The role of the immune system in the protection against infections has been recognized for over a hundred years. However, only recently it has become apparent that inflammatory components of the immune system are often elevated in aged individuals and associated with high incidence of non-communicable diseases such as cancer, cardiovascular disease and neurodegenerative disorders, among others.
The Furman lab integrates systems-level immunity in humans to accelerate knowledge of how the immune system affects aging and related chronic disease. Central for this research is the use of state-of-the art technological platforms to measure multiple levels of the immune system in large human cohorts and the application of advanced analytics by artificial intelligence and machine learning to cope with these large volumes of data (‘Big Data’). We collaborate closely with multiple Buck faculty to help defining the immune pathways and circuitries affected by aging and linked to chronic disease states.
Why it matters
Non-communicable diseases of aging are the #1 killer worldwide with a yearly estimated burden of $2.3 trillion only in the US (90% of the total annual health expenditures). It is now a consensus that Systemic Chronic Inflammation (SCI), arising as an immune response to environmental and social insults (known as the ‘exposome’), is the root cause of these diseases, which include cardiovascular disease, cancer, neurodegenerative disorders, musculoskeletal conditions, and many others. Identifying metrics and understanding the role of SCI on the pathophysiology of these age-related diseases is now transforming healthcare as it enables people take control of their health and accelerates discovery of therapeutics, which will result in a significant reduction of disease burden.
Applied Artificial Intelligence is helping us to unravel the complex interactions between environment, immunity & aging and it is transforming preventative medicine and therapeutics.
David Furman, PhD
Dr. David Furman obtained his Doctoral degree in immunology (summa cum laude) from the School of Medicine, University of Buenos Aires, Argentina, for his work on cancer immune-surveillance. During his Postdoc at the laboratory of Professor Mark M Davis, (Stanford) he conducted cutting-edge research in Data Science and Systems Immunology to answer scientific questions with strong potential for translational medicine, including the effect of immunity in aging and age-related disease.
Dr. Furman moved to University of Bordeaux, France, where he studied the involvement of the endocrine and immune systems in human aging and in kidney transplantation, and then helped to create the Systems Biology Department at the Sidra Medical Research Center in Doha, Qatar. Before joining as an Principal Investigator at the National Scientific and Research Council, Buenos Aires, Argentina, Dr. Furman was back to Stanford to take the role of Senior Scientist at the Institute for Immunity, Transplantation and Infection (ITI), and his work involved the use of high-bandwidth/high-throughput technologies to measure immune function; and Machine Learning tools to better define the role of the immune system in cardiovascular aging.
Juliet Bartleson, PhD Postdoctoral Research Fellow
Juliet received her bachelor’s degree in molecular and cell biology and physiology from Sonoma State University in Rohnert Park, California, in 2015. Her undergraduate research focused on a protein involved in proximal T cell receptor signaling, instilling in her a fascination with how immune cells function. She then joined the Immunology PhD program at Washington University in St. Louis, where she worked in the laboratory of Dr. Paul Allen researching how tonic T cell receptor signaling influences CD4+ T cell function. After receiving her PhD in 2020, she joined the laboratories of Drs. David Furman and Daniel Winer at the Buck Institute to integrate her passion for immunology and desire to focus on human-related health in aging.
Zoe "Huixun" Du PhD Candidate, USC-Buck Biology of Aging Program
Huixun "Zoe" Du joined the Furman lab as a graduate student from the University of Southern California-Buck Biology of Aging Ph.D. program in January 2020. Prior to this, she completed her B.S. in pharmaceutical sciences at the University of California-Irvine. She is thrilled to study the dynamics of inflammasomes in aging-associated systemic chronic inflammation using computational tools.
Anissa Grawe Research Associate / Lab Manager
Anissa is a passionate researcher and laboratory manager in the Furman Lab with extensive experience in molecular biology, cell culture, microscopy, and biochemistry. Prior to completing her Master’s degree in cell and molecular biology, Anissa obtained research and managerial experience in various academic settings in the SF Bay Area, including serving as lab manager in the UCSF Cardiovascular Institute in the lab of Dr. Harold Bernstein. She also has prior experience in the private sector at a startup developing portable diagnostic devices for HIV and other communicable diseases. Her expertise ranges from using fission yeast to investigate important proteins in cell division to studying organogenesis, myogenesis, and neuroblastoma in mice. She is excited to be a part of a lab that uses artificial intelligence and machine learning to examine how the exposome is involved in chronic inflammation pathways and their role in aging.
Henry Huang, PhD Data Scientist and Postdoctoral Research Fellow
Henry received his BA in molecular cellular biology from the University of California, Berkeley, and his PhD in biomedical informatics from the University of California, San Diego. He has worked to decipher the role Th17 cells play in the progression of multiple sclerosis at Stanford University before moving on to pursue a PhD in computational biology. During his PhD, he focused on building machine learning models by integrating medical data from different medical systems in a privacy preserving manner that does not disclose sensitive patient level information. By using contextual word embedding, a natural language processing technique, he developed models that incorporate information from different local sources, allowing for more accurate models that is capable of producing less biased and insignificant results than models built from isolated local source. He is currently working to apply the same principles in the field of bioinformatics, attempting to harmonize data from different -omics sources to paint a better picture of the aging process and the related immune responses.
