Metabolism Directory

Merrins, Matthew

Assistant Professor Medicine (716) 397-7557

My lab is focused on understanding oscillatory metabolic signaling in the pancreatic islet and its deficiency in type 2 diabetes. My lab specializes in single-cell approaches – principally live-cell imaging and electrophysiology – and since the lab’s inception we have developed a number of exciting tools which have given us new insights into diabetes pathophysiology. One example is fluorescence lifetime imaging of NADH (FLIM-N), which allows us to distinguish metabolic activity in each subcellular compartment of the pancreatic beta cell, including the mitochondria. Using FLIM-N and FRET imaging, we hope to understand the bidirectional communication between mitochondrial metabolism and the cell cycle machinery, mediated by cyclin dependent kinases. We are also focused on characterizing a number of mitochondrial proteins initially identified by RNA-seq as type 2 diabetes-associated loci; in this case, we are using Phy-PIF optogenetics to elucidate the mechanisms by which these proteins alter mitochondrial dynamics, metabolic oscillations, and insulin secretion.

Eisenstein, Rick

Professor Nutritional Sciences (608) 262-5830

We study mechanisms of iron sensing and control of iron homeostasis in vertebrates by iron regulated RNA binding proteins, the iron regulatory proteins (IRP). IRP maintain iron homeostasis by controlling the fate of mRNA encoding proteins needed for iron metabolism or the responses to iron deficiency. We investigate how iron metabolism and erythropoiesis is coordinated particularly how IRP1 senses iron or oxygen status and controls the translation of hypoxia inducible factor 2-α (HIF-2α) mRNA. HIF-2α, a transcription factor, promotes adaptive responses to hypoxia by enhancing both red blood cell production and dietary iron acquisition for hemoglobin production. We use animal, cell culture and model systems (yeast) to define the physiological roles of IRP1, its selective control of mRNA fate and the iron trafficking pathways it responds to. Genome editing, flow cytometric analysis of hematopoiesis, RNA binding, gene by diet interaction studies, tissue specific knockouts and in vivo imaging.

Keller, Mark

Distinguished Scientist Biochemistry (608) 263-4234

I have worked closely with Professor Alan Attie for more than 16 years to integrate genetics, physiology and metabolism to better understand the molecular basis of disease susceptibility. The lab exploits natural genetic variation contained within in-bred mouse strains as a platform to link metabolic disease with genetics. One major project is focused on surveying diet-induced metabolic syndrome in a newly developed mouse resource called the Diversity Outcross (DO). Each DO mouse derives from 8 distinct parental mouse strains that together represent the genetic diversity contained within the human population. The degree of metabolic syndrome we observe in the DO population is remarkable, illustrating that phenotypic variation is driven by genetic variation. We employ various omics-based measurements (e.g., transcriptomics, proteomics, microbiomics, metabolomics) to generate robust causal models that will help to unravel the enormously complex relationship between the genetics of each DO mouse and their relative susceptibility to metabolic syndrome.

Yen, Eric

Associate Professor Nutritional Sciences (608) 890-1888

We are interested in understanding how cellular metabolism modulates systemic energy balance in response to diet. Our research centers on the synthesis of triacylglycerol, which serves as a storage and transport molecule of bioactive fatty acids and excess calories. Using genetically engineered mice, we examine the physiological functions of enzymes involved in the process. One current focus is on monoacylglycerol acyltransferase 2, which mediates the absorption of dietary fat in the small intestine. Mice lacking the enzyme are protected against obesity and other metabolic disorders normally induced by high-fat feeding. Interestingly, these mice absorb a normal quantity of fat but exhibit increases in energy expenditure. We are now combining biochemical and systems biology approaches to understand the underlying molecular mechanisms. The ultimate goals are to better understand the fundamental process of fat assimilation and to explore new approaches to prevent obesity and other metabolic diseases associated with excessive energy storage.

Engin, Feyza

Assistant Professor Biomolecular Chemistry (608) 262-8667

Our lab is interested in understanding the role of organelle stress and stress responses in disease pathogenesis. The endoplasmic reticulum (ER) orchestrates protein synthesis, folding and trafficking in the cell and disruption of the ER's adaptive capacity results in activation of the unfolded protein response (UPR). Under chronic stress conditions, UPR engage many different inflammatory and stress signaling pathways that are critical for disease pathologies including insulin resistance, obesity and type2 diabetes. Interestingly, we recently discovered that ER stress plays a significant role in the pathogenesis of not only type 2 diabetes, but also autoimmune diabetes. Currently, we are exploring the molecular mechanisms leading to ER stress in type 1 diabetes and investigating the role of different UPR branches in metabolic homeostasis. We are also investigating how disruption of ER calcium homeostasis may affect interactions between ER and mitochondria in the context of metabolic and autoimmune diseases.

Krautkramer, Kimberly

Graduate Student Biomolecular Chemistry & Wisconsin Institute for Discovery (608) 890-4224

As a graduate student in the John Denu lab, I focus on linking alterations in metabolism to changes in the epigenome. Toward this end, I use a variety of tools, including mass spectrometry to measure changes in histone PTMs and small molecule metabolites. I am currently studying effects of gut microbial metabolites on host epigenetic regulation across multiple organ systems.

Klein, Mark

Graduate Student Biomolecular Chemistry (847) 436-2823

Sirtuin 6 is an NAD-dependent protein deacylase that regulates lipid and glucose homeostasis. Recently, we have discovered that Sirt6 can be activated by endogenous compounds in vitro. I am continuing to discover endogenous activators and aim to understand if this activation plays a role on Sirt6 metabolic regulation in vivo.

Hernandez, Laura

Assistant Professor Dairy Science (608) 263-9867

Our research is focused on how serotonin controls maternal metabolism to support lactation. We focus on two areas of how the mammary gland controls maternal metabolism during lactation: calcium homeostasis and energy homeostasis. We utilize rodent and cow in vivo models and as well in vitro techniques.

Cook, Mark

Professor Animal Sciences (608) 212-5874

We study changes in metabolism caused by inflammatory processes in animals and humans. During acute and chronic inflammation, nutrient metabolism favors immune defense as opposed to growth or weight maintenance. We develop technology to mitigate and monitor changes in metabolism. Our breath biomarkers of inflammation (Isomark.com) are used to detect onset of infection. We target secretory phospholipase A2 and construct intestinal barrier strategies to prevent the feed forward loop of the intestinal in inflammation (Ovabio.com). Recently we discovered that intraluminal targeting of IL-10 prevents intestinal protozoan infection in chickens, and respiratory disease in cattle (Ab E Discovery). Conjugated linoleic acid is another product that has been shown to mitigate inflammatory processes that affect nutrient metabolism (BASF, Stephan). Our work and technologies span animal agriculture to human medicine.

