Rozalyn Anderson Dept. of Medicine, Division of Geriatrics & Adult Development
The primary focus of Dr. Anderson’s research is to identify critical factors involved in the mechanisms of aging retardation by caloric restriction. Despite the apparent phenotypic disparity across age-associated disorders such as cancer, cardiovascular disease, and diabetes, clues are emerging from the study of caloric restriction that may connect these disorders and illuminate the complexities of the aging process.
Sanjay Asthana Department of Medicine- Geriatrics
The major focus of Dr. Asthana’s research program is to evaluate the potential role of estrogen and related gonadal steroids on cognitive function and physical function skills of healthy older women as well as those with Alzheimer’s disease. His studies are designed to evaluate the therapeutic potential of estrogen and raloxifene for Alzheimer’s disease. He is also conducting research to determine if estrogen can improve cognitive changes associated with healthy aging.
Alan Attie Department of Biochemistry
Dr. Attie’s laboratory uses genetics to identify genes and pathways that contribute to type 2 diabetes. Current research includes studies of insulin processing and secretion, insulin degradation, beta-cell proliferation, and the effect of oxidative stress on signaling pathways. Additional genetic screens are aimed at finding genes involved in a broad range of metabolic disorders in addition to obesity and diabetes.
Tracy Baker-Herman Department of Comparative Biosciences
The Tracy Baker-Herman Lab studies homeostatic synaptic plasticity of respiratory motor output and its recovery following spinal injury. See her lab website.
Jill Barnes Dept. of Kinesiology
Barbara Bendlin Dept. of Medicine- Geriatrics & Adult Development
Dr. Bendlin’s work focuses on factors that contribute to or protect against the development of Alzheimer’s. Her recent work focuses on early brain changes in people who may go on to develop the disease, using MRI as a tool to understand the effect of risk factors (parental family history, genotype, Metabolic Syndrome) on brain blood flow and structure.
Corinna Burger Department of Neurology
The primary goal of my research program is to understand the molecular basis of cognition and aging. My early work identified Homer1c as one of the genes that is downregulated in aged rats that are learning-impaired in a spatial learning task compared to learning unimpaired aged animals. We have validated the role of this gene in learning at the functional level. First, we described for the first time the synaptic plasticity deficits of Homer1 knockout mice (H1-KO). Next, we introduced Homer1c into the hippocampus of Homer1 KO using Adeno-associated virus (rAAV) and for the first time we showed that gene targeting of Homer1c via rAAV was sufficient to rescue both the learning impairments and synaptic plasticity deficits of these animals. We are now elucidating the signaling cascades activated by Homer1c.
Cynthia Carlsson Department of Medicine- Geriatrics
Dr. Carlsson’s research focuses on the effects of vascular risk factors and their treatments on cognition and biomarkers for Alzheimer’s disease in persons at risk for dementia. Her recent work focuses on the effects of statin drugs on Alzheimer’s-related proteins found in the cerebrospinal fluid as well as the effects of these medications on MRI brain blood flow, arterial function, and cognition. See her website.
Ricki Colman Dept. of Cell and Regenerative Biology
Dr. Colman’s laboratory focuses on the relationships between aging, diet and energy metabolism in nonhuman primates. Since 1994 she has been studying the effects of long-term, moderate, adult-onset caloric restriction on aging in rhesus macaques. This ongoing study has proven that the positive effects of caloric restriction on healthspan and lifespan that were first identified in rodent models translate to a primate species. More recently, Dr. Colman has begun to develop a promising new small nonhuman primate model of aging and metabolism, the common marmoset. See her working group page.
Joshua Coon Dept. of Biomolecular Chemistry
My research group has the overarching goal of catalyzing evolution in the rapidly developing field of proteomics and to use these technologies to address fundamental problems in developmental biology. With emphasis on ion chemistry and instrumentation, we seek to develop and apply new enabling mass spectrometry-based (MS) proteomic technologies. These cutting-edge tools allow us to examine, with unprecedented chemical detail and sensitivity, the molecular events that commit human embryonic stem cells (hES cells) to exit the pluripotent state. Here we are focused on both intracellular signaling and the epigenetic regulation of pluripotency. For the former we ask which branches of the FGF signaling pathway are active in hES cells and which proteins/networks are phosphorylated upon differentiation. Epigenetics is believed to play a critical role in the establishment and maintenance of pluripotency; thus, we have also aimed our new technologies at interpreting the epigenetic codes and monitoring how these messages change during hES cell differentiation. See the Coon Laboratories website.
