrity. Protein neddylation is one type of post-translational modification that regulates protein function and stability. Sun lab employs various approaches including molecular and cellular techniques, mouse models of human diseases, immunohistochemistry, multi-omics (e.g., genomics, transcriptomics, proteomics), and bioinformatics to discover new knowledge in biochemistry, vascular biology, and human diseases, which provides an excellent training opportunity for students interested in basic biomedical research. Specifically, students will have opportunities to conduct the following projects: 1) study redox and neddylation interaction in controlling protein function by doing cell culture, molecular cloning, immunoprecipitation, and mass spectrometry; 2) examine protein neddylation in human endothelial cell death by doing ELISA assay, cell culture, flow cytometry, and confocal imaging; and 3) characterize atherosclerotic lesion formations in mice by doing real-time qPCR, immunostaining, and histological analysis. Students also have opportunities to analyze multi-omic datasets.
Dr. Mark Wilson Department of Biochemistry
Time-resolved structural biology of redox-related proteins
A primary goal of the Wilson laboratory is to understand the physical basis of enzyme catalysis and protein signaling using time-resolved X-ray crystallography, cryo-EM, and other biophysical techniques. The advent of X-ray free electron laser (XFEL) sources and high resolution cryo-EM provides two distinct approaches for the detailed structural characterization of biochemical phenomena at multiple timepoints after perturbation. With these time-resolved “movies” of proteins in action, the Wilson lab investigates the non-equilibrium structural biology of several systems, including cysteine-dependent enzymes that form mandatory covalent reaction intermediates, proteins involved in antibiotic synthesis and destruction, and proteins that are important in redox biochemistry. Candidate projects for REU students include: 1) uncovering new mechanisms for enzymes in the DJ-1 superfamily using time-resolved X-ray crystallography, 2) determining the structures of large protein quality control assemblies, and 3) development of new experimental approaches to time-resolved structural biology using combined imaging approaches. REU students will gain experience in structural biology, molecular genetics, cryo-EM, and redox protein biochemistry.
Dr. Tatsuya Yamada Department of Biochemistry
Nexus of brain and liver - Physiological regulation of energy metabolism
The regulation of energy metabolism occurs seamlessly within our body. Multiple organs work together without our conscious awareness, supplying energy to sustain life in various environments and diverse circumstances. Yamada Laboratory is dedicated to achieving a comprehensive understanding of physiological energy metabolism. Our research focuses on the interaction between the brain and the liver, since the brain is the conductor of the physiological system, while the liver plays a key role in regulating its metabolism. As the liver is the primary organ for processing nutrients and xenobiotics, it undergoes a variety of redox reactions. REU students will be actively involved in research that addresses the regulation of redox reactions in hepatocytes within the context of physiological energy metabolism. Specifically, students will extract proteins from frozen samples of mice tissues and conduct biochemical analyses to understand whether proteins of interest are up- or down-regulated in hepatocytes upon activation of sympathetic nerves that innervate the liver. Additionally, students will contribute to identifying the molecular signaling pathways that respond to neural inputs and change the cellular metabolism in the liver, utilizing molecular biology techniques.
Dr. Limei Zhang Department of Biochemistry
Structures and mechanisms of metalloproteins
Transition metals play essential roles in a broad range of biological processes and are widely used in bacteria as redox stress sensors. A major research goal of the Zhang group is to develop a better mechanistic understanding of the structure and function of metal-binding proteins at the atomic level using molecular biological, structural, and spectroscopic approaches. REU students will be involved in various aspects of the structural and functional characterization of these metal-binding proteins. Specifically, REU students will clone, purify and characterize the wild-type and mutant metal proteins by spectroscopic approaches in vitro, in order to understand how protein folding dictates the stability and redox chemistry of the metal-binding proteins. The students will be trained to use structural approaches (crystallography and cryoEM) to characterize these proteins. These projects will provide unique research training for REU students in molecular biology, redox protein biochemistry and structural biology.