Knoll, Laura

Associate Professor Medical Microbiology and Immunology (608) 262-3161

Our research centers on studying the host/pathogen interactions for the intracellular parasite Toxoplasma gondii. Toxoplasma is a highly successful parasite that exists as a life-long infection in a large percentage of the world’s warm-blooded animals, including almost half the human population. In a healthy individual, Toxoplasma has evolved to stimulate, but not over-stimulate the host’s immune response. Toxoplasma causes encephalitis in immunocompromised patients and is a member of the coccidian family that includes Plasmodium. We are combining next generation sequencing, proteomics and metabolomics to uncover the host and parasite metabolic pathways that are necessary for Toxoplasma to establish and maintain chronic infection. Because Toxoplasma is auxotrophic for many essential nutrients, we are finding that infection dramatically manipulates host cell metabolism. Toxoplasma also has both a mitochondria and a remnant chloroplast, so it has several unusual metabolic products. These studies will generate new anti-parasitic targets that will help develop novel therapies.

Coe, Christopher

Professor Psychology (608) 263-3550

My research spans a number of topics in behavioral medicine and health psychology, which involve metabolism. Using a nonhuman primate model, we are investigating the relationship between the gut microbiome and systemic physiology during infancy. We also are studying novel iron supplements to treat iron deficiency anemia, and include metabolomic approaches to assess the benefits of treatment. Our research with human participants is focused more on the other end of the life span, and the biology of aging. My lab oversees the biomarker assessments for 2 surveys of health and aging in the US and Japan (MIDUS and MIJDA). Both include a number of outcomes related to metabolism, especially with respect to obesity and glucoregulation.

Sutula, Thomas

Professor Neurology (608) 263-5448

My interest and ongoing work addresses the influences of glycolysis and metabolism on neuronal and circuit function in the brain.

Converse, Alexander

Senior Scientist Waisman Center (608) 265-6604

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) to noninvasively image glucose metabolism

Baker, Mei

Co-Director, Newborn Screening Laboratory Wisconsin State Laboratory of Hygiene (608) 890-1796

My research interest is public health genetics and genomics, with a focus on applying and translating advanced biochemical and molecular technologies into routine newborn screening practice to enable public health laboratories to screen for new conditions and improve screening performance for the exiting screened conditions.

Reed, Jennifer

Associate Professor Chemical and Biological Engineering (608) 772-6226

Systems biology studies biological networks at a systems- or network-level in order to understand and predict cellular behaviors. Our research group studies microbial metabolism and regulation using a combination of computational and experimental approaches. We utilize computational models to study microbial systems, engineer cells, and expand our knowledge of the underlying mechanisms behind observed metabolic behaviors. We are interested in studying microbes (and microbial interactions) involved in metabolic engineering, health, and bioremediation applications. Our models can integrate diverse sets of experimental data to describe and predict the structure and activity of cellular networks. We are interested in identifying novel enzymes and/or reactions, transcriptional regulatory interactions, and inter-species interactions to further elucidate genotype-phenotype relationships. We are also interested in quantifying network activities using a variety of experimental (e.g.,13C metabolic flux analysis) and computational tools (e.g., constraint-based and kinetic models). Developed models allow us to systematically evaluate the capabilities of different organisms from a network-based perspective and to identify ways in which genetic or environmental manipulations could enhance desired activities (e.g., chemical production) or prevent un-desirable states (e.g., disease).

Donohue, Timothy

Director Great Lakes Bioenergy Bacteriology (608) 262-4663

Bacterial metabolism and energy generation, this include central carbon and nitrogen metabolism, aromatic utilization and control of these pathways. We use genetic, biochemical genomic and other approaches in a wide set of microbes, but pure cultures and consortia or simple microbiomes

Fan, Jing

Morgridge Fellow Morgridge Institute for Research (608) 316-4695

Our lab is interested in understanding how mammalian cellular metabolism is reprogrammed in response to changes in the environment and cellular state, and how activities in key metabolic pathways can in turn affect cell function. To study this, we combine systems biology approaches, especially fluxomics and metabolomics, with computational modeling and biochemical and genetic techniques. Particularly, our current works focus on (1) understanding the metabolic adaptations in cancer cells in acidic microenvironment, and (2) investigating the metabolic regulation during macrophage polarization

Eide, David

Professor and Chair Nutritional Sciences (608) 263-1613

My lab studies the mechanisms cells use to respond and adapt to metal nutrient deficiencies. We study these processes in the yeast Saccharomyces cerevisiae and focus primarily on zinc deficiency. In this yeast, the Zap1 transcription factor responds to zinc deficiency to activate the expression of ~80 genes. The products of these genes include several zinc transporters responsible for zinc homeostasis. Many Zap1-regulated genes also encode proteins involved in the adaptation to zinc deficiency including proteins involved in oxidative stress resistance, protein homeostasis, sulfur metabolism, and phospholipid synthesis.

Newton, Michael

Professor Biostatistics & Medical Informatics (608) 262-0086

I do statistics and biostatistics, especially in genomic apps, and have collaborated on various projects that integrate different data sources

Conklin, Matthew

Associate Scientist Cell and Regenerative Biology (608) 265-5094

Part of my research is the imaging of the metabolic cofactors NADH and FAD though the technique of Fluorescence Lifetime Imaging Microscopy (FLIM). The measurement of the lifetimes of these cofactors is a non-invasive method that can be performed on tissue slides and may help in the diagnosis of diseases.

Carey, Hannah

Professor Comparative Biosciences (608) 263-0418

Metabolic adaptations in hibernating mammals, including basic mechanisms and biomedical implications. Current focus on gastrointestinal/liver physiology and the microbiome.

Nelson, David

Assistant Scientist Nutritional Sciences (608) 890-2105

I am interested in elucidating the interaction between cellular processes and whole body energy metabolism. In our research group, we use molecular genetics to modulate the function of genes involved in lipid metabolism. My primary focus is on the role of intestinal monoacylglycerol acyltransferase 2 (MGAT2), an enzyme that catalyzes the conversion of MAG to DAG (an essential step in the efficient absorption and assimilation of dietary fat), in mediating systemic responses to diet. Using indirect calorimetry, I am linking alterations in food intake, oxygen consumption (VO2), and substrate utilization (RER) with diet and environmental challenges in genetically engineered mice. In particular, I am investigating MGAT2’s role in intracellular lipid trafficking and effects on enteroendocrine signaling and the kinetics of nutrient absorption and delivery. Through this research, we hope to better understand how alterations in the kinetics of intestinal lipid metabolism affect whole body energy metabolism, obesity, and related morbidities.