Dawn Belt Davis Department of Medicine- Endocrinology
Dr. Davis’ lab focuses diabetes risk in aging via an understanding of the regulation of pancreatic beta cell mass, which are endocrine cells that secrete insulin to regulate blood glucose levels.
John Denu Dept. of Biomolecular Chemistry
The Denu group investigates the molecular mechanisms and biological roles of reversible protein modification on gene expression and metabolism. They have demonstrated that Sirtuin protein deacetylases use NAD+ as a co-substrate and produce the novel metabolite acetyl-ADP-ribose. The group determined the catalytic mechanisms for three major families of histone acetyltransferases (HAT) and continue to investigate how chromatin binding proteins and modifying enzymes ‘read’ histone modifications and regulate gene expression. They provided the first evidence that mammalian metabolic enzymes are directly regulated by reversible acetylation. More recently, the Denu lab has revealed that major metabolic pathways are controlled by lysine acetylation. These studies have uncovered novel regulatory mechanisms in global metabolism, which have provided new insights into age-related diseases and cancer metabolism. The group has developed methods to quantify proteome-wide the acetylation stoichiometry at site-specific resolution, and a highly quantitative method to determine ~80 unique epigenetic states of chromatin from tissues and cells. A current major goal is to understand the link between metabolism and epigenetic mechanisms. In this effort, they recently reported that diet-gut microbiota interactions mediate host epigenetic programming in a variety of host tissues. See his website.
Corinne Engelman Department of Population Health Sciences
My research focuses on the study design and data analysis of genetic factors of complex diseases, including Alzheimer’s disease, using statistical and bioinformatic approaches for cleaning, processing, and analyzing large-scale genomic and other ‘omic’ data. My research program utilizes methodological approaches to examine joint effects of genetic and non-genetic factors, and gene-gene and gene-environment interactions. Findings from this research can be used to inform precision medicine.
Michael Fiore Department of Medicine- General Internal Medicine
Dr. Fiore founded, and has served as director of, the University of Wisconsin Center for Tobacco Research and Intervention since 1992. His chief research and policy focus has been to develop strategies to prompt clinicians and health care systems to intervene with patients who use tobacco and, currently, to optimize cessation treatments for all tobacco users. He and his Center colleagues have accomplished groundbreaking and internationally recognized research on the treatment of tobacco dependence. See his website.
Audrey Gasch Department of Genetics
Dr. Gasch’s work focuses on combining functional genomics and computational biology with traditional techniques in genetics and biochemistry to understand the role, regulation, and evolution of eukaryotic stress responses. A particular focus is elucidating signaling networks that control genomic expression in the model organism S. cerevisiae responding to diverse stresses. Many signaling proteins in this network are implicated in aging, cancer, and other human diseases, making this a useful model for human biology. See her lab website.
Pamela Herd Public Affairs and Dept. of Sociology
Pamela Herd’s research focuses on health, aging, stratification, and policy, with additional expertise in survey methods. She especially focuses on the relationship between socioeconomic status and health, with special attention to the relationship between education and health. She also have a growing portfolio of data collection and research in the area of biodemography, with the goal of understanding how social conditions “get under the skin” to influence health. Her expertise in survey research has led to her appointment as a member of the National Academy of Science Panel devoted to the future of NSF funded Surveys, as the Chair of the Board of Overseers for the General Social Survey and as a member of the Board of Overseers for the Panel Study of Income Dynamics. See her website.
Anna Huttenlocher Department of Pediatrics (Medical Microbiology & Immunology)
Dr. Huttenlocher’s research focuses on the basic mechanisms that regulate cell migration in processes such as tumor invasion and metastasis and the development of chronic inflammation. Her research team intends to identify novel regulators of these processes and define the relationships between these molecules and cell migration. See her lab website.
David Jarrard Department of Urology
Dr. Jarrard’s laboratory research is focused on the role of imprinting, or allele-specific expression, in aging and prostate cancer susceptibility. Mechanisms being examined for modulating the growth factor IGF-II imprint include DNA methylation. Models being utilized include human prostate cells and in a mouse model of aging.
