A mission-driven community of investigators
The Buck is a collective of the world’s top scientists in the field of research on aging who are sharing their methods and expertise to find ways to help everyone lead fuller, healthier lives by ending age-related disease.
A rather disruptive bunch
The Buck Institute’s 20 principal investigators share the audacious notion that biological aging is malleable. Some of our scientists have been here since the Institute opened its doors; others are newcomers. They all bring their specific areas of expertise to collaborations intended to push the boundaries of scientific inquiry.
Akos Gerenscer, PhD
Assistant Director of the Morphology and Imaging Core and Research Associate Professor
Dr. Akos Gerencser has a dual background in medicine and biomedical engineering. He is experienced in mitochondria-and cell physiology-related, fluorescence microscopy-based technique development. He has designed the oxygen consumption rate calibration algorithm of the Seahorse Extracellular Flux Analyzer. He has developed a set of image processing technologies specifically designed for quantification of mitochondrial calcium, shape changes and motion in fluorescence microscopy recordings. He has studied the role of mitochondrial dynamics in neuronal apoptosis and neurodegeneration, as well as bioenergetics and mitochondrial dysfunction in neurodegenerative disease models and mechanisms of insulin secretion in pancreatic beta cell models. His current interest is the development of mitochondrial membrane potential assays that report potentials in absolute millivolts independently of the plasma membrane potential and geometric factors.
As Assistant Director of the Morphology and Imaging Core, Akos Gerencser, PhD, is available to discuss high-level imaging collaborative ideas, particularly live cell imaging, deep tissue imaging, and multispectral imaging.
Christopher Wiley, PhD
Research Assistant Professor
Dr. Wiley’s research focuses on the study of aging in the context of cellular metabolism, particularly as it pertains to the process known as cellular senescence. Cellular senescence is a stress response by which cells adopt a state of permanent mitotic arrest. More than simple arrest, the senescent phenotype is complex and includes a senescence-associated secretory phenotype (SASP) that leads to secretion of multiple biologically active molecules, including proinflammatory cytokines, matrix metalloproteinases, and growth factors, that can have potent effects on the tissue microenvironment. Recently, a series of advancements have placed both senescence and the SASP at center stage with regard to variegated maladies associated with aging. Despite these advancements, senescence is still studied largely in the context of replicative exhaustion, genotoxic stress, or oncogene activation, all of which result in highly similar senescent phenotypes.
Christopher’s work has focused on two areas. First, he identified compromised mitochondrial function as a potentially important inducer of senescence. Unlike other inducers of senescence, mitochondrial dysfunction drives senescence with a distinct SASP. This new paradigm for senescence highlights the plasticity of the senescent phenotype and reveals an unexplored vector by which mitochondrial dysfunction can drive aging phenotypes such as lipodystrophy, thinning skin, and cancer. Second, he found that senescent cells secrete several eicosanoids, which are signaling lipids that promote inflammation, fever, hair loss, parturition, asthma, fibrosis, and other conditions. This senescence-associated eicosanoid biosynthesis acts to promote the SASP, reinforce mitotic arrest, and promote pulmonary fibrosis. Together, his findings reveal new insights regarding the nature of cellular senescence and offer alternative avenues for intervention for associated disorders such as aging.
Brian Ackrell, PhD
Michelle Arkin, PhD
Professor, Pharmaceutical Chemistry, University of California, San Francisco
Co-Director, Small Molecule Discovery Center, UCSF
Member, Helen Diller Family Comprehensive Cancer Center, UCSF
Adjunct Professor, Buck Institute for Research on Aging
Michelle’s research focuses on developing first-in-class chemical probes and drug leads for novel therapeutic targets in age-related diseases such as cancer and neurodegeneration. Her lab is particularly interested in using small-molecule and protein tools to dissect protein-protein interaction networks relevant to disease. Michelle also co-directs the UCSF Small Molecule Discovery Center (SMDC), which includes high-throughput screening, fragment-based lead discovery, and medicinal chemistry. In a typical year, the SMDC works with more than a dozen academic and pharmaceutical labs to develop novel screening assays and discover starting points for chemical biology and drug discovery.