Jefcoate, Colin

Professor Cell & Regenerative Biology (608) 263-3975

The Laboratory addresses signaling processes involved in adaptation to Diet, Chemicals and Stress. Mesenchymal cells are key mediators, which include multi-potential progenitor cells that deliver physical structure, energy control (adipose), steroid production and local support factors. The Laboratory played key roles in the discovery of two regulators of these processes; Cytochrome P450 1B1 (CYP1B1) and the Steroidogenesis Acute Regulator (StAR). CYP1B1 is expressed in mesenchymal progenitors and vascular cells, but also controls oxidative stress, vascular adhesion and monocyte differentiation. We probe CYP1B1 functions through general and selective deletions of CYP1B1 from mice, facilitated by the development of a flox/flox Cyp1b1 mouse (gene expression/associated physiological changes). Hormonal activation of StAR, a labile protein, directs delivery of cholesterol to Cyp11a1 in mitochondria, thereby initiating adrenal glucocorticoid synthesis, a mediator of liver energy homeostasis or testosterone synthesis in fetal and adult testis, a notable source of endocrine disruption.

Fox, Brian

Professor Biochemistry (608) 262-9708

Protein structure and function. Oxidation and reduction reactions. Fatty acid metabolism. Production of biofuels and other products from cellulosic biomass.

Racine, Natalie

Senior Research Specialist UW Biotechnology Center (608) 263-5477

We are a core lab using the doubly labeled water method to measure body composition and energy metabolism primarily in humans. We also have a room calorimeter at the UW Hospital as well as a cart for resting energy expenditure via respiratory gas exchange.

Colopy, Sara

Clinical Instructor Surgical Sciences (608) 262-4580

My laboratory is focused on understanding the pathogenesis of urinary tract infection and bladder epithelial healing. One current area of research is looking at the pathogenesis of urinary tract infections in type II diabetic mice.

Lin, Yuan

Research Associate Horticulture (608) 335-8663

The metabolism finger print during Plant-Pathogen interaction.

Pagliarini, Dave

Lead Investigator of Metabolism Biochemistry (608) 316-4664

My group investigates the core metabolic and biochemical functions of mitochondria, and how the dysfunction of these processes gives rise to diverse human disease. We are particularly interested in systematically annotating the functions of uncharacterized mitochondrial proteins and in elucidating how these proteins are regulated by post-translational modifications. To do so, we integrate large-scale experimental and computational methodologies with mechanistic and structural biochemistry approaches.

Landick, Robert

Charles Yanofsky Professor of Biochemistry and Bacteriology Biochemistry (608) 265-8475

We study the regulation of RNA synthesis by RNA polymerase and the use of gene expression engineering to create novel microbial systems and communities to produce beneficial compounds and materials. These studies link to metabolic regulation through a diverse set of protein, RNA, and small molecule regulators that interact with RNA polymerase to control gene expression, in the search for new inhibitors of RNA polymerase as lead compounds for drug discovery, and via ways that changes in gene expression can redesign metabolism for useful purposes.

Denu, John

Professor Biomolecular Chemistry (608) 316-4341

Linking metabolism with the epigenome: Chromatin remodeling enzymes rely on co-enzymes derived from metabolic pathways, suggesting coordination between nuclear events and metabolic networks. Investigations are underway to understand the link between metabolism and the regulation of epigenetic mechanisms. We are testing the hypothesis that certain chromatin modifying complexes have evolved to exquisitely ‘sense’ metabolite levels and respond accordingly, modifying specific chromatin loci for altered gene expression. Sirtuins and reversible protein acetylation: Accumulating evidence suggests that reversible protein-lysine is a major regulatory mechanism that controls non-histone protein function. Sirtuins are a conserved family of NAD+-dependent protein deacetylases that have emerged as important players in modulating protein acetylation. Compelling genetic evidence implicates sirtuins in genome maintenance, metabolism, cell survival, and lifespan. The NAD+-dependence suggests that specific protein deacetylation is inextricably linked to metabolism. We are examining the central hypothesis that reversible protein acetylation is a major regulatory mechanism for controlling diverse metabolic processes, and that at the molecular level, site-specific acetylation alters the intrinsic activity of targeted proteins.

Barkal, Layla

Graduate Student Biomedical Engineering (319) 431-4861

We are interested in host-pathogen interactions mediated by secreted metabolites originating both from the invading pathogen and from the responding host immune cells. The signaling molecules are chemically diverse and the milieu is highly dynamic. To address these challenges, we develop microfluidic devices that leverage physical principles of surface tension at microscale to generate passive biphasic systems for the extraction of small molecules including fungal secondary metabolites and immunomodulatory oxylipins. These same physical principles also enable us to design devices for co-cultures of organisms across kingdoms while still allowing for extraction from each compartment separately. Extracted small molecules can then be channeled into the existing metabolomics workflow and analyzed using LC-MS, creating a powerful workflow.

Markley, John

Professor Biochemistry (608) 263-9349

Our major interest is in NMR-based investigations of metabolites and their interactions. NMR allows unbiased detection and quantification of the 30-80 most abundant metabolites in biological fluids and tissue extracts. We created a database of one- and two-dimensional spectra of metabolites and other small molecules of biological importance, which has grown to include ~1400 compounds. We developed efficient technology for high-throughput data collection, automated assignment and quantification of individual species and visual inspection of the results. We recently developed a platform for rapid screening of proteins against a panel of 500 metabolites to determine whether the protein binds or chemically modifies these small molecules. In favorable cases, we can use NMR to validate hits and to determine ligand binding sites. In the realm of natural products, we provide technology for LC-MS with solid phase extraction so that molecules with a mass of interest can be isolated for subsequent NMR analysis.

Veling, Mike

Graduate Student Biochemistry (617) 291-1943

I use a hybrid approach of computational systems biology and biochemistry to determine the function of mitochondrial proteins.

Olson, William

Graduate Student Medical Microbiology and Immunology (503) 737-8375

I study the interconnected host-pathogen metabolome of the obligate intracellular parasite Toxoplasma gondii, using human tissue culture infection models. I profile infection broadly with transcriptomics and metabolomics, and more narrowly with siRNA, CRISPR knockout parasites, isotopic metabolite labeling, and pathogenesis assays.

Farrugia, Mark

Research Associate Medicine (313) 283-1851

My work is focused on determining the structures of components of the endoplasmic reticulum-resident acetyl-CoA transporters/transferases. This pathway has been shown to be a druggable target in a mouse model to prevent the development of Alzheimer's disease. Several compounds have been developed to inhibit this pathway and promote autophagy, but structural information on the players in the pathway would allow for more effective inhibitors to be developed.

Lamming, Dudley

Assistant Professor Medicine (608) 256-1901

The Lamming laboratory's goal is to understand how nutrient-responsive signaling pathways can be harnessed to promote health and longevity. We are primarily focused on the physiological role played by the mechanistic target of rapamycin (mTOR), a protein kinase that through a diverse set of substrates regulates complex cellular processes, including growth, metabolism, and aging. Recent work has shown that rapamycin, an inhibitor of mTOR signaling, can improve both health and longevity in model organisms including mammals. Understanding and manipulating the mTOR signaling pathway through dietary, pharmaceutical or genetic interventions in mouse models may provide insight into the treatment of age-related diseases, including diabetes, Alzheimer's disease, cancer, and Hutchinson-Gilford Progeria Syndrome. Learn more at http://www.lamminglab.org/

Ane, Jean-Michel

Professor Bacteriology (608) 262-6457

Our primary research interest is understanding the molecular mechanisms controlling symbiotic associations between plants and microbes, and the application of this knowledge to maximize the benefits of such associations in agriculture. We particularly focus on two types of associations: nitrogen-fixing associations with bacteria and mycorrhizal associations with fungi. One component of our research is to look at the effect of these associations on plant and microbial (bacteria and fungi) metabolism at different stages of these associations.

