Faculty Mentors

Photo of Roz Anderson

Rozalyn Anderson, PhD

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Dr. Anderson is a leader in the field of caloric restriction (CR) research with a special focus on metabolic regulators underlying beneficial effects of CR on longevity and age associated diseases. Her current studies are investigating the role of mitochondrial energy metabolism in the mechanisms of CR, including the cellular and molecular impact of CR on skeletal muscle, liver, brain, and white adipose tissue metabolism and function. Findings from her studies have suggested that PGC-1α is a critical regulator of mitochondria and that adipokines and lipokines regulated by PGC-1a may contribute to CR induced differences in metabolic homeostasis and inflammation.

Current Funding: R56 (PI), NIA RO1 (MPI), NIH UL1 (PI), Glenn Foundation grant (PI), American Foundation for Aging Research grant (PI)

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Director wearing a suit.Sanjay Asthana, MD

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The major focus of Dr. Asthana’s clinical research program is on the neuroendocrinology and preclinical biomarkers of Alzheimer’s disease (AD). He has pioneered prospective evaluation of the potential beneficial effects of estrogen and related gonadal steroids on cognitive function and mood in healthy recently menopausal and older postmenopausal women with AD. Results of his studies have shown that short-term therapy with transdermal estradiol enhanced verbal memory and attention in older women with AD, and that extended therapy with oral conjugated equine estrogen (CEE) in recently menopausal women improves mood, but does not enhance cognition. Importantly, unlike the Women’s Health Initiative, findings from Dr.Asthana’s studies did not demonstrate any adverse cognitive effects in healthy peri-menopausal women. Notably, these findings are considered to be of major clinical significance. More recently, as Director of the Wisconsin ADRC, Dr. Asthana oversees a large research program focused on identifying preclinical biomarkers of AD in at-risk populations.

Current Funding: NIA P30 (PI), NIA P50 (PI), NIA T32 (PI), NIA U01 (Site PI), NIA R01 (MPI)

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Picture of T32 Mentor Alan AttieAlan Attie, PhD

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The major focus of Dr. Attie’s research relates to the genetics of diabetes and obesity in mice. He has mapped three gene loci for diabetes and two for obesity in mice. Additionally, he is using powerful tools of mouse genetics to positionally clone the remaining genes and to study the biochemistry of these traits in congenic mouse strains. Dr. Attie has also carried out extensive expression profiling work to study the changes in gene expression found in obesity and diabetes.

Current Funding: 2 RO1s (PI), RO1 (Co-I), Juvenile Diabetes Research Foundation grant (PI);

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Picture of T32 Mentor Tracy Baker-HermanTracy Baker, PhD

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The major focus of Dr. Baker’s research is on the mechanisms of plasticity in the respiratory control system. Specifically, her studies examine how respiratory motor neurons adjust to persistent changes in descending drive from brainstem to achieve optimal ventilation. Some of her ongoing studies evaluate the role of glial-derived TNFα and retinoic acid in homeostatic regulation of respiratory motor unit, while others are examining recovery of respiratory motor output following spinal injury. The applications of Dr. Baker-Herman research involve discovery of potential therapeutic targets to restore ventilation when endogenous mechanisms of plasticity are insufficient.

Current Funding: RO1 (PI), RO1 (Co-I)

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Mentor Dr. Jill BarnesJill Barnes, PhD

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Summary: The primary focus of Dr. Barnes’ research is to understand the effect of aging on blood flow regulation in humans and how this relates to the risk of cardiovascular disease and dementia.  Dr. Barnes is specifically interested in how age-associated changes in the structure and function of blood vessels and sympathetic nervous system activity influence the control of blood flow to the brain. In addition, her research focuses on how lifestyle modifications may prevent, and how chronic diseases accelerate, these negative consequences of aging on brain blood flow regulation.