Sterling Johnson Department of Medicine-Geriatrics
Dr. Johnson’s research employs functional neuroimaging techniques (such as fMRI and PET) and neuropsychological assessment to study the neurobiological and psychological processes that affect memory. A major focus of research is on people with genetic or cognitive risk factors for Alzheimer Disease to determine whether preclinical brain changes can be observed.
Michelle Kimple Department of Medicine- Endocrinology
Dr. Kimple leads a multi-level research team whose focus is on understanding how the beta-cells of the pancreas respond to nutrient and hormonal stimulation to affect biological changes. Her group is especially interested in elucidating how dysfunctional G protein-coupled receptor signaling pathways contribute to the pathogenesis of type 1 and type 2 diabetes and in translating these insights into new and improved diabetes therapeutics.
Dudley Lamming Dept. of Medicine- Endocrinology, Diabetes & Metabolism
The Lamming laboratory is focused on understanding the regulation of metabolic health and aging by dietary macronutrients and energy intake, with a particular emphasis on the mechanistic Target of Rapamycin (mTOR), an amino acid and insulin responsive protein kinase. Our recent studies have discovered that low protein diets promote metabolic health – improving blood sugar control and reducing adipose mass – in both humans and mice, and we have identified the dietary branched-chain amino acids leucine, isoleucine, and valine as key regulators of these effects. We are now focused on identifying the physiological and molecular mechanisms which mediate the beneficial impact of reduced dietary branched-chain amino acids, with a particular emphasis on the understanding the role of mTOR signaling. We are also testing if mTOR inhibitors or diets with altered macronutrient content can be used as interventions in metabolic and age-related diseases including diabetes, cancer, and Hutchinson-Gilford Progeria Syndrome.
Joshua Lang Department of Medicine- Hematology/Oncology
My laboratory has two main focus areas: 1) Biomarker development and 2) Improving immune recognition of tumor cells. Our research in biomarkers involves engineering and assay development for predictive and pharmacodynamic targets of anti-cancer therapies. These biomarkers identify molecular signatures of therapeutic resistance that evolve over the course of treatment. These assays include single cell analysis of tumor heterogeneity at the protein, transcriptomic and genomic levels. Our research in tumor immunology involves the pre-clinical and clinical development of therapeutic strategies combining anti-tumor immunotherapies with epigenetic modifying agents. This work integrates patient specific biomarkers to develop personalized therapeutic strategies for patients with cancer. We have ongoing projects in prostate, renal, breast, lung, pancreas, and colorectal cancer. See his website.
Wan-ju Li Dept. of Orthopedics and Rehabilitation
My research focuses on stem cells in skeletal biology and regeneration to develop therapies for orthopedic applications. Particularly, I am interested in physiology of skeletal stem cells during degenerative diseases, such as osteoarthritis and osteoporosis. I also work on developing tissue engineering strategies to enhance cartilage and bone regeneration with focuses on environmental cues and differentiation of induced pluripotent stem cells. See his website.
Matthew Merrins Dept. of Medicine- Endocrinology, Diabetes & Metabolism; Dept. of Biomolecular Chemistry
Dr. Merrins’ laboratory studies the metabolic control of insulin secretion from pancreatic beta cells. His current work centers on 1) control of insulin secretion by glycolytic pyruvate kinases, and 2) the regulation of mitochondrial metabolism by cyclin-dependent kinases. A central focus of the laboratory is the use of fluorescence microscopy to monitor biochemical reactions as they occur in living cells. Living islet tissue from mice and humans is used in combination with biochemistry and patch-clamp electrophysiology to study how metabolic signaling responds to the challenges of overnutrition, aging, and diabetes.
Darcie Moore Dept. of Neuroscience
Stem cell compartments undergo dysfunction with age, ultimately contributing to greater organismal aging. Understanding how and why these stem cells age is a main focus of our lab. Young mammalian neural stem cells can segregate specific cargoes during mitosis between daughter cells resulting in an asymmetric inheritance of potential “aging factors,” with downstream functional consequences for each daughter. In neural stem cells from old animals, this segregation becomes more symmetric. We are investigating the mechanisms that create and maintain this segregation, and identifying what changes with age. Additionally, we are interested in discovering what cargoes are segregated and the cost of this segregation.
Dr. Moore is one of the recipients of the 2018 NIH New Innovator Award.