Michelle is deeply involved in the Academic Drug Discovery community. She is the President of the Academic Drug Discovery Consortium and represents UCSF in the National Cancer Institute’s Chemical Biology Consortium and the Accelerating Therapeutics for Opportunities in Medicine (ATOM) consortium; she is also an investigator in the Rainwater Foundation’s Tau Consortium. Michelle is on the editorial boards for the Assay Guidance Manual and Current Protocols in Chemical Biology. Prior to UCSF, Michelle was a founding scientist at Sunesis Pharmaceuticals, where she helped discover and develop the anti-inflammatory drug lifitigrast (developed by SARcode/Shire), and anti-cancer experimental therapeutic vosaroxin (Sunesis).
Rochelle (Shelley) Buffenstein, PhD
Senior Principal Investigator
Rochelle (Shelley) Buffenstein is currently a Principal Investigator at Calico Life Sciences. Prior to joining Calico in 2015 she was a professor at City University of New York and University of Texas Health, San Antonio. Shelley is also a past President of the American Aging Association (2013-2014) and past-Chair of both the Gerontological Society of America’s Biological Sciences (2015) and the Keystone Symposia on Pushing the Limits to Longevity (2018). She has more than 200 publications, which, in recent years, have focused on molecular and physiological mechanisms that may prolong good health and extreme longevity in rodents.
Shelley is a comparative biologist with more than 25 years of experience studying molecular and physiological mechanisms associated with evolutionary fitness and lifespan. Although she has worked on more than 100 species, a key focus has been the biology of the exceptionally long-lived naked mole-rat. Using numerous kinds of assessments, she has found that naked mole-rats show markedly delayed and attenuated age-related declines in all organ systems. Moreover, unlike other mammals, these rodents show no increase in mortal hazard risk as they get older. She pioneered the use of the naked mole-rat as a pertinent animal model for delayed and attenuated aging and evaluates shared and private mechanisms that may contribute to their aging phenotype with those employed by humans, another long-living species on the basis of body size.
J. Cesar Cardenas, PhD
Associate Professor, Center for Integrative Biology, Universidad Mayor, Chile
Adjunct Professor, Buck Institute for Research on Aging
Adjunct Professor, Department of Chemistry and Biochemistry, University of California, Santa Barbara
J. Cesar Cardenas earned his Ph.D. at the University of Chile, where he studied the mechanism that regulated nuclear Ca2+ homeostasis under Dr. Enrique Jaimovich’s mentoring. Then he moved to the University of Pennsylvania where he performed a postdoctoral training in Dr. Clara Franzini-Armstrong lab, focus in determine the nuclear localization of 1,4,5-trisphosphate receptor (InsP3R) Ca2+channel by using high resolution electron microscopy and cryofracture. Motivate in gain a better understanding of the physiological role of the InsP3R he joined Dr. Kevin Foskett’s lab also at the University of Pennsylvania, where he developed a strong interest in the regulation of cellular metabolism and bioenergetics by Ca2+. In 2012 he joined the Anatomy and Cell Developmental Biology Program at the Institute of Biomedical Science of the University of Chile to study the regulation and role of mitochondria in cancer. In 2016 he became one of the principal investigators of the Geroscience Center for Brain Health and Metabolism (GERO), a Chilean aging center and in 2018 move to Universidad Mayor as an Associated Professor of the Center for Integrative Biology. In addition, he holds and adjunct position at the University of California Santa Barbara. In his lab, Cardenas is exploring the role of the mitochondria-endoplasmic reticulum communication in the generation and maintenance of firstname.lastname@example.org
Felipe Court, PhD
Professor, Center for Integrative Biology, Universidad Mayor de Chile
Adjunct Professor, Buck Institute
Felipe A. Court received his PhD at Edinburgh University under the supervision of Dr. Peter Brophy and Dr. Richard Ribchester, working on fundamental parameters that regulates conduction velocity in the nervous system. During this time, Court was awarded with the UK best PhD by the British Neuroscience Association. Under an EMBO postdoctoral fellowship he then worked in demyelinating conditions and in vitro models for neuron-glia interaction in the laboratories of Dr. Laura Feltri and Dr. Larry Wrabetz at the San Raffaele Scientific Institute, Milano. In 2008, Court joined the Department of Physiology at Catholic University in Chile to study transfer of genetic material between glial cells and neurons. In 2016, Court moved to Universidad Mayor (Chile) as a Full Professor and become Director of the Center for Integrative Biology, and principal investigator of the Center for Geroscience, Brain health and Metabolism (GERO). In his lab, Court is working with mouse models of neurodegenerative conditions, including Alzheimer’s and Parkinson, as well as glia-derived inflammatory events in the CNS during ageing, studying the molecular mechanisms associated to axonal degeneration. In addition, his group is studying transfer of genetic material (mRNA and miRNA) from glia to neurons via exosomes, and the impact of this process in axonal regeneration and email@example.com