Current Funding: 1 RF1 (PI), 1 DOD grant (PI), 1 R00 (PI),1 Alzheimer’s Association Grant (PI), 1 American Heart Association Grant (PI)

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Picture of T32 Mentor Barbara BendlinBarbara Bendlin, PhD

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The focus of research in Dr. Bendlin’s lab relates to identifying neuroimaging biomarkers of preclinical stages of Alzheimer’s disease (AD) and insulin resistance (IR) and the risk of AD. She utilizes MRI and PET brain imaging to study the structure, function and blood flow to the brain and relates these findings to AD biomarkers in the cerebrospinal fluid (CSF). Additional studies in her lab focus on characterizing AD risk in persons with IR. Findings from her studies have suggested reduced blood flow and decreased WM volume in participants with a parental history of AD, and increased amyloid deposition and early cognitive changes in people with IR. Importantly these changes correlate directly with CSF biomarkers of preclinical AD. Additional findings from her studies have indicated that subjects using non-steroidal anti-inflammatory drugs (NSAIDs) maintain their WM structure and function.

Current Funding: RO1 (PI), NIA UO1 (MPI), NIA R56 (MPI), NIA P50 (Sub PI and Co-I), R21 (MPI), 2 RO1s (Co-I), U54 (Co-I)

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Picture of T32 Mentor Corinna BurgerCorinna Burger, PhD

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Dr. Burger’s research targets study of the molecular and cellular mechanisms of learning and memory in aging and gene-therapy for neurodegenerative diseases. To that end, she uses viral gene delivery to study cognition and creates animal models to evaluate gene therapies for Parkinson’s disease (PD). Her recent studies have focused on the potential role of Homer1c gene in aging-associated cognitive changes, evaluated the therapeutic efficacy of glial-derived neurotrophic factor (GDNF) for PD and developed and optimized vectors for gene expression in the nervous system. Additional studies in her lab focus on the role of viral gene transfer in brain circuitry, signaling cascades and timing of protein expression.

Current Funding: NIA RO1 (PI)

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Picture of T32 Mentor Cynthia CarlssonCynthia Carlsson, MD, MS

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Dr. Carlsson is a fellowship trained geriatrician with a major research interest in vascular dementia and cerebrospinal fluid (CSF) biomarkers of preclinical stages of Alzheimer’s disease. Additionally, she is investigating the potential of statin drugs to prevent AD. Findings from her studies have indicated that short-term therapy with statins increases cerebral blood flow in healthy middle-aged adults at risk for AD, and that there is a direct relationship between plasma levels of cholesterol and CSF measures of amyloid precursor protein (APP) metabolism. Another area of Dr. Carlsson’s research interest relates to clinical trials in persons at risk for AD. She is currently conducting a VA-funded (Merit Review grant) clinical trial of fish oil in middle aged Veterans.

Current Funding: Merit Review (VA grant), NIA P50 (Core Leader), 3 NIA/ADCS grants (Site PI), 2 RO1s (Co-I)

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Picture of T32 Mentor Ricki ColmanRicki Colman, PhD

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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.

Current Funding: RO1 (PI), R24 (PI), R21 (PI)

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Picture of T32 Mentor Joshua CoonJoshua Coon, PhD

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Dr. Coon is the director of The National Center for Quantitative Biology of Complex Systems — an NIH Biotechnology Research Resource — where his group is developing next-generation protein measurement technologies for a wide variety of biomedical applications. These technologies are focused on making whole proteome analysis faster and more broadly accessible in order to answer fundamental questions in human diseases such as Alzheimer’s, diabetes, heart failure, cancer, obesity, asthma, among several others.  Additional resources in his lab include recent advances in informatics, including molecular identification, quantification and data visualization that allows rapid data analysis and procurement of biological insights.

Current Funding: P41 (PI), R35 (PI)

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Picture of T32 Mentor Dawn Belt-DavisDawn Belt Davis, MD, PhD

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Dr. Davis’s lab focuses on the pancreatic cell biology and its role in the pathogenesis of diabetes mellitus. For the first time, her studies have identified a transcription factor called Tcf19 that is necessary for beta cell proliferation and protect them from apoptosis. Tcf19 has recently been associated with type 1 and type 2 diabetes mellitus and a better understanding of molecular mechanisms underlying its role in diabetes could have major therapeutic implications. Ongoing studies in this area involves molecular and cellular studies in gene transcription, cell cycle regulation and pro-survival pathways. The second area of research in Dr. Davis’s lab focuses on the potential mechanisms underlying protective effects of cholecystokinin (CCK) on pancreatic beta-cell apoptosis. Current research in this area has identified that the expression of CCK is regulated by another key hormone, glucagon-like peptide-1 (GLP-1) in a novel intra-islet incretin network that protects beta-cells from apoptosis. Overall Dr. Davis’s research has major implications for the treatment of diabetes mellitus.