Alexander, Caroline

Professor Oncology (608) 265-5182

We aim to determine the role of a skin-associated lipid layer, we call dermal white adipose tissue, on mammalian insulation, and therefore on glucose disposition and the frequency of thermogenic activation of brown adipose tissues. We propose that manipulation of this dWAT layer could confer health benefits to human subjects. Our research is enabled by the development of a high resolution, body wide quantitative MRI technique

Dowell, James

Associate Scientist Wisconsin Institute for Discovery (608) 306-4449

My research is focused on the metabolism of the brain. Specifically, I am interested in metabolic processing of glutamate in astrocytes, its regulation by protein kinases, and its involvement in neurodegeneration. I use both mass spectrometry-based metabolomics and proteomics platforms to study these processes.

Westmark, Cara

Senior Scientist Neurology (608) 262-9730

My research interests lie in the area of synaptic function as related to the over-expression of amyloid-beta protein precursor and amyloid-beta in Alzheimer’s disease, Down syndrome and fragile X syndrome. I study therapeutic approaches that reduce amyloid-beta and rescue seizure, behavioral, cognitive and biomarker phenotypes associated with the aforementioned disorders. During the course of these studies, I serendipitously discovered that diet, specifically soy-based diets, exacerbate seizure incidence and weight gain in juvenile mice as well as in infants. Soy is rich in phytoestrogens and contaminated with agrochemicals, which can act as endocrine disrupting chemicals. Surprisingly, there has been a paucity of studies regarding the long-term effects of consuming singe-source soy-based diets. Our research focus in metabolism is to study the effect of soy on neurological and metabolic phenotypes, particularly in developmental disability models, to validate dietary restriction of soy-based infant formula as a therapeutic intervention for autism and fragile X.

Li, Lingjun

Professor School of Pharmacy (608) 265-8491

Our research focuses on the development of mass spectrometry-based tools and systems biology strategy to understand metabolic profile changes during various disease conditions such as aging, lower urinary tract symptoms, and cardiovascular injury. We also employ imaging MS technology to understand symbiosis between bacteria/microbiome and host organisms.

Romero, Pedro

Director BMRB Biochemistry (608) 265-5741

BMRB hosts a metabolite and small molecule NMR database useful for metabolomics studies, and it is involved in research and development of software tools to facilitate automatic metabolite identification from metabolomics profiles.

Dahlberg, Jim

Emeritus Professor Biomolecular Chemistry (608) 262-1459

Impact of physiology on metabolic states.

Suen, Garret

Assistant Professor Bacteriology (608) 890-3971

Our work focuses on understanding the rumen ecosystem with an toward improving animal production and utilizing this microbiome as a model for biofuel production. We utilize genome-enabled approaches to characterize and understand this community to determine if alterations to the rumen microbiome can result in increased animal production. From a biofuels perspective, our work seeks to determine how this highly optimized microbiome is capable of rapid biomass degradation and fermentation.

Ulrich, Eldon

Senior Scientist Emeritus Biochemistry (608) 215-6879

Database development for NMR

Lohman, Danielle

Graduate Research Assistant Biochemistry (608) 316-4331

Mitochondria—known as the powerhouse of the cell—are dynamic organelles that produce approximately 90% of our cellular energy in the form of ATP. One essential component of the mitochondrial machinery that produces ATP is Coenzyme Q (CoQ). Discovered at the University of Wisconsin over 50 years ago, CoQ is a redox active lipid whose deficiency is implicated in several human diseases. CoQ is synthesized inside mitochondria, yet many knowledge gaps surround its biosynthesis: What enzymes are involved? What are the molecular roles of proteins known to be involved? How is the biosynthesis regulated? Danielle’s doctoral research aims to fill these gaps, specifically to understand the role of COQ9, a protein of previously unknown function, in CoQ biosynthesis. She is particularly interested in protein-lipid interactions and has expertise in the culture of model organisms, lipid handling, molecular and structural biology as well as various biochemical and chemical methods.

Keller, Nancy

Professor Medical Microbiology and Immunology (608) 262-9795

My lab focuses on the genetics and chemistry of fungal natural products (NPs). We explore the role of NPs as virulence factors (particularly in Aspergillus and Penicillium species), as signaling molecules in intra- and inter-Kingdom milieus and for development as pharmaceuticals. We are interested in the crosstalk of primary and secondary metabolism in fungi and how natural product clusters are regulated by endogenous mechanisms (e.g. epigenetic regulation and global transcriptional regulators) or exogenous input from other organisms (e.g. other microbes or hosts) and abiotic factors.

Sinha, Divya

Postdoctoral Research Associate Waisman Center (div) ya.-sinha@wisc.edu

Human pluripotent stem cell derived retinal pigment epithelium (hPSC-RPE) and photoreceptor (hPSC-PR) cells are being utilized for in vitro modeling of retinal diseases as well as to develop cell replacement therapy for retinal degenerative diseases that lead to blindness. Since these retinal cell types are highly functional and mitochondria-rich in vivo, our efforts are focused on assessing and enhancing cell health of hPSC-derived RPE and photoreceptors in terms of mitochondrial metabolism under physiologic conditions.

Reidenbach, Andrew

Postdoctoral Fellow Metabolism (608) 316-4307

I’m interested in discovering missing pieces in established biochemical pathways within mitochondria, and I’m currently investigating the biosynthesis of coenzyme Q (CoQ). The UbiB family of protein kinase-like (PKL) genes are required for CoQ biosynthesis and have been conserved throughout evolution. I aim to discover substrates of this ancient PKL family.

Eells, Janis

Professor Biomedical Sciences at UWM and Ophthalmology at UW (608) 215-5405

Mitochondria play a key role in cellular metabolism and intracellular signaling. Mitochondrial dysfunction and the resulting oxidative stress are central in the pathogenesis of aging and degenerative diseases including diabetes, cardiovascular disease, macular degeneration and Alzheimer’s disease. Research in my laboratory is directed at understanding the mitochondrial signaling pathways that regulate the processes of cellular aging and degeneration with the long-term goal of learning how to protect cells and tissues against these degenerative processes. One mitoprotective strategy is photobiomodulation. Exposure to low energy photon irradiation in the far-red (FR) to near-infrared (NIR) range of the spectrum (630 – 900 nm), collectively termed “photobiomodulation” (PBM) can restore the function of damaged mitochondria, upregulate the production of cytoprotective factors and prevent apoptotic cell death. FR/NIR photons penetrate diseased tissues including the retina and optic nerve. Investigations in rodent models of retinal injury and disease have demonstrated the PBM attenuates photoreceptor cell death, protects retinal function and exerts anti-inflammatory actions. Recent clinical studies have documented amelioration of atrophic AMD.