Christian Gonzalez-Billault PhD
Professor, Faculty of Sciences and Faculty of Medicine, Universidad de Chile
Director, Geroscience Center for Brain Health and Metabolism (GERO)
Adjunct Professor, Buck Institute for Research on Aging
Christian Gonzalez-Billault was initially trained in Biochemistry at Universidad de Chile. He then received his PhD in Cell and Molecular Biology at the Molecular Biology Center Severo Ochoa in Madrid, Spain under the supervision of Jesus Avila. After that he received an award from the Madrid Province to perform a postdoctoral fellow in Madrid. In 2003, he joined the Department of Biology, Faculty of Science, Universidad de Chile where he is currently Full Professor. He recently received a partial appointment at the Department of Neuroscience, Faculty of Medicine, Universidad de Chile. He is also the Director of the Geroscience Center for Brain Health and Metabolism (GERO), an aging center funded under the Priority Areas Program of the Chilean Commission for Science and Technology Research. He was also the President of the Chilean Society for Biology, the oldest and more traditional scientific society in the country. He directed the Cell Molecular and Neuroscience PhD Program at Universidad de Chile. He was part of the Frontiers in Science group at the Chilean Academy of Sciences.
In his lab, Gonzalez-Billault is interested to understand the role of cytoskeleton proteins in neuronal functions, including physiological and pathological aspects. He initiated a successful series of biennial workshop entitled “Emerging Concepts of the Neuronal Cytoskeleton” that was held in 2011, 2013, 2015, 2017 with an additional workshop programmed for 2019. The series had been funded by EMBO, IUBMB, ISN amongst others.
Currently, Gonzalez-Billault research is focused in understanding the effects of aging on brain cells, including neurons and glial cells. We are using neurons produced from skin cells to model aging in vitro; and we are interested to understand the functional and metabolic coupling of astrocytes and neurons during normal aging and in nervous system pathologies. We are also assessing the consequences of senescence in neuronal morpho-structure and functions.
Claudio Hetz, PhD
Professor, Institute of Biomedical Sciences University of Chile
Adjunct Professor, Buck Institute
Visiting Professor, Harvard School of Public Health
Claudio Hetz was originally trained as Biotechnology Engineer at the University of Chile and performed his Ph.D. thesis in Biomedical Sciences at Serono Pharmaceutical Research Institute, Switzerland. This work was performed in the laboratory of Dr. Claudio Soto, and contributed to define the role of ER stress in Prion-related disorders. Then he did a postdoctoral training at Harvard University to study stress responses at the level of proteostasis control and its relation to disease. This work was supervised by Drs Stanley Korsmeyer and Laurie Glimcher, worl lider in apoptosis and ER stress research. He joined the University of Chile during 2007 and is currently Full Professor at Faculty of Medicine, in addition to hold and adjunct Professor position at the Buck Institute for Research in Aging in California and a visiting professor position at Harvard. He is also currently the Co-Director of the Biomedical Neuroscience Institute (BNI) and associate investigator of the Center for Geroscience, Brain health and Metabolism (GERO). His research focused on understanding the molecular basis of protein folding stress, its relationship to pathological conditions affecting the nervous system including ALS, Parkinson´s disease, and Alzheimer’s disease and the development of prototypic strategies to prevent neuronal damage. One of his major areas of biotechnological development is gene therapy. This group is one of the most productive laboratories in Chile and Latin America and is currently supported by various national and international organizations. He has received important award including the KIA International Award, FEBS Anniversary Prize, TWAS-ROLAC and UNESCO Young Scientist Prize as outstanding young scientist in Latin America, the Santander Award, he was finalist in the Eppendorf and Science Award in Neurobiology, and was awarded with the Cell Biology Society and Bios-Chile prize as the best young scientist of Chile. Dr. Hetz H-factor is 50, publishing more than 170 papers with more than 13.000 firstname.lastname@example.org
Nevan J. Krogan, PhD
Professor, Department of Cellular and Molecular Pharmacology
Senior Investigator, Gladstone Institute for Data Science and Biotechnology
Director, Quantitative Biosciences Institute at UCSF