Current Funding: RO1 (PI), Merit Review from VA (PI)

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Picture of T32 Mentor Dustin DemingDustin Deming, MD

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Dr. Dustin Deming is a faculty member in the Division of Hematology, Medical Oncology and Palliative Care. As clinician, his primary focus is on medical care of patients living with gastrointestinal cancers including colorectal cancer and esophageal cancer. He serves as Clinical Co-Chair of the UW Carbone Cancer Center (UW CCC) Molecular Tumor Board, as Director and Founder of the UW CCC Colorectal and Anal Cancer Working Group (CRAWG), as Vice Chair of the Chemotherapy Council, and as Medical Director of the William S. Middleton Memorial Hospital Oncology Infusion Clinic. As a physician-scientist, Dr. Deming’s research program focuses on developing precision medicine treatments for different subtypes of colon cancer. As a medical educator, he provides classroom and clinical instruction to medical students, residents, fellows, and other oncology providers.

Current Funding: R37 (PI), RO1 (Subcontract PI)

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Picture of T32 Mentor John DenuJohn Denu, MD, PhD

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The overarching scientific theme of Dr. Denu’s research program is epigenetics of aging and related diseases. His laboratory investigates the mechanisms and biological function of reversible protein modifications involved in modulating signal transduction, chromatin dynamics and gene activation. One special focus of his ongoing studies is on understanding the major enzyme families that catalyze histone acetylation. Another area of his research interest relates to sirtuins and reversible enzyme acetylation. Sirtuins are a conserved family of NAD+ dependent protein deacetylases that play an important role in protein acetylation. Dr. Denu’s lab is currently focusing on the hypothesis that reversible protein acetylation is a major regulatory mechanism for controlling metabolic processes that underlie several common aging-related diseases.

Current Funding: R37 (PI), RO1 (PI), RO3 (PI), RO1 (Co-I), NHLBI grant (Sub-PI), Wisconsin Alumni Research Foundation (WARF) grant (PI), American Society for Biochemistry and Molecular Biology grant (PI)

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Picture of T32 Mentor Corinne EngelmanCorinne Engelman, PhD

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The major focus of Dr. Engelman’s research relates to the genetic epidemiology of Alzheimer’s disease (AD) and vitamin D. Her recent AD-related research has utilized longitudinal data from the renowned Wisconsin Registry for Alzheimer’s Prevention (WRAP) and underscored the gene-gene and gene-environment interactions in four major pathways relevant to cognition and AD risk: cholesterol metabolism, insulin resistance, inflammation and vitamin D metabolism. These studies have identified new genes and their potential effects on the neurobiology of AD. The vitamin D focused research evaluates the genetic and non-genetic factors associated with vitamin D as it relates to major aging-associated diseases, including AD, cancer, diabetes and heart disease. Dr. Engelman investigates the genetics of these diseases utilizing data from the Survey of the Health of Wisconsin (SHOW).

Current Funding: NIA RO1 (PI), R56 (PI), 2 RO1s (Co-I), 2 State of Wisconsin (Wisconsin Partnership Program) grants (PI)

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Picture of T32 Mentor Michael FioreMichael Fiore, MD, MPH, MBA