Maeda, Hiroshi

Assistant Professor Department of Botany (608) 262-5833

The Maeda lab investigates how plants synthesize aromatic amino acids, which are essential nutrients in the human diet and key precursors of numerous plant natural products (e.g. alkaloids, quinones, phenolic compounds). We combine phylogenetic, biochemical, genetics, and protein structure analyses to understand how key enzymes in the aromatic amino acid pathways evolved in different plant lineages that produce distinct downstream specialized metabolites. Such evolutionary variations are then utilized to identify amino acid residues responsible for their catalytic and regulatory properties and also to enhance the production of natural products through metabolic engineering.

Dhillon, Rush

Research Associate Biomolecular Chemistry (608) 316-4426

I use a comparative approach to examine the physiological and biochemical response of organisms to stressors. Specifically, I am interested in aerobic pathways of metabolism in response to stress, and their implications for mitochondrial respiration. Currently, the focus of my research is to examine how acetylation and cellular redox status regulate mitochondrial metabolism and components of the electron transport system, in response to age.

Gamm, David

Associate Professor Department of Ophthalmology and Visual Sciences (608) 261-1516

Human pluripotent stem cell derived retinal pigment epithelium (hPSC-RPE) and photoreceptor (hPSC-PR) cells are being utilized for in vitro modeling of retinal diseases as well as to develop cell replacement therapy for retinal degenerative diseases that lead to blindness. Since these retinal cell types are highly functional and mitochondria-rich in vivo, our efforts are focused on assessing and enhancing cell health of hPSC-derived RPE and photoreceptors in terms of mitochondrial metabolism under physiologic conditions.

Cryns, Vincent

Professor Medicine (608) 262-4786

Tumor cells must adapt to metabolic stress intrinsic to their rapid growth in order to survive. Our group focuses on the molecular mechanisms by which tumor cells adapt to metabolic stress. We are also interested in targeting metabolic stress in tumor cells by depriving them of essential nutrients to metabolically prime them to respond to pro-apoptotic therapies. As a defining feature of cancer cells, metabolic stress offers unprecedented translational opportunities to selectively target cancer.

Parks, Brian

Assistant Professor Nutritional Sciences (608) 262-3445

The Parks Lab is focused on addressing the question of how genetics and diet interact together to contribute to common metabolic diseases, such as obesity and diabetes. Through the use of large-scale integrative genetic studies in the mouse we have identified several candidate genes that mediate gene-diet interactions. Current work is focused on a novel candidate drug target, Agpat5, which improves common symptoms of obesity and diabetes. In addition to this work we have a strong interest in the development of systems genetics approaches for dissecting biological pathways and networks.

Brow, Dave

Professor Biomolecular Chemistry (608) 262-1475

Metabolite-regulated gene expression in yeast. We identified a pathway for regulation of IMPDH synthesis by its end-product GTP via transcription attenuation. We are investigating additional levels of regulation using IMPDH-GFP and quantitative live-cell microscopy. Mutations in human IMPDH1 can result in an inherited form of blindness, retinitis pigmentosa, possibly by disrupting binding of IMPDH to its gene or mRNA. We are using yeast as a model system to study the effects of these disease mutations.

Amador-Noguez, Daniel

Assistant Professor Bacteriology (608) 265-2710

The production of biofuels from cellulosic biomass holds promise as a source of clean renewable energy that can reduce our dependence on fossil fuels. Attaining this goal will require engineered microorganisms capable of economical conversion of cellulosic biomass into biofuels. Effective microbe design relies on understanding the relevant metabolic pathways and their regulation, including how the integrated networks function as a whole. My research program integrates systems-level analyses, especially metabolomics, with computational modeling and genetic engineering to advance understanding of metabolism in biofuel producing microorganisms, particularly clostridium species such as C. acetobutylicum, C. cellulolyticum and C. thermocellum. The main research topics in my laboratory are: 1) Systems-level analysis of metabolic regulation in biofuel producing microorganisms and 2) Engineering symbiotic consortia for biofuel production.

Burkard, Mark

Associate Professor Medicine (608) 262-2803

My research is focused on identifying unique abnormalities of cancer cells, including metabolic alterations, that confer sensitivity to anticancer therapy, thereby enabling precision medicine.

Hittinger, Chris

Assistant Professor Genetics (608) 262-1069

We study the evolutionary genomics of yeasts with particular emphases on biodiversity and carbon metabolism. Over the last half a billion years, different yeast species have evolved radically different metabolic strategies, from the rare highly fermentative lifestyle of Saccharomyces (i.e. Crabtree-Warburg Effect or aerobic fermentation) to yeasts that accumulate over half of their dry weight as fatty acids. We use genetic, genomic, phylogenetic, and metabolic approaches to understand how these differences are encoded in their genomes. We also have applied projects in brewing, cellulosic biofuels, and synthetic biology.

Cobra, Paulo Falco

Research Associate Biochemistry (608) 770-0487

The main project I'm currently working on focus on the investigation of two different species of the protozoa responsible for the leishmaniasis disease and how their metabolism is affect by adding two of the current drugs used to treat the disease to the growth medium used to cultivate them. There are other collaboration projects in different segments being investigated simultaneously.

Kemnitz, Joseph

Professor and Vice-Chair Cell & Regenerative biology (608) 263-3588

calorie restriction and aging; T2DM

Audhya, Anjon

Associate Professor Biomolecular Chemistry (608) 262-3761

The Audhya lab is interested in the contribution of membrane transport pathways (both secretory and endocytic trafficking) to cellular metabolism as it relates to growth, development, endocrine function, and the regulation of lipid homeostasis.

Niemi, Natalie

Postdoctoral Fellow Metabolism (608) 316-4127

My research focuses on post-translational modifications and how these regulatory events can regulate metabolism. We are particularly interested in mitochondrial phosphorylation. While many phosphorylation events have been documented in the mitochondrion, only a handful are known to play a role in metabolic flux (e.g. phosphorylation of the pyruvate dehydrogenase complex). To further explore this question, we have recently coupled genetic loss-of-function studies with quantitative phosphoprotomics to identify a subset of mitochondrial phosphoproteins that may be regulated by a mitochondrial-localized phosphatase in yeast. We ultimately hope to understand how mitochondrial function is regulated by phosphorylation and whether this process can be exploited to treat the mitochondrial dysfunction associated with many diseases.

