Joseph A. Baur

Associate Professor

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215-746-4585
baur@pennmedicine.upenn.edu

Smilow Center for Translational Research

3400 Civic Center Blvd, Room 12-114

Philadelphia, PA 19104

Research Description

The Baur lab is interested in the basic mechanisms that lead to aging. Age is the most important risk factor for many of the diseases affecting Western society today, including cancer, cardiovascular disease, and neurodegenerative disorders. Although the causes of aging are not known, it can be delayed experimentally in rodents by decreasing energy intake in the absence of malnutrition (caloric restriction, CR) and by a growing number of drugs, such as rapamycin. Elucidating the mechanism(s) by which lifespan can be extended is expected to yield insights into the causes of aging and to highlight new therapeutic approaches to the prevention and treatment of age-related disease.

A major focus of the lab is on nicotinamide adenine dinucleotide (NAD) metabolism. NAD is a critical redox cofactor in mammalian metabolism and serves as a co-substrate for several classes of signaling enzymes including sirtuins, which mediate some effects of CR. Over the past decade it has been shown that supplemental NAD precursors can improve metabolism and alleviate age-related diseases in rodents. We use a combination of transgenic approaches and heavy isotope labeling to understand how and where changes in NAD availability influence health. These include tissue-specific gain and loss of function experiments with nicotinamide phosphoribosyltransferase (Nampt), a key enzyme in the “salvage” pathway for NAD synthesis and isotope-based tracing of nicotinamide riboside and mononucleotide metabolism. Recently, we described SLC25A51 (MCART1) as a transporter responsible for the import of NAD into mammalian mitochondria, where it plays essential roles in the tricarboxylic acid cycle and delivery of electrons to complex I of the electron transport chain.

We also have a series of projects focused on the mechanisms by which rapamycin affects metabolism in mice. Rapamycin was the first compound to be unambiguously shown to extend the maximum lifespan of a mammalian species and remains one of the most robust interventions to promote longevity in mice. However, the underlying mechanisms are debated, and side effects including immune modulation, increased risk of diabetes, and elevation of cardiovascular risk factors are likely to limit the utility of the drug in humans. We have shown that in addition to inhibiting its canonical target, mTOR complex 1, chronic rapamycin treatment disrupts mTOR complex 2 in vivo, resulting in insulin resistance. In contrast, the hyperlipidemic effect of rapamycin appears to be mediated at least in part by the loss of mTOR complex 1 signaling in adipocytes. Ultimately, we hope to use a deeper mechanistic understanding to separate the effects of rapamycin on longevity from its undesirable side effects.

Our broad goal is to identify molecular mechanisms underlying CR and other longevity-promoting interventions that are amenable to nutritional or pharmacological manipulation and can be translated into therapies to prevent or treat age-related diseases in humans.

Diversity & Inclusion Initiatives

  • Faculty mentor for Penn-PREP, Penn-PORT, STEP-UP, USSP, and multiple student exchange programs
  • Diversity Search Advisor for the Department of Physiology 2018-present
Degrees & Education

BScH (Chemistry) Acadia University, Wolfville, Nova Scotia, Canada, 1998

PhD (Integrative Biology) UT Southwestern Medical Center, Dallas, Texas, 2003

Honors & Awards

2008-2012 K99/R00 Pathway to Independence Award

2010-2014 New Scholar Award, Ellison Medical Foundation

2013 Joseph A. Pignolo, Sr. Award in Aging Research

2018-2020 Keith Michael Andrus Cardiac Research Award, Friedreich’s Ataxia Research Alliance

2020 Collaborative Scientist Grant, American Society of Transplant Surgeons

Other Perelman School of Medicine Affiliations

Institute for Diabetes, Obesity, and Metaboli

Institute on Aging

Cell Biology, Physiology, and Metabolism Graduate Group

Biochemistry and Molecular Biophysics Graduate Group

Professional Affiliations

Gerontological Society of America

American Aging Association

Recent Publications
March 14, 2022
Dietary Vitamin E intake is associated with a reduced risk of developing digestive diseases and NAFLD
Joseph A. Baur, Ph.D.
Scorletti E, Creasy KT, Vujkovic M, Vell M, Zandvakili I, Rader DJ, Schneider KM, Schneider CV.
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May 5, 2021
Loss of FOXO transcription factors in the liver mitigates stress-induced hyperglycemia
Joseph A. Baur, Ph.D., Paul Titchenell, Ph.D.
Garcia Whitlock AE, Sostre-Colón J, Gavin M, Martin ND, Baur JA, Sims CA, Titchenell PM - doi:10.1016/j.molmet.2021
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September 23, 2021
NAD+ flux is maintained in aged mice despite lower tissue concentrations
Joseph A. Baur, Ph.D.
McReynolds MR, Chellappa K, Chiles E, Jankowski C, Shen Y, Chen L, Descamps HC, Mukherjee S, Bhat YR, Lingala SR, Chu Q, Botolin P, Hayat F, Doke T, Susztak K, Thaiss CA, Lu W, Migaud ME, Su X, Rabinowitz JD, Baur JA - doi: 10.1016/j.cels.2021.09.001
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December 23, 2021
Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function
Joseph A. Baur, Ph.D.
Dierickx P, Zhu K, Carpenter BJ, Jiang C, Vermunt MW, Xiao Y, Luongo TS, Yamamoto T, Martí-Pàmies Í, Mia S, Latimer M, Diwan A, Zhao J, Hauck AK, Krusen B, Nguyen HCB, Blobel GA, Kelly DP, Pei L, Baur JA, Young ME, Lazar MA - doi: 10.1038/s44161-021-00001-9
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January 18, 2021
Longevity pathways in stress resistance: targeting NAD and sirtuins to treat the pathophysiology of hemorrhagic shock
Joseph A. Baur, Ph.D.
Sims CA, Labiner HE, Shah SS, Baur JA - DOI: 10.1007/s11357-020-00311-z
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November 10, 2020
Increased mTOR activity and metabolic efficiency in mouse and human cells containing the African-centric tumor-predisposing p53 variant Pro47Ser
Joseph A. Baur, Ph.D.
Gnanapradeepan K, Leu JI, Basu S, Barnoud T, Good M, Lee JV, Quinn WJ, Kung CP, Ahima R, Baur JA, Wellen KE, Liu Q, Schug ZT, George DL, Murphy ME - DOI: 10.7554/eLife.55994. PMCID: PMC7661039
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December 15, 2020
Lactate Limits T Cell Proliferation via the NAD(H) Redox State
Joseph A. Baur, Ph.D.
Quinn WJ 3rd, Jiao J, TeSlaa T, Stadanlick J, Wang Z, Wang L, Akimova T, Angelin A, Schäfer PM, Cully MD, Perry C, Kopinski PK, Guo L, Blair IA, Ghanem LR, Leibowitz MS, Hancock WW, Moon EK, Levine MH, Eruslanov EB, Wallace DC, Baur JA, Beier UH - DOI: 10.1016/j.celrep.2020.108500. PMC7830708
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