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Michael Fiore, MD, MPH, MBA, University of Wisconsin Hilldale Professor of Medicine, founded and has served as Director of the University of Wisconsin Center for Tobacco Research and Intervention (UW-CTRI) since 1992. He is a clinically active general internist and preventive medicine specialist, treating patients for tobacco dependence. Dr. Fiore is a nationally recognized expert on how to help patients quit smoking, providing perspectives to audiences ranging from Good Morning America to the United States Senate. He has written more than 250 articles, chapters, and books on cigarette smoking and contributed to U.S. Surgeon General Reports in 2000 and 2020. He served as chair of the national panels that produced all three editions (1996, 2000, 2008) of the United States Public Health Services Clinical Practice Guideline, Treating Tobacco Use and Dependence. He is a member of the National Academy of Medicine

Current Funding: R35 (PI), PO1 (MPI), 2 RO1s (MPI), RO1 (Co-I), 2 State of Wisconsin Grants (PI), UW CTSA grant (PI)

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Picture of T32 Mentor Audrey GaschAudrey Gasch, PhD

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The major focus of Dr. Gasch’s research relates to the study of molecular mechanisms underlying response to environmental stress. Using DNA microarrays, she has identified a large gene expression program in yeast, called the environmental stress response (ESR) that is activated by many types of stress. Her studies that combine comparative and functional genomics, computational and systems biology have shown that ESR is governed by many different transcription factors, RNA binding proteins and upstream signaling pathways. Results from these studies will reveal important information concerning genetic mechanisms mediating response to stress.

Current Funding: RO1 (PI), NIGMS T32 (PI)

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Picture of T32 Mentor Anna HuttenlocherAnna Huttenlocher, PhD

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Dr. Huttenlocher´s research focuses on understanding the cellular and molecular mechanisms that regulate cell migration in the context of wound healing, inflammation and cancer. Her lab uses state-of-the-art imaging, molecular tools and photomanipulation to examine innate immune function in health and disease.

Current Funding: R35 (PI), RO1 (PI), NIGMS T32 (PI)

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Picture of T32 Mentor David JarrardDavid Jarrard, MD

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Dr. Jarrard’s research is focused on two areas: 1) the role of epigenetics in aging and prostate cancer susceptibility, and 2) the molecular pathways involved in the bypass of senescence. He is currently investigating alterations in imprinting in both an in vitro human prostate epithelial cell model and in vivo mouse model of aging. Based on his observation that the peripheral zone of the prostate from men with prostate cancer commonly contains biallelic IGF2 expression, he hypothesized that a loss of imprinting in IGF2, an oncogenic growth factor, contributes to the development of prostate cancer with aging.

Current Funding: RO1 (MPI), 4 DOD grants (PI), P30 (Co-I), RO1 (Co-I)

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Picture of T32 Mentor Sterling JohnsonSterling Johnson, PhD

WRAP; Brain Map

Dr. Johnson leads the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and is associate director of the Wisconsin Alzheimer’s Institute and the Wisconsin Alzheimer’s Disease Research Center in which he also leads the Biomarker Core. His research program uses amyloid and tau PET neuroimaging, CSF and cognitive measures to identify Alzheimer’s disease (AD) as early as possible. The WRAP study is a major longitudinal observational risk-enriched cohort that examines biomarker and cognitive change from midlife. Together with several WRAP investigators and other experts across campus he examines the role of vascular health factors and vascular imaging, lifestyle and genetics to understand their contribution, if any, to the temporal progression of AD through its pre-symptomatic and clinical stages. Alzheimer’s disease is a chronic disease of aging with a prolonged preclinical course. The gap between onset of the disease and its eventual manifestation in symptoms can vary widely from person to person and this is problem is of particular focus.

Recent discoveries have A) characterized the rate of amyloid accumulation among people who are amyloid positive, revealing striking uniformity from person to person; B) demonstrated that the age of onset of amyloid pathology and thereby its chronicity or duration can be estimated from a single amyloid scan measurement; C) shown that health and lifestyle factors do not necessarily effect amyloid accumulation but do affect brain health; D) uncovered new ways of detecting early cognitive decline—prior to the stage of mild cognitive impairment.  Dr. Johnson has over 285 publications and has been continuously funded by the NIH for over 20 years.

