The Brand lab is focused on the role of mitochondria in health, disease, and aging. Mitochondria are subcellular structures in which nutrients are oxidized to extract their energy content in the process of oxidative phosphorylation. This energy is then distributed to the rest of the cell to drive the essential machinery of life. However, in addition to releasing energy, nutrient oxidation also produces free radicals and other reactive oxygen species. Impaired energy distribution and excessive free-radical production are thought to be among the primary drivers of aging and age-related disease.
The Brand lab has pioneered new approaches to better understand mitochondrial function and dysfunction within cells and has applied these approaches to investigate the role of mitochondrial energy metabolism in aging and disease. To investigate free-radical production, we have characterized the specific sites and regulation of mitochondrial superoxide and hydrogen peroxide generation and are studying how these sites contribute to cellular oxidative stress and damage. Using high-throughput screening, we have identified novel suppressors of radical formation that do not inhibit energy metabolism, and we are using these exciting new molecules to probe and modulate mitochondrial radical production in cell and animal models of aging and disease.
Why it matters
We envision treatments that would minimize the production of free radicals by mitochondria without inhibiting energy metabolism. Our lab is collaborating with others both inside and outside the Buck to evaluate and mitigate the role of dysfunctional mitochondria in aging and in diseases of aging, including diabetes, cancer, hearing and vision loss, mobility, osteoporosis, heart and kidney disease, stroke, Parkinson’s, Alzheimer’s, and Huntington’s. Research has already opened up new possibilities for the control of these conditions. We aim to cut through the guesswork and establish how free radicals that impact aging and disease are generated and how they can be decreased.
We aim to suppress excessive mitochondrial formation of free radicals to delay or prevent many age-related diseases.
Martin Brand, PhD
Dr. Brand was trained in the United Kingdom at the University of Manchester Institute of Science and Technology, where he received his Bachelor of Science, and at the University of Bristol, where he received his PhD. His postdoctoral work was completed at Johns Hopkins University in Baltimore, Maryland, with Professor A.L. Lehninger. Dr. Brand was a faculty member of the Biochemistry Department at the University of Cambridge and then a group leader at the Medical Research Council in Cambridge. He moved his laboratory to the Buck Institute in 2008. Dr. Brand has made major contributions to understanding the mechanisms of energy transformation and the mechanisms of energetic inefficiency and free-radical production and their roles in evolution, physiology, and the diseases of aging.
Dr. Brand has published over 340 scientific papers, which have been cited more than 33,000 times by other scientists. His research has been recognized with the Keilin Medal of the Biochemical Society and a senior scholarship from the Ellison Medical Foundation, and with his election as a fellow of the Academy of Medical Sciences. He serves on the editorial boards of several scientific journals and the scientific advisory boards of various biotech companies.
B. B.Bérenère Benoit, PhD Postdoctoral Research Fellow
Originally from France, Dr. Benoit obtained her PhD in 2013. During her graduate work, she concentrated on the impact of dietary oils on the intestinal epithelium and more particularly on colonic goblet cells. She did a two-year postdoc at Bergen University, where she worked on the identification of new properties of the intestinal FGF19 factor on the skeletal muscle mass. She joined the Brand lab in September 2017, where she is now studying the role of reactive oxygen species in hypoxia.
Pratiksha Dighe Research Associate (Lab Manager)
Originally from India, Pratiksha worked in an industrial company focused on developing stem cell–based medicinal products before she came to the United States in 2013 to further pursue her graduate studies in biological sciences with a stem cell concentration at Sacramento State University. After her graduation in 2015, she joined the Buck Institute as a part of the Brand lab and has been an integral part of the lab’s team, focusing on the development and testing of the novel suppressors of radical formation.
A. G.Akos Gerencser, PhD Assistant Research Professor, Assistant Director of the Morphology and Imaging Core
Dr. Gerencser received MD and PhD degrees in neurosciences from Semmelweis University in Hungary and an MS in biomedical engineering from Budapest University of Technology and Economics. His completed his postdoctoral work at the Burnham Institute for Medical Research in La Jolla, Calfornia, and subsequently with Dr. David Nicholls at the Buck Institute. He has been working with the Brand lab since 2008, initially as a staff scientist and then as an assistant research professor since 2012. Dr. Gerencser’s research follows an interdisciplinary approach by merging assay technology development for mitochondrial physiology and bioenergetics and the application of these technologies in the fields of neurodegenerative diseases, stem cell biology, and type 2 diabetes mellitus. He has contributed to the now widely used Seahorse Extracellular Flux assay technology and to the understanding of bioenergetic regulation of insulin secretion in pancreatic β-cells. He founded Image Analyst Software, a small business to create a software platform for pipeline-based image analysis for time-lapse microscopy.