David Pagliarini Department of Biochemistry
Dr. Pagliarini’s lab focuses on the biochemical underpinnings of mitochondrial dysfunction in aging and age-related diseases. Mitochondrial dysfunction underlies more than 50 inborn errors of metabolism, and strongly contributes to a growing list of common metabolic and neurodegenerative disorders including type II diabetes, Parkinson’s disease, Alzheimer’s disease, and various forms of cancer.
Tomas Prolla Department of Genetics
Dr. Prolla’s laboratory focuses on understanding the molecular basis of the aging process and common age-related human diseases through the use of large-scale gene expression analysis. This work has developed hundreds of biomarkers to measure the aging process in genetically altered mice.
Luigi Puglielli Dept. of Medicine- Geriatrics
Dr. Puglielli’s research interests focus on the molecular mechanisms that are responsible for the cognitive loss that accompanies aging and the neurodegeneration that characterizes Alzheimer’s disease. His research uses multidisciplinary approaches on in vitro, ex vivo and in vivo models. Such approaches include biochemical, cellular and molecular techniques, as well as electrophysiological, cognitive/behavioral, and structural analysis.
Federico Rey Dept. of Bacteriology
We are seeking to understand how environment and host genetics affect organismal and functional microbial representation in the distal gut and to understand how diet-microbe interactions impact metabolic and cardiovascular diseases. Towards this end, we are using a combination of human studies, gnotobiotic mouse models of cardiovascular disease, bacterial genetics, transcriptional profiling and metabolomics. See his website.
Subhojit Roy Dept. of Pathology & Laboratory Medicine
I am a physician-scientist, trained in Neuropathology and cellular/molecular neuroscience. My lab is generally interested in neuronal trafficking in physiology and disease. Specifically, we are interested in normal axonal transport mechanisms as it relates to axonal/synaptic homeostasis; and physiologic and pathologic trafficking pathways in Alzheimer’s and Parkinson’s disease. Our approach is to develop high-fidelity neuronal model-systems that accurately capture key aspects of pathophysiology, generate predictions using these systems, and then ask focused questions in mouse-models and human brains. So far this approach has been fruitful, allowing us to uncover new aspects of alpha-synuclein and amyloid pathobiology. As a Neuropathologist, I am involved in clinical and autopsy service, and the Neuropathology core leader of the Wisconsin Alzheimer Center. In this capacity, I also perform translational research with other neuroscientists. See his website.
Carol Ryff Department of Psychology
Dr. Ryff’s research addresses aging as a multidisciplinary challenge that requires integration of many levels of analysis: sociodemographic characteristics, psychosocial resources, life stresses, health behaviors and practices, neurobiological risk and protective factors, and health outcomes (mental and physical). We study the pathways through which these influences come together in longitudinal investigations, involving local, state, and national samples.
Miriam Shelef Dept. of Medicine- Rheumatology
Dr. Shelef is an immunologist and a rheumatologist with a research program focused on better understanding the pathophysiology of rheumatoid arthritis to inform the development of novel biomarkers and treatments. Her research currently aims to (1) define the role of citrullination and the citrullinating enzymes in immunity, inflammation, and arthritis, (2) determine how genetic variants associated with rheumatoid arthritis cause dysregulation of the immune system, and (3) identify novel autoantibodies in rheumatoid arthritis and related diseases which can ultimately serve as diagnostic tools. See her website.
Vikas Sing Dept. of Biostatistics
Dr. Singh’s group focuses on the design of novel AI algorithms for image analysis motivated by applications in aging/Alzheimer’s disease studies. See his website.
Darryl Thelen College of Engineering
Dr. Thelen’s Neuromuscular Biomechanics Lab studies the effects of aging and injury on the neuromusculoskeletal system, including using quantitative ultrasonic imaging to measure tendon stiffness in older adults to understand soft tissue injuries, and using neuromodulation and exercise to enhance balance.
David Wassarman Dept. of Medical Genetics
We are interested in understanding how the brain contributes to gradual functional decline and increased disease risk with age. We believe that our recent discovery that death following traumatic brain injury (TBI) is preceded by physiological events that also precede death from normal aging in Drosophila melanogaster can be exploited to address complex aging problems and, thereby, help meet the healthcare needs of an aging human population. Thus, we are using genetic and molecular approaches in Drosophila to characterize the physiological events shared by TBI and aging: altered energy metabolism, prolonged activation of the innate immune response, and intestinal epithelial barrier permeability. See his website.