Current Funding: 2 RO1s (PI), RO1 (MPI), 2 R01s (site PI), U19 ADNI study (Site PI), NIA P30 Alzheimer’s Disease Research Center (Associate Director and Core-Leader)

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Picture of T32 Mentor Tim KampTimothy Kamp, MD, PhD

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The primary focus of Dr. Kamp’s research program is on embryonic stem cells (ESCs) and their applications to cardiovascular research and cardioregenerative medicine. His research suggests that human ESCs (hESCs) differentiate in embryoid bodies to form spontaneously contracting cardiomyocytes. Moreover, electrophysiological studies indicate that hESCs differentiate into different types of cardiac cells, including atrial, nodal and ventricular. Ongoing research in Dr. Kamp’s lab is focused on understanding cardiogenesis in the ES cell system and innovative ways to obtain defined populations of hESC-derived cardiomyocytes. Other ongoing projects involve identification of optimal cellular populations derived from ESCs for cardiac therapy, determining the best delivery strategies and overcoming challenges related to immune rejection of allogenic cells.

Current Funding: RO1 (PI), NIH UAB (MPI), RO1 (Co-I), Wisconsin Alumni Research Foundation (WARF) grant (PI)

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T32 mentor: Dr. Keck

James Keck, PhD

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Research in the Keck lab examines the structural mechanisms that drive DNA replication, replication restart, recombination, and repair reactions. Successful execution of these pathways is essential in all cells, and defects in the proteins that facilitate genome maintenance reactions lead to genome instability, premature

aging, cell death, and disease. Our studies combine structural approaches with biochemical, genetic, and cellular biology methods to answer fundamental questions in genome biology.

Current Funding: R01 (MPI), R01 (MPI), RM1 (MPI), Kellett mid-career award, Shaw scientist award

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Picture of T32 Mentor Nancy KellerNancy Keller, PhD

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My research focus lies in genetically dissecting those aspects of Aspergillus spp. that render them potent pathogens and superb natural product machines. We are interested in elucidating the mechanism of fungal sporulation and host/pathogen interactions; processes intimately linked to secondary metabolite (e.g. mycotoxin) production. My tactic has been to use the genetic model Aspergillus nidulans to elucidate important biological processes in this genus and then carry this information to the plant pathogen A. flavus and the human pathogen A. fumigatus. The former two pathogen contaminates seed crops worldwide with aflatoxin, the most potent naturally occurring carcinogen known. The latter pathogen is now tied with Candida as the most serious human mycopathogen in developed countries where it can cause invasive aspergillosis, a disease with a mortality rate ranging from 50 to 90%.

Current Funding: HATCH-USDA (PI), US-Israel Binational Agricultural Research & Development Fund (MPI), NCCIH R44 (Co-I), USDA (Co-I), NIAID R44 (MPI)

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Picture of T32 Mentor Michelle KimpleMichelle Kimple, PhD

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The major objective of Dr. Kimple’s research program is on G-proteins and their potential role in the regulation of insulin secretion. Her studies focus on G-protein signaling pathways in regulating β-cell decompensation. Recent findings from these studies have suggested that the α-subunit of the heterotrimeric Gz protein, Gα (z), impairs insulin secretion by suppressing production of cAMP. Further, mice genetically deficient for Gα (z) are protected from developing glucose intolerance when fed a high-fat diet. These results suggest a potential role of Gα (z) in β-cell function.

Current Funding: RO1 (PI)

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Picture of T32 Mentor Dudley LammingDudley Lamming, PhD

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The goal of Dr. Lamming’s research program is to understand how nutrient responsive signaling pathways can be harnessed to promote health and longevity. His studies primarily focus on the physiological role played by the mechanistic target of rapamycin (mTOR), a protein kinase that regulates complex cellular processes, including growth, metabolism and aging. Recent findings from his program have shown that rapamycin, an inhibitor of mTOR signaling can improve both longevity and health in model organisms, including mammals. Additional findings from Dr. Lamming’s studies have revealed that decreased consumption of branched chain amino acids improves metabolic health and that reduction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model.