Kimple, Michelle

Assistant Professor Medicine-Endocrinology (608) 616-0138

G protein-coupled receptor signaling pathways affecting pancreatic beta-cell function, growth, and survival in normal and pathophysiological states.

Loewe, Laurence

Assistant Professor Laboratory of Genetics (608) 316-4324

Understanding metabolic networks is complicated and mechanistic simulations have been used for integrating much of the known observations. Much would be gained by providing experimental biologists with the possibility to describe the metabolic networks they study in a way that facilitates automated computational analyses. My lab has built a prototype of the Evolvix model description language that makes it easy to construct such models and enables the efficient collection of time series data from arbitrarily complicated pure mass-action kinetics simulations. We are currently working to extend this language into the first general purpose programming language designed by biologists for biologists. The purpose of this effort is to enable automated analyses of metabolic and other biochemical reaction networks in order to investigate their robustness in a broader evolutionary systems biology context.

Bates, Donna

Research Coordinator Great Lakes Bioenergy Research Center (608) 890-4843

I work in the Conversion Area of GLBRC where I help coordinate research on making biofuels from lignocellulosic biomass. This research relies heavily on an understanding of microbial metabolic pathways and ways in which they can be manipulated.

Puglielli, Luigi

Professor Medicine (608) 256-1901

Role of the endoplasmic reticulum (ER) acetylation machinery and intracellular acetyl-CoA flux in developmental and degenerative diseases.

Craven, Mark

Professor Biostatistics and Medical Informatics (608) 265-6181

Developing and applying methods from machine learning, natural language processing, and optimization to infer models characterizing networks of interactions among genes, proteins, metabolites, clinical variables, environmental factors, and phenotypes of interest.

Livny, Miron

Professor Computer Sciences (608) 320-9484

Distributed High Throughput Computing. Frameworks and software tools that enable researchers to run with the help of automation tools (workflows) large ensembles of interdependent jobs on large collection of distributed computing and data resources.

Sato, Trey

Senior Scientist Wisconsin Energy Institute (610) 551-5266

My group is interested in understanding the regulation of lignocellulosic sugar conversion into biofuels and bioproducts by Saccharomyces cerevisiae. We employ metabolomic, proteomic and transcriptomic tools to determine the molecular mechanisms by which genetically engineered and evolved yeast strains increase their rate of sugar metabolism.

Schaid, Mike

Graduate Student Nutritional Sciences (507) 269-8095

Our lab's primary focus is a unique signal transduction mechanism in pancreatic islets as it relates to the pathology of diabetes, in which both metabolism and cellular signaling are altered.

Fathi, Fariba

Research Associate Biochemistry (608) 262-1754

NMR-based metabolomics studies including: NMR sample preparation ; identification metabolites in biofluid by 1HNMR, 2D methods(TOCSY and HSQC); measure the concentration of metabolites or binning methods; investigation of linear and non-linear models for classification®ression ; identification of significant metabolites associated with disease; metabolic pathway

Reeder, Scott

Professor Radiology (608) 262-0135

My research interests focus on the development and validation of advanced magnetic resonance imaging (MRI) methods to quantify tissue characteristics such as tissue triglyceride and iron concentration. Our group also works to develop methods to quantify body composition, including visceral and subcutaneous adipose tissue volumes, total body fat and muscle volumes. Many of these methods can be performed in children and adults, as well as animal models such as mice, rats, and large animals.

Aceti, David

Researcher Biochemistry (608) 262-4687

Ligand screening to assign functions to orphan proteins

Ponik, Suzanne

Associate Scientist Cellular and Regenerative Biology (608) 265-5094

Increased collagen density and organization are driving factors for breast cancer progression. However, the specific cellular mechanisms resulting in altered cell metabolism, proliferation and invasion are not yet clearly defined. I am interested in identifying the mechanisms involved in altered cellular metabolism in a dense collagen microenvironment.

Stewart, Ron

Associate Director-Bioinformatics Morgridge Institute (608) 316-4349

We are interested in the relationship between metabolism and stem cell differentiation.

Bhute, Vijesh

Graduate Student Chemical and Biological Engineering (608) 556-8113

My research involves understanding the interactions of signaling pathways with metabolism. I primarily work with breast cancer cells and characterize the metabolic response of these cells to different small molecules and radiation. In collaboration with Department of Neurosurgery, I am also studying the impact of stroke in different tissues. I primarily use NMR based metabolomics as a tool for studying the metabolic responses.

Karasov, William

Professor Forest and Wildlife Ecology (608) 263-9319

We study metabolism of vertebrate wildlife. The majority of the studies involve measurement of whole-animal metabolism (indirect calorimetry), often using the doubly labeled water method. These measurements provide insights into nutrition, feeding and population ecology of wildlife and also their exposure to toxicants in foods. We also study digestive physiology, including work related to gut microbiome.

Roy, Sushmita

Assistant Professor Biostatistics and Medical Informatics (608) 316-4453

My research generally spans the development and application of computational methods based on machine learning for inference and analysis of different types of molecular regulatory networks. Specifically we are interested in developing methods that enable us to ask three main questions: (A) what networks exist in a specific biological context (e.g. a cell type, tissue, species), (B) how do they change between cell types and how do they evolve across species, and (C) how do changes in the network affect overall cellular and organismal state.

Bugni, Tim

Associate Professor Pharmaceutical Sciences Division (608) 263-2519

Bacteria produce a large repertoire of small molecules (<2,000 Da) that modulate a wide variety of biological targets. Many of these molecules have found therapeutic applications, especially in the areas of cancer and infectious disease. While genomic studies on bacteria have clearly shown that many more molecules remain undiscovered, finding new molecules has become akin to finding the needle in the haystack. We develop and apply LCMS-based metabolomics methods to greatly improve discovery rates by finding the needle in the haystack. We also use a combination of genomics and metabolomics to understand how bacterial interactions lead to production of new antibiotics. These strategies are yielding promising results in terms of generating new antifungal and antibiotic agents.

Arriola Apelo, Sebastian

Assistant Professor Dairy Science (608) 263-3490

The mechanistic Target of Rapamycin Complex 1 (mTORC1) is a central hub of nutritional and hormonal signals that regulates a wide range of metabolic processes, proteostasis among them. We study the role of mTORC1, on the regulation of protein synthesis, degradation and secretion in mammary epithelial cells, as mean of understanding milk protein production. We use nutritional, pharmacological and genetic approaches to quantitatively determine the response to different metabolic signals. The final objective is to determine accurate nutrient requirements for milk protein production and minimize the environmental impact of the dairy industry.

Attie, Alan

Professor Biochemistry (608) 262-1372

My lab studies pathways leading to metabolic diseases, especially diabetes and hyperlipidemia. We use genetics to discover novel genes and pathways leading to metabolic disease. For us, genetics provides a powerful means to establish causal connections and discover complex pathways. Much of our work on diabetes is focused on beta-cells, the cells in the endocrine pancreas that sense nutrients and secrete insulin. Our work has identified novel proteins involved in nutrient sensing, intracellular signaling, and vesicle trafficking.