Director, QB3@UCSF, California Institute for Quantitative Biosciences
Director, Thermo Fisher Scientific Proteomics Facility for Disease Target Discovery
Faculty, Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, UCSF
Adjunct Faculty, Sanford Burnham Prebys Medical Discovery Institute
Adjunct Faculty, Buck Institute for Research on Aging
Nevan Krogan is an expert in the field of systems biology and is known for extracting biological mechanism and insight from large-scale biological datasets. Research in the Krogan lab focuses on fundamental biological mechanisms, because cures to many diseases have been revealed by unexpected discoveries in the basic sciences. One of the new approaches developed is reflected in a variety of ‘Cell Mapping Initiatives’, which we apply to many biological or biomedical problems, including infectious diseases (HPMI), cancer (CCMI) as well as neurological and psychiatric disorders (PCMI). In these projects, we create cell maps by comprehensively identifying the protein complexes that work together to ensure healthy cell physiology. Using this information, we study how disease mutations or infections adversely change these protein networks and, ultimately, how drugs or other treatments can overcome these changes. We strongly believe that the best science will be done by diverse groups of scientists coming from different disciplines, which is why we are working in close collaboration with experts from different disciplines on all of our projects. Complementing technologies that allow the unbiased study of protein abundance, protein modifications, and the effects of gene deletions help us inform targeted structural studies, further paving the way to drug development.
During his PhD studies at the University of Toronto under Jack Greenblatt, Nevan developed several experimental systems biology approaches and integrated together the resulting data to interrogate many pathways in budding yeast. During his time as an independent Sandler Fellow at UCSF and then UCSF faculty starting in 2007, he has since extended these approaches to study different disease states in human cells as described above. He is a Searle Scholar, Keck Young Investigator and was recently named one of the top 40 under 40 by the journal Cell. He serves on several journal editorial boards, including Molecular Systems Biology and Cell Systems, and is routinely an organizer of international conferences including meetings in Europe, Asia and the USA. He is also the director and co-director of several NIH-funded Center grants, including the HARC Center (HIV Accessory and Regulatory Complexes), the Cancer Cell Map Initiative (CCMI), the Host Pathogen Map Initiative (HPMI) and the Psychiatric Cell Map Initiative (PCMI).
Deepak A. Lamba, MBBS, PhD
Associate Professor, Department of Ophthalmology UC-San Francisco
Adjunct Professor, Buck Institute
The Lamba lab focuses on retinal repair following inherited and age-associated degeneration and modeling disease-in-a-dish using stem cells technologies. Dr. Lamba’s lab has developed in vitro methodologies for generating all the various retinal cell types, including retinal neurons and retinal pigment epithelium cells, from both human and mouse embryonic stem cells and induced pluripotent stem cells. The research is primarily focused on (1) exploring the potential and challenges in retinal repair and (2) using in vivo models and stem-cell based in vitro model systems to understand various retinal degenerations. Dr. Lamba started his lab at the Buck Institute for Research on Aging in 2011 as an Assistant Professor. His work has been published in top-tier journals including Science, Nature-Metabolism, Cell-Stem Cells and PNAS. In 2018, Lamba lab moved to UCSF’s Department of Ophthalmology and is currently housed at the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research to focus on novel stem cell-based retinal therapies and bringing them closer to the clinic. Dr. Lamba continues to collaborate with faculty at the Buck Institute.Deepak.Lamba@ucsf.edu
David Madden, PhD
Shona A. Mookerjee, PhD
Adjunct Associate Professsor, Buck Institute
Associate Professor, Biological and Pharmaceutical Sciences, Touro University California College of Pharmacy
Shona Mookerjee received her PhD training in Molecular Genetics in the lab of Elaine A. Sia at the University of Rochester, investigating mechanisms of mitochondrial DNA repair (and whether they do or don’t have repair mechanisms — luckily for all of us, they do!) and mitochondrial genome inheritance. She trained as a postdoctoral fellow at the Buck Institute until 2013, and began as an Assistant Professor at Touro University California that year. She teaches in the pharmacy and master’s degree programs at Touro University California College of Pharmacy, and conducts research in the Brand Lab, where she also trains undergraduate and graduate students. Her research program is focused on understanding the energy 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.