Current Funding:  R01 (PI), R01 (MPI), R21 (MPI), UW2020 (PI)

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Picture of T32 Mentor Joshua LangJoshua Lang, MD, MS

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Dr. Lang’s research program broadly investigates mechanisms of immune evasion and therapeutic resistance in cancer, with a particular focus in diseases of the elderly such as prostate cancer. However, given the scarcity of patient tissue, his lab collaborates with biomedical engineering to develop novel microfluidic technologies to perform comprehensive molecular analysis of tumor cells from a simple patient blood sample.

These technologies allow capture of circulating tumor cells for protein, gene expression and genomic studies down to the single cell level. Results of these studies have identified a range of molecular alterations in prostate cancer that develop over the course of therapy to impair immune recognition. These changes are mediated, in part, by an accumulation of epigenetic alterations that promote immune evasion. Dr. Lang’s lab has adapted new microfluidic technologies to evaluate epigenetic changes at the single cell level that regulate immune effector molecules, which may be promoted during aging. It is projected that a better understanding of the epigenetic and molecular mechanisms will lead to more effective treatments for prostate cancer.

Current Funding: RO1 (MPI), 3 DOD grants (PI), 2 PCF grants (PI), 2 DOD grants (Co-I), VFCR grant (Co-I), NIGM grant (Sub PI)

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Picture of T32 Mentor Wan-Ju LiWan-Ju Li, PhD, MS

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My research goal is to investigate and develop stem cell-based approaches to regenerate skeletal tissues, cartilage and bone, for orthopedic applications. We focus on solving two unmet challenges: 1) impact of cellular senescence associated with donor age and in vitro culture on lineage differentiation of stem cells and 2) controlled chondrogenic differentiation of stem cells into functional hyaline chondrocytes/cartilage. Our group uses induced pluripotent stem cells (iPSCs) created through direct reprogramming of somatic cells by the integration-free episomal approach to address these challenges. Our research strategies and directions are promising because we have demonstrated that cellular reprogramming rejuvenates mesenchymal stem cells to enhance their properties for skeletal regeneration, and iPSCs are systemically induced into functional chondrocytes for hyaline cartilage formation.

Current Funding: RO1 (PI)

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Picture of T32 Mentor Matt MerrinsMatthew J. Merrins, Ph.D

Medicine Website

Biomolecular Chemistry Website

Merrins Lab

Research in our laboratory focuses on metabolic signaling in the pancreatic islets of Langerhans. As metabolic sensors for the organism, islets regulate blood glucose by releasing the hormones insulin and glucagon. Our main interests lie in two features of nutrient metabolism in islet cells, (1) the ability to trigger pulses of insulin release, and (2) the ability to fine-tune hormone secretion through cell-cell communication. To understand how these processes adapt to environmental stress, we utilize mouse models of obesity/diabetes in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (3D light-sheet imaging, optogenetics, and 2-photon microscopy) to monitor biochemical reactions as they occur in living cells.

Current Funding: NIDDK RO1 (PI), NIA R01 (MPI)

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Picture of T32 Mentor Darcie MooreDarcie Moore, PhD

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The primary research focus of Dr. Moore’s lab is on neural stem cells and aging. Recent evidence from her lab has shown that neural stem cells (NSCs) asymmetrically segregate cargoes (i.e., damaged proteins) when they divide, leaving one daughter cell more “clean” than the other. Additionally, her studies have identified a diffusion barrier in the endoplasmic reticulum membrane in dividing NSCs that may limit the movement of cargoes. Notably this diffusion barrier weakens with aging. Ongoing studies in Dr. Moore’s program targets mechanisms used by stem cells to create the symmetric segregation of cargoes to identify what other components are segregated, and to use this knowledge to improve stem cell aging. Her lab uses mammalian embryonic stem cells and adult neural stem cells as model systems. Current studies use advanced live imaging techniques, including FLIP, FRAP, photoactivation, 4D timelapse and computer learning-based high-throughput imaging to investigate cargoes in mitotic stem cells.