Chang, Qiang

Associate Professor Medical Genetics and Neurology (608) 262-9416

My lab uses mouse models and human stem cell models to study neurodevelopmental disorders, including Rett syndrome (RTT). Recently, we have identified several mitochondrial defects in astrocytes differentiated from RTT patient-specific induced pluripotent stem cells (iPSCs). We are currently investigating the molecular and cellular events linking RTT mutations and mitochondrial dysfunction, and screening for drugs that reverse the mitochondrial defects in RTT.

Chung, Moo K.

Associate Professor Biostatistics (608) 217-2452

Methodological issues (computational, statistical, mathematical) on modeling PET scans of human brain at both the voxel-level and the network-level (metabolic connectivity).

Clagett-Dame, Margaret

Professor Biochemistry (608) 262-3450

Our metabolism work is focused on the absorption, distribution, metabolism and elimination of 2-methylene-19-nor vitamin D analogs that are active in skin. We administer radiolabeled compound to mice and evaluate total radioactivity over time in a variety of tissues, as well as the presence of intact compound and metabolites after extraction and separation by HPLC. Our goal is to use this information to better understand the biological activity and toxicity profile for these compounds.

Coon, Josh

Professor Chemistry and Biomolecular Chemistry (608) 263-1718

Our laboratory develops and applies mass spectrometric technology to study human health. We use these tools to answer fundamental questions in cell biology and to study human diseases including Alzheimer’s, diabetes, heart failure, cancer, obesity, asthma, among several others. The research team currently consists of twelve Ph.D. students, two postdoctoral fellows, two undergraduate researchers, and five staff scientists.

Craig, Betty

Professor Biochemistry (608) 263-7105

Our lab studies the roles of molecular chaperones in complex biological processes, ranging from general protein folding to propagation of yeast prions. We have a particular interest in mitochondrial physiology and metabolism, because - an Hsp70 molecular chaperone forms the core of the import motor required for translocation of proteins from the cytosol into the mitochondrial matrix; an Hsp70 is required for the biogenesis of Fe-S clusters, essential co-factors of a number of key metabolic enzymes and components of the respiratory chain.

Davis, Dawn Belt

Associate Professor Medicine/Endocrinology (608) 263-2443

The Davis lab is focused on pancreatic beta cell biology. We aim to understand how beta-cells adapt to nutritional and metabolic stressors in the setting of obesity and insulin resistance. The long term goal is to identify beneficial adaptations that can be harnessed to develop new therapeutic strategies for the prevention and treatment of diabetes. Dr. Davis also participates in collaborative clinical research to move bench science to human studies that can inform us on novel approaches to obesity and diabetes.

Gasch, Audrey

Professor of Genetics Laboratory of Genetics (608) 265-0859

Our lab combines functional omics, computational modeling, and molecular dissection to present a systems-wide view of how eukaryotic cells respond to environmental stress. Cellular response to acute stress often spans many levels of physiology and includes coordinated changes in transcription, translation, post-translational protein modification, proliferation, and metabolism. We are particularly interested in how cells reroute metabolic flux to support defense strategies, and how altered flux is regulated in response to stress and toxins.

Blum, Barak

Assistant Professor Cell and Regenerative Biology (608) 265-5211

Our research focuses on four main topics:
1) Pancreatic β cells maturation during development and their de-differentiation in diabetes
2) Organization of the islets of Langerhans into functional micro-organ units
3) Cellular ontogeny and cell identity of β cell maturation and de-differentiation
4) Genetic determinants behind the role of β cells in in type-1 diabetes

Greenspan, Daniel S

Professor Cell and Regenerative Biology (608) 262-4676

We have studied extracellular matrix components, growth factors, and metalloproteinases involved in controlling cell
behavior and involved in human disease. In recent work, we have found that a particular pericellular chain of
collagen V is important to the proper functioning of adipocytes and pancreatic beta cells (Huang et al, J Clin Invest
121, 769, 2001), and to the growth properties of cells, including breast cancer cells (Huang et al, Nature Comm 8,
DOI: 10.1038/ncomms14351, 2017). This collagen chain appears to work, at least in part, by affecting the ability of a
cell surface proteoglycan to act as a co-receptor for mitogenic growth factors. In addition to the above, a
spontaneous mutation in one of our mouse cell lines led to early embryonic lethality and has very recently led to our
ongoing characterization of a gene product that appears to control mitochondrial fusion, we think, by acting as a
GEF.

Ney, Denise M

Professor Nutritional Sciences (608) 262-4386

Dr. Ney uses preclinical mouse models and human subjects to investigate novel approaches to the management of PKU and obesity. The nutritional variable is a protein isolated from cheese whey, glycomacropeptide (GMP); GMP is a 64-amino acid glycophosphopeptide that does not contain aromatic amino acids. GMP is a prebiotic with beneficial effects on the intestinal microbiota, bone health and inflammation. It promotes satiety in humans. Studies are being conducted to investigate calcium homeostasis and the pathophysiology of skeletal fragility in human PKU and to determine the temporal relationships between changes in body composition and the intestinal microbiota.

Pike, J. Wesley

Professor of Biochemistry Biochemistry (608) 262-8229

Vitamin D, FGF23 and PTH represent endocrine hormones involved in the regulation of calcium and phosphate
metabolism in higher vertebrates. We are interested in the molecular mechanisms through which these hormones
control the regulation of mineral by the intestine, kidney and bone. These mechanisms involve control of gene
expression in each tissue as well as their actions in other tissues that also contribute to mineral and energy
homeostasis. Vitamin D is activated to a hormonal form via the expression of genes in the kidney that mediate this
activation. Thus, a recent focus has been on identifying the mechanisms through which the formation of the
hormonal form of vitamin D is controlled by these endocrine hormone such as FGF23 and PTH. Altered metabolism
of vitamin D during a wide variety of disease states impacts mineral metabolism directly, either causing diseases
such as cardiovascular calcification or exacerbating diseases such as chronic kidney syndromes and renal
osteodystrophy, among many other human maladies.