C. A.Chad A. Lerner, PhD Postdoctoral Research Fellow
Mitochondrial biology has been a central feature of Dr. Lerner’s research endeavors in cell lifespan biology and age-related diseases. After receiving his PhD in molecular biology at the Drexel College of Medicine in 2013, Dr. Lerner completed a T32 NIH training fellowship at the University of Rochester aimed at exploring the effect of electronic cigarette oxidants on a critical animal lung antioxidant defense system and in mitochondria. His earlier graduate studies tackled questions that shed light on the conferred benefit of converging pathways between rapamycin and low IFG-1 signaling on lifespan that revealed mitochondrial involvement for this effect. As a more recent member of the Brand lab, Dr. Lerner is currently engaged in efforts to expand unique single-cell membrane potential measurement technology and is researching new methods to use pharmacological and mitochondrial transfer techniques for rescuing bioenergetic deficits, a common feature in neurological, metabolic, and musculoskeletal disorders.
Shona A. Mookerjee, PhD Associate Professor
Dr. Mookerjee received her PhD in molecular genetics from the University of Rochester. She trained as a postdoctoral fellow at the Buck Institute until 2013, when she took a faculty position at Touro University California and an adjunct faculty position at the Buck Institute. She teaches in the Department of Biological and Pharmaceutical Sciences at Touro and conducts research in the Brand lab, where she also trains undergraduate and graduate students. Her work is focused on understanding the energetic budgeting of cells and the ways in which energy production and consumption affect cellular behavior in health, disease, and aging. Current projects include the role of ATP production in cellular differentiation and transformation and the characterization of the pathways that consume ATP during these processes.
H. W.Helen Wong Hoi Shan, PhD Postdoctoral Research Scholar
Dr. Shan received her PhD degree in life science from Hong Kong University of Science and Technology. Currently a postdoctoral research scholar in the Brand lab, she focuses on the investigation of pharmacological activities and molecular mechanisms of suppressors of mitochondrial reactive oxygen species production. She has over nine years of experience in assessing mitochondrial functional ability in both cell and animal systems, with practical experience in conducting in vivo/ex vivo experiments using rat and mice models.
Mark Watson, PhD Postdoctoral Research Scholar
Dr. Watson received his bachelor’s degree in biomedical science and his PhD in infection and immunity from the University of Birmingham in the United Kingdom. His research focuses on the implications of mitochondrial ROS in initiating and exacerbating diseases as well as the involvement of intestinal health in aging. Mark serves as a Buck Ambassador, providing scientific outreach to the community.
Y. Z.Yufeng Zhang, PhD Glenn Foundation Postdoctoral Research Fellow
Dr. Zhang received his PhD in biology at the University of South Dakota in 2015 and was a postdoctoral fellow at Auburn University for two years before joining the Brand lab in 2017. Trained as an evolutionary physiologist, he is fascinated by variations and adaptations in animal bioenergetics. Within this broad interest, he has focused on whether adaptations from one stressor could have beneficial or harmful effects to other endeavors throughout an animal’s lifecycle. Currently, he is working with Dr. Judith Campisi on changes in the secretome of senescent cells by manipulating mitochondrial reactive oxygen species production.
- Mookerjee, S. A., Gerencser, A. A., Nicholls, D. G., Brand, M. D. (2017). Quantifying rates, pathways and flexibility of intracellular ATP production and consumption using extracellular flux measurements. Journal of Biological Chemistry, 292, 7189–7207. DOI: 10.1074/jbc.M116.774471. PubMed PMID: 28270511. PMCID: PMC5409486.
- Brand, M. D. (2016 Nov). Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radical Biology and Medicine, 100, 14–31. DOI: 10.1016/j.freeradbiomed.2016.04.001. PubMed PMID: 27085844.
- Brand, M. D., Goncalves, R. L. S., Orr, A. L., Vargas, L., Gerencser, A. A., Borch Jensen, M., Wang, Y. T., Melov, S., Turk, C. N., Matzen, J. T., Dardov, V. J., Petrassi, H. M., Meeusen, S. L., Perevoshchikova, I. V., Jasper, H., Brookes, P. S., Ainscow, E. K. (2016 Oct 11). Suppressors of superoxide/H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia/reperfusion injury. Cell Metabolism, 24, 582–592. DOI: 10.1016/j.cmet.2016.08.012. PubMed PMID: 27667666.
- Orr, A. L., Vargas, L., Turk, C. N., Baaten, J. E., Matzen, J. T., Dardov, V.J., Attle, S. J., Li, J., Quackenbush, D. C., Goncalves, R. L. S., Perevoshchikova, I. V., Petrassi, H. M., Meeusen, S. L., Ainscow, E. K., Brand, M. D. (2015 Nov 11). Suppressors of superoxide production from mitochondrial complex III. Nature Chemical Biology, 11, 834–836. DOI: 10.1038/nchembio.1910. PubMed PMID: 26368590.
- Goncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., Brand, M. D. (2015 Jan 2). Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. Journal of Biological Chemistry, 290, 209–227. DOI: 10.1074/jbc.M114.619072. PubMed PMID: 25389297.
- Brand, M. D., Nicholls, D. G. (2011 Aug 1). Assessing mitochondrial dysfunction in cells. Biochemical Journal, 435, 297–312. DOI: 10.1042/BJ20110162. PubMed PMID: 21726199.