Current Funding: DP2 (PI), Shaw Scientist Award (PI), NINDS R21 (PI)

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Ozioma Okonkwo, PhD

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Dr. Okonkwo’s research focuses on clarifying how alterations in the brain and other biomolecules (such as cerebrospinal fluid β-amyloid) place some cognitively-normal individuals on a pernicious trajectory that culminates in Alzheimer’s dementia. In this context, he is also interested in discovering new knowledge concerning the modulation of the link between brain changes and cognitive decline by both modifiable factors like cognitively-stimulating activities or physical exercise and non-modifiable factors such as genetic vulnerability.

Current Funding: 1 NIA R01 (PI), 4 NIA R01 (Co-I), 2 NIA RF1 (Co-I), 3 U19 (Core Lead/Site PI), 1 NIA R21 (Co-I), and 4 Foundation grants

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Picture of T32 Mentor Tomas ProllaTomas Prolla, PhD

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Dr. Prolla’s laboratory is focused on understanding the role of eukaryotic DNA repair pathways in aging and cancer. The primary experimental approach in his lab is the use of gene targeting in embryonic stem cells to discover gene function and to generate mouse models of human diseases. The most recent work involves the DNA mismatch repair genes Msh2, MIh1, Pms2 and Pms1. Notably mutations in these genes result in hereditary colon cancer, the most common human inherited cancer. Additional projects in Dr. Prolla’s lab involve study of the effect of specific DNA lesions on aging parameters, by generating mice deficient for a variety of DNA repair enzymes. The goal with these experiments is to determine the relevance of different DNA repair pathways to cancer and aging.

Current Funding: 2 RO1s (PI), Glenn Foundation Award (PI), pharma grant (PI)

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Picture of T32 Mentor Luigi PuglielliLuigi Puglielli, MD, PhD

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Dr. Puglielli’s research interests focus on elucidating the molecular mechanisms of neurodegeneration and neurodevelopment. The Puglielli laboratory employs a combination of biochemical, cellular, molecular, and genetic approaches in in vitro, ex vivo and in vivo models. In 2007 the Puglielli laboratory reported that nascent proteins could undergo Nε-lysine acetylation in the lumen of the endoplasmic reticulum (ER). This discovery resulted in the identification of a previously unknown biochemical machinery that impacts on the biology of the ER. Specifically, ER-based acetylation maintains proteostasis within the ER and secretory pathway by regulating (i) selection of correctly folded polypeptides though quality control and (ii) reticulophagy-mediated disposal of toxic protein aggregates. Ultimately, these two functions ensure the efficiency of the secretory pathway. Dr. Puglielli’s recent studies have shown that a dysfunctional ER acetylation machinery is linked to different human diseases across lifespan, from developmental delay to autism spectrum disorder and intellectual disability, hereditary neuropathies, segmental forms of progeria, and Alzheimer’s disease. To understand the biological functions of the ER acetylation machinery, the Puglielli laboratory has -so far- generated ten different mouse models where the intracellular flux of acetyl-CoA is diverted to mimic human diseases. Dr. Puglielli’s aging-oriented research has led to the generation and characterization of mouse models of progeria and Alzheimer’s disease, as well as the identification of novel compounds that delay these phenotypes.

Current Funding: RO1 (PI), RF1 (PI), R35 (Co-I) and P30 (Co-I) from the NIH and Merit Award from the VA

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Picture of T32 Mentor Federico ReyFederico Rey, PhD

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Dr. Federico’s research program focuses on gut microbiome and its impact on metabolism and human health. There is converging evidence that gut microbes and their associated genes (microbiome) affect human physiology and health. Results from several studies have shown that host diet determines gut microbial metabolism that in turn modifies the impact of many dietary components. Thus the gut microbiota can be targeted through diet to promote health. Research in Dr. Rey’s lab focuses on the potential interactions between microbiota and diet that impact health, and could be targeted for therapeutic dietary interventions. Ongoing studies in his lab identify human gut bacterial species that modify some of the dietary components (e.g., choline, flavanoids), the genes involved in these processes, their regulation and the potential impact on the development of cardiovascular disease.

