Our Team

Bio

Laura Niedernhofer, MD, PhD, joined the University of Minnesota in July 2018 to direct the new Institute on the Biology of Aging & Metabolism (iBAM) and Medical Discovery Team on the Biology of Aging. She is a professor in the Department of Biochemistry, Molecular Biology and Biophysics. Dr. Niedernhofer’s expertise is in DNA damage and repair, genome instability disorders, cellular senescence and aging. Her research program is centered on studying fundamental mechanisms of aging and developing therapeutics to target them. Her research program implements a murine model of a human progeroid syndrome caused by a defect in DNA repair. She contributed to the discovery of a new class of drugs called senolytics. Dr. Niedernhofer has served on study section for NCI, NIEHS and NIA. She has been awarded for research in aging, cancer and environmental health science. 

Research Summary

Dr. Niedernhofer's research career has been dedicated to investigating the impact of DNA damage on the structure of DNA, cell function and organism health. The DNA in each of our cells is damaged thousands of times per day by exposure to environmental factors, dietary components, chemotherapeutic agents and even endogenous by-products of normal metabolism. Studying patients with rare diseases caused by inherited defects in DNA repair provides important insight into the consequences of DNA damage. These patients have a dramatically increased risk of cancer and age prematurely. The Niedernhofer Lab has engineered mouse models of these genome instability syndromes as a sensitive tool to test hypotheses about how DNA damage promotes cancer and aging.

Bio

Dr. Paul Robbins is a Professor of Biochemistry, Molecular Biology and Biophysics and the Associate Director of the Institute on the Biology of Aging and Metabolism (iBAM) and the Medical Discovery Team on the Biology of Aging at the University of Minnesota.

He was one of the first to identify enhancer elements that regulate transcription at a distance, the first to show that the retinoblastoma tumor suppressor regulates transcription and the first to develop gene therapies for autoimmune disease including an ongoing clinical trial for osteoarthritis. More recently, he was part of a collaborative team that was the first to identify senotherapeutic compounds, able to reduce the senescent cell burden and extend healthspan and lifespan in mouse models, that are in more than 15 clinical trials for age related diseases and conditions.

Research Summary

The pathways important for driving autoimmune and inflammatory diseases as well as age related degeneration are surprisingly similar. For example, inhibition of the transcription factor NF-?B is therapeutic in mouse models of autoimmunity and inflammation as well as Duchenne muscular dystrophy and aging. Similarly, inhibition of IL-1ß signaling by gene transfer of the IL-1 receptor antagonist protein is therapeutic in multiple models of diseases. The Robbins Lab is developing novel approaches to treat autoimmune (type 1 diabetes, rheumatoid arthritis), inflammatory (inflammatory bowel disease, delayed type hypersensitivity) and age-related degenerative diseases using biologics and small molecules. The therapeutic approaches being developed include: 1) AAV mediated gene transfer of anti-inflammatory or immunosuppressive agents; 2) Peptide and small molecule inhibitors of the transcription factor of NF-?B; 3) Novel osteogenic peptides; 4) Adult stem cells; 5) Microvesicles (exosomes) derived from immunoregulatory or stem cells able to block inflammation or promote regeneration; and 6) Identification of drugs able to reverse cellular senescence for improving healthy aging. Although the majority of the studies are being performed in mouse models of disease, approaches to treat osteoarthritis by intra-articular AAV-mediated gene transfer and Duchenne muscular dystrophy by systemic treatment with a NF-?B inhibitory peptide will soon be entering the clinic.

Research Summary

Age is associated with increased inflammation, visceral adiposity and metabolic disease. Tissue resident immune cells are required for dampening inflammation and maintaining tissue homeostasis. There are changes in resident immune cells that drive the increased inflammation and metabolic impairments that are seen with increased age. We are studying the cellular and molecular changes within tissue resident immune cells that drive metabolic impairments in tissues. In particular, we are focused on lipolysis, a metabolic process that is required for release of energetic substrates from stored triglycerides in adipocytes. Lipolysis is impaired in aged individuals and this impairment may contributes to a worsened ability of elderly to maintain a healthy body-weight, stay warm or exercise. Our work has previously shown that adipose tissue immune cells reside in microenvironment niches and are able to inhibit lipolysis in the aged adipose tissue. There are two broad projects within the lab: Adipose tissue macrophage-specific regulatory effects on lipolysis and inflammation during aging Fat-associated lymphoid cluster (FALC) and lymphocyte regulation of metabolism Our lab focuses on mouse models of aging and uses a wide variety of techniques to investigate the changes occurring with age. We combine this in vivo approach with a complementary in vitro cell culture system to better understand a direct mechanism. Ultimately, our goal is to generate candidates that could be targets for therapeutically treating to improve health span and restore metabolism in the elderly.

Bio

Dr. Dong obtained his PhD in bioinformatics in the Shanghai Institutes of Biological Sciences at the Chinese Academy of Sciences in 2013. He completed postdoc training in the Department of Genetics at the Albert Einstein College of Medicine in 2021. Since 2021, he started the Xiao Dong laboratory in the Institute of the Biology of Aging (iBAM) and the Department of Genetics, Cell Biology and Development (GCD) at the University of Minnesota, Twin Cities.

Research Summary

Aging is a universal trait that is characterized by a progressive loss of physiological integrity, leading to declined function in tissues and increased vulnerability to disease and death. It has been long hypothesized that the functional decline in aging is caused by genome instability. The general interest of the Zhang Lab focuses on the somatic genome and epigenome instability in aging and longevity. More specifically we study somatic DNA mutations and epi-mutations and their effects on cellular functional decline in normal aging process or age-related diseases. We have been developing experimental approaches of single-cell multi-omics and applying them to discover interactions of genome, transcriptome and epigenome in individual cells from different tissues of humans during aging or species with different maximum life spans.

Bio

Dr. Revelo is an Associate Professor in the Department of Integrative Biology & Physiology and Center for Immunology. He has a broad background in physiology, immunology, and metabolism and expertise in inflammation during cardio-metabolic disease. His research explores the role of the immune system and inflammation in the pathophysiology of obesity-related diseases such as fatty liver disease and heart failure.

Research Summary

Dr. Revelo's research program focuses on the following areas:
1. Mechanisms of hepatic and intestinal inflammation in fatty liver disease and cancer.
2. Immune mechanisms of cardiac remodeling during heart failure
3. Anti-inflammatory mechanisms of exercise training and bariatric surgery