Dr. Mookerjee is also a lecturer in the Bioenergetics Master Class led by David Nicholls and Martin Brand.
Marshall Stoller, MD
Alex Zhavoronkov, PhD
CEO, Insilico Medicine
Adjunct Professor, Artificial Intelligence, Buck Institute
Alex Zhavoronkov, PhD, is the founder and CEO of Insilico Medicine, a leader in the next-generation artificial intelligence technologies for drug discovery, biomarker development, and aging research. At Insilico he pioneered the applications of generative adversarial networks and reinforcement learning techniques for generation of novel molecular structures with the desired properties and generation of synthetic biological and patient data. He also pioneered the application of deep learning techniques for prediction of biological age and utilized these predictors for target identification and drug discovery. He set up the R&D centers in 6 countries including the United Kingdom, Korea, Russia, Hong Kong and Taiwan and launched multiple digital biomarker initiatives including Young.AI. Prior to founding Insilico Medicine, he worked in senior roles at ATI Technologies (acquired by AMD in 2006), NeuroG Neuroinformatics, Haut.AI and established AgeNet.net competitions. He is the co-founder and chief science officer (CSO) of the Biogerontology Research Foundation (BGRF, bg-rf.org.uk, a registered UK charity focusing on age-related diseases. Since 2012 he published over 130 peer-reviewed research papers and 2 books including “The Ageless Generation: How Biomedical Advances Will Transform the Global Economy” (Palgrave Macmillan, 2013). From 2014 to 2018 he presented at over 200 academic and industry conferences. He serves on the editorial boards of Aging, Aging Research Reviews, Frontiers in Genetics of Aging, and co-chairs the Annual Aging Research for Drug Discovery Forum (6th annual in 2019) and the Artificial Intelligence for Healthcare Forum (3rd annual) at the Basel Life, one of Europe's largest industry events in drug discovery. Dr. Zhavoronkov holds two bachelor degrees from Queen’s University, a master’s in Biotechnology from Johns Hopkins University, and a PhD in Physics and Mathematics from Moscow State University. List of academic publications.
Dale Bredesen, MD
David Greenberg, MD, PhD
David Nicholls PhD, FRSE
Professor Emeritus of Mitochondrial Physiology
David Nicholls joined the Institute in 2000, establishing the mitochondrial physiology laboratory. His research, over more than 50 years, has focused on the mitochondrion, the powerhouse of the cell and the focus of much current aging research, with over 300 publications that have been cited by other scientists more than 33,000 times. He is perhaps best known for his work on brown fat, solving the mechanism by which this tissue produces heat via a novel protein, UCP1. In addition, four editions of the ‘Bioenergetics’ textbook have introduced the mitochondrial field to generations of scientists. He has developed numerous techniques to measure mitochondrial function in cells, and their dysfunction in aging-related diseases such as type 2 diabetes and stroke. In 2008 he relocated to Sweden, still spending 3-4 months a year at the Institute, working at the bench in the laboratory now directed by Martin Brand.
Dr. Nicholls officially retired in 2016, but continues to be active as Professor Emeritus, collaborating with groups studying diabetes. He sees his main current role as an educator, running mitochondrial ‘master classes’, often together with Martin Brand, and using his half-century experience in mitochondrial bioenergetics to argue in reviews for greater ‘quality control’ in the more than 15,000 annual publications dealing with aspects of mitochondrial physiology in health, aging and disease.
He was elected a Fellow of the Royal Society of Edinburgh in 1999, and was awarded the Mitchell Memorial Medal by the European Bioenergetics Congress in 2008.