Current Funding: RO1 (PI), USDA grant (PI), Wisconsin Alumni Research Foundation (WARF) grant (PI)

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Picture of T32 Mentor Carol RyffCarol Ryff, PhD

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Dr. Ryff is Director of the UW Institute on Aging (IOA), and leads an NIH-funded internationally renowned study, entitled “Mid-Life in the United States (MIDUS). Her research interests relate to the study of positive aging as an integrated biopsychosocial process, with a special focus on well-being and resilience to aging-associated diseases. The major objective of MIDUS and related studies is on the study of psychosocial, sociodemographic, neurobiological and physical function outcomes in healthy aging and resilience to age-related diseases. One area of special interest in MIDUS is on positive attitude and its potential relationship to psychosocial and physical well-being.

Current Funding: NIA PO1 (PI), NIA R37 (PI), RO1 (PI), NIA U19 (PI)

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Picture of T32 Mentor Miriam ShelefMiriam Shelef, MD, PhD

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Dr. Shelef’s research aims to solve the mysteries of how and why systemic autoimmunity develops and persists in order to guide the discovery of better clinical tests and improved treatments. To this end, there are currently two major research directions in her lab. First, her research group aims to define the role of citrullination and the citrullinating peptidylarginine deiminase enzymes in immunity, inflammation, and rheumatoid arthritis. Second, her team uses traditional methodology and cutting-edge high density array technology with innovative statistical methods to discover new autoantibody targets as well as novel features of antibody and autoantibody reactivity in rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune and inflammatory diseases.

Current Funding: CDMRP (PI)

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Picture of T32 Mentor Vikas SinghVikas Singh, PhD

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Dr. Singh is a computer scientist who works on image analysis, computer vision and machine learning problems. In aging/dementia research, some of his recent work focuses on designing novel algorithms for analysis of structural brain connectivity, modeling longitudinal image datasets and brain changes over time using deep learning methods as well as statistical methods and tests to  pool and harmonize data (both imaging and non-imaging) across multiple sites. Dr. Singh is a scientist in the Wisconsin ADRC and has helped integrate multidimensional data to answer clinically relevant questions in the field of dementia research.

Current Funding: 3 RO1s (PI), 2 NSF grants (PI), R21 (MPI), 3 NIH grants Co-I (RO1, U54, UL1)

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Picture of T32 Mentor Darryl ThelenDarryl Thelen, PhD

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Dr. Thelen is the Weideman Professor of Mechanical Engineering and Biomedical Engineering at UW-Madison. His neuromuscular biomechanics lab develops computational models, novel sensor technologies and dynamic imaging protocols to investigate the structure, mechanics and behavior of musculoskeletal tissues within the human body. Current projects are aimed at enhancing the precision of total knee joint replacement, investigating aging effects on tendon tissue mechanics, identifying biomechanical factors that contribute to osteoarthritis and improving orthopedic treatments of gait disorders in children. His research has been supported by the NIH, NSF and a number of private companies and foundations. Dr. Thelen received his bachelor’s degree in mechanical engineering from Michigan State University in 1987 and his MSE and PhD degrees in mechanical engineering from the University of Michigan in 1988 and 1992, respectively. He has been on the faculty of the University of Wisconsin-Madison since 2002.

Current Funding: RO1 (MPI), R01 (PI), R21 (PI), WARF grant (PI)

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Picture of T32 Mentor David WassarmanDavid A. Wassarman, PhD

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Dr. Wassarman’s research focuses on the genetics of traumatic brain injury (TBI). He uses genetically diverse fruit fly lines to address the hypothesis that TBI accelerates the normal aging process. Using a spring-loaded device to inflict TBI in flies, he has found several connections between TBI and aging, (i) TBI leads to worse outcomes in older flies than younger flies, (ii) TBI reduces the lifespan of flies, (iii) TBI activates molecular pathways that are progressively activated during normal aging, and (iv) mutations and other interventions that improve the outcomes of TBI also increase the lifespan of uninjured flies. Furthermore, in direct support of the hypothesis that TBI accelerates aging, the response of injured flies to another injury is similar to that of older flies to an initial injury. Dr. Wassarman is currently using the fly TBI model to elucidate the molecular and cellular pathways by which mechanical head injury increases the risk of Alzheimer’s Disease (AD) and AD-related dementia.

Current Funding: RF1 (PI)

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