Roopra, Avtar

Associate Professor Neuroscience (608) 265-9072

Our early work demonstrated that REST is itself controlled by energy metabolism. Thus we were able to regulate a
suite of genes in a given cell type by simply controlling the amount of glucose supplied to the cells. Knowing that
REST regulates genes in the brain that are involved in epilepsy, we went on to demonstrate that epileptogenesis can
be retarded using a sugar 'mimic' 2-deoxyglucose (2DG), a well known anti-glycolytic compound. Since our study,
other groups have reproduced our results in other models of epilepsy (Garriga-Canut et al., 2006; Huang and
McNamara, 2006; Rho, 2008).
We demonstrated that the mechanism of this interaction depends upon binding of a REST co-repressor, CtBP. This
binding is sensitive to glycolytic activity, since CtBP is displaced from REST binding by the molecule, NADH,
generated by glycolysis. My lab is currently exploring how the other members of the REST-CtBP complex are
affected by metabolism: These other members include enzymes responsible for chromatin metabolism to impact
gene expression (Roopra et al., 2001; Roopra et al., 2004; Roopra et al., 2000). Chromatin and epigenetic modifiers
are of considerable clinical importance as drugs because of the potential to target their enzymatic function. Our
study will test whether chromatin regulators that are recruited with CtBP might be novel drug targets in the quest to
find ever more specific AEDs.
Metabolism and Plasticity
The degree to which REST represses gene expression is contingent on energy metabolism in the cell. My lab has
discovered that one set of genes controlled by REST modulates the mTOR pathway, a signaling cascade that is key
to learning, memory and epilepsy. During our studies of the role of REST in the long-term, chronic regulation of
mTOR pathway gene expression, we made another observation that has illustrated the role of a distinct energy
sensor, AMPK in rapid, acute responses. Thus we have shown that both Long Term Potentiation (LTP) and Long
Term Depression (LTD) in the hippocampus, both forms of mTOR dependent plasticity and are thought to play major
roles in memory and epilepsy, can be controlled through AMPK. Amongst other things, this result could explain why
humans and animals demonstrate enhanced learning and memory after glucose intake.

White, Heather

Assistant Professor Dairy Science (608) 263-7786

The transition to lactation period in dairy cattle represents the most critical time period for health and productivity. Dr.
White’s research program focuses on hepatic carbon flux during the transition to lactation, specifically as it relates to
gluconeogeneis and the TCA cycle, and the onset of metabolic disorders. Fundamental research on glucose and
energy metabolism leads to better understanding of the etiology, onset, progression, and genetic predisposition to
metabolic disorders, such as ketosis and fatty liver, in cattle and across species.

Kreeger, Pamela

Associate Professor BME, CRB (608) 890-2915

We are interested in multi-cellular interactions, with a focus on interactions between tumor and stromal cells in ovarian cancer. My lab uses a combination of engineered systems to study these interactions in vitro, experimental techniques, and computational models.

Ntambi, James M.

Professor Biochemistry (608) 265-3700

The general theme of my research is to understand the genetic regulation of metabolism, adipocyte biology and differentiation. I am specifically interested in lipid metabolism and the genetic basis of obesity, cardiovascular disease, insulin resistance and diabetes and how dietary factors, hormones and environmental factors influence these disease states. In particular I study the regulation of the mammalian stearoyl-CoA desaturase (SCD) genes that encode an enzyme involved in the biosynthesis of monounsaturated fatty acids. We are using these genes as a model to understand nutrient gene interactions.

Sauer, John-Demian (JD)

Assistant Professor Medical Microbiology and Immunology (608) 263-1529

Our lab studies host pathogen interactions using Listeria monocytogenes as a model pathogen. L. monocytogenes is an
intracellular pathogen that lives in the cytosol of host cells. In addition to being the cause of listeriosis, L. monocytogenes is
also being developed as a beneficial microbe for tumor immunotherapy. We are interested in mechanisms by which
bacteria adapt to their unique intracellular niche, but also the mechanisms by which host cells recognize infection and
respond appropriately. These adaptations by both the host, and the pathogen, dictate the outcome of infection as well as
the magnitude of the ensuing adaptive immune response. Not surprisingly, metabolic adaptations in the pathogen are
essential to cause disease, and likewise, metabolic perturbations are sensed by the host as a sign of infection. In addition,
nutritional immunity is a critical host defense against infection and modulation of immunometabolism is similarly a critical
determinant of robust cell-mediated immunity.

Schoeller, Dale

Director Isotope Ratio Mass Spectrometry Core Nutritional Sciences and Biotechnology Center (608) 262-1082

Our research focuses on energy metabolism with emphasis on human energy balance. We have expertise in stable isotope methods for energy expenditure using doubly labeled water and respiratory gas exchange; energy intake, substrate utilization using breath tests; and body composition using isotope dilution . We have studied environmental and behavior factors in the regulation of energy balance in obesity and wasting in clinical trials, population interventions and animal models. We also applied these methods to the validation of wearable monitors, survey tools and metabolic biomarkers. Human trials centered on the etiology, treatment, and prevention of obesity.

Skala, Melissa

Associate Professor Biomedical Engineering (608) 316-4108

We have developed label-free optical microscopy techniques to monitor metabolism in living samples on a single-cell level. Specifically, the auto-fluorescence of the metabolic co-enzymes NADH and FAD are imaged with two-photon microscopy in primary patient samples maintained in 3D organoids, and in mouse models in vivo. Our goal is to develop personalized screens for cancer treatment, and to understand interactions between the tumor cells and the tumor micro-environment. These microscopy tools are also used to study metabolic heterogeneity within tumor cells, immune cells, and fibroblasts, to guide the development of more effective cancer therapies.

Thomas, Michael G

Professor Bacteriology (608) 263-9075

My laboratory focuses on discoverying, deciphering, and directing natural product biosynthesis by bacteria. We use genome mining and metagenomics to discover new natural product biosynthesis potential, with a particular emphasis on nonribosomal peptides and polyketides. We use biochemical, genetic, structural biology, and molecular techniques to decipher how these molecules are assembled. We use directed evolution and chimeric enzyme construction to direct natural product biosynthesis to generate 'unnatural' derivatives of these metabolites. The combination of these areas of emphasis are targeting the development of the next generation of drugs.

Watters, Jyoti

Professor Comparative Biosciences (608) 262-1016

We are interested in understanding how paradigms of intermittent hypoxia (that mimic sleep apnea) cause epigenetic changes in central nervous system resident immune cells (microglia). In particular, we are investigating the roles of histone methylation and microRNAs in microglial inflammatory gene responses. Key microglial receptors and signaling pathways that are activated in response to intermittent hypoxia are a major focus. Since the prevalence of sleep apnea is increasing commensurate with the obesity epidemic, our studies also focus on how a high fat/high sugar diet influences the microglial immune response to intermittent hypoxia.

Anderson, Rozalyn

Associate Professor Medicine (608) 256-1901

My lab focuses on the role of metabolism in aging and age-related disease vulnerability. In addition to investigating the metabolism of normative aging in both mice and monkeys, we also study delayed aging by the dietary intervention of caloric restriction (CR), and use cell culture models to identify of processes and factors involved in the mechanisms of “anti-aging” by CR. Our studies suggest that age-associated changes in metabolic capacity are not just a biomarker of aging but may also be causally involved in creating increased disease vulnerability. The central hypothesis emerging from my work is that CR induces an active response involving a reprogramming of metabolism. A major current effort focuses on integrating transcriptional, proteomic, and metabolomic responses to CR, identifying differences in the response among tissues, and establishing how CR-induced changes metabolism intersect with delayed aging and increased resilience to age-related disease.