Nikola Markov, PhD Postdoctoral Fellow Bioinformatics
Nikola Markov is a postdoctoral fellow who joined the Furman lab in Sept 2020. He received his Ph.D in Neuroscience for his studies of the structural organization of the Macaque cortical network. He holds a B.S in Cell Biology and Physiology from the University Claude Bernard in Lyon France. He moved to the US in 2011 to join the labs of Michael Higley and Xiao Jing Wang where he applied optogenetic methods to study the synaptic properties of a novel fronto-occipital projections playing role in establishing visual attention. He later joined the lab of Timothy Bushman where he built new experimental systems for primate and rodent behavior control and developed high density multi-electrode devices to record neural activity in animals performing a gating of working memory task. After a short stint at Stanford university he has joined the Buck institute to expand his understanding of the role of chronic inflammation in the processes of aging especially as it relates to the neural system.
Khiem Nguyen Data Scientist
Kevin Perez Bioinformatics Research Fellow
Kevin received his MS in Computer Science from New York Univesity, and his MS in Biomedical Sciences from Paris V Descartes University. He has held software engineer positions in tech companies (IBM) and startups. Before joining the Buck, Kevin was a computational biologist at Hopital Saint-Louis in Paris, and at the Broad Institute of MIT and Harvard, working on Inflammatory Bowel Disease. His current research focus is on aging and senescent cells.
Dina Radenkovic, MD Senior Visiting Scientist
Dina is an academic doctor and medical technology entrepreneur, specialized in the computational biology of aging. She is also a Partner at the Programmable Biology SALT Fund. She qualified with a dual degree in medicine and physiology from UCL Medical School, with the elective at the New England Journal of Medicine, Harvard University, awarded number one in preclinical medicine and the best overall performance in physiology BSc. She founded Be The Change UCL, and won the National NHS Quality Improvement Championship in 2016. Dina also helped set up Hooke, an elite longevity research clinic, in collaboration with the Buck Institute for Aging in London. She has worked at the Barts Heart Centre where she co-developed and brought to market the first imaging algorithm for cardiac MRI based on fractal geometry. She later worked as a Research Fellow at King's College London Department of Twins Research and at Harvard University. Dina did her residency at St Thomas’ Hospital in London. She set up 2 clinical trials of medical devices in the UK. She has over 30 academic papers, 7 grants and over 40 scientific conference presentations. She is fluent in 5 languages and 3 programming languages. She is the SALT Young Global Leader, member of the Founders Forum, Forbes and the World Economic Forum. Dina is visiting the Buck from Hooke London and SALT Bio Fund.
Nazish Sayed, Yingxiang Huang, Khiem Nguyen, Zuzana Krejciova-Rajaniemi, Anissa P. Grawe, Tianxiang Gao, Robert Tibshirani, Trevor Hastie, Ayelet Alpert, Lu Cui, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Rita Ostan, Daniela Monti, Benoit Lehallier, Shai S. Shen-Orr, Holden T. Maecker, Cornelia L. Dekker, Tony Wyss-Coray, Claudio Franceschi, Vladimir Jojic, François Haddad, José G. Montoya, Joseph C. Wu, Mark M. Davis & David Furman. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nature Aging volume 1, pages 598–615 (2021).
Cesar J. Lopez Angel, Edward A. Pham, Huixun Du, Francesco Vallania, Benjamin J. Fram, Kevin Perez, Thai Nguyen, Yael Rosenberg-Hasson, Aijaz Ahmed, Cornelia L. Dekker, Philip M. Grant, Purvesh Khatri, Holden T. Maecker, Jeffrey S. Glenn, Mark M. Davis, and David Furman. Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proc Natl Acad Sci. 2021 Apr 6;118(14):e2022928118.
- Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando T, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Chronic Inflammation in the Etiology of Disease Across the Lifespan. Nature Medicine volume 25, pages 1822–1832 (2019).
- Alpert A, Pickman Y, Leipold M, Rosenberg-Hasson Y, Ji X, Gaujoux R, Rabani H, Starosvetsky E, Kveler K, Schaffert S, Furman D, Caspi O, Rosenschein U, Khatri P, Dekker CL, Maecker HT, Davis MM, Shen-Orr SS. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nature Medicine volume 25, pages 487–495 (2019).
- Sayed N, Gao T, Tibshirani R, Hastie T, Cui L, Kuznetsova T, Rosenberg-Hasson Y, Ostan R, Monti D, Lehallier B, Shen-Orr S, Maecker HT, Dekker CL, Wyss-Coray T, Franceschi C, Jojic V, Haddad F, Montoya JG, Wu JC, Furman D. An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans. bioRxiv, 840363, 2019.
- Davis MM, Tato CM, Furman D. Systems Immunology: Just Getting Started. Nature Immunology 2017 Jun 20;18 (7):725-732.
- Alpert A, Pickman Y, Leipold M, Rosenberg-Hasson Y, Ji X, Gaujoux R, Rabani H, Starosvetsky E, Kveler K, Schaffert S, Furman D, Caspi O, Rosenschein U, Khatri P, Dekker CL, Maecker HT, Davis MM, Shen-Orr SS. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat Med. 2019 Mar;25(3):487-495.
- Blazkova J, Gupta S, Lui Y, Gaudilliere B, Ganio EA, Bolen CR, Saar Dover R, Fragiadakis GK, Angst MS, Hasni S, Aghaeepour N, Stevenson D, Baldwin N, Anguiano E, Chaussabel D, Altman MC, Kaplan M, Davis MM, Furman D. Multicenter systems analysis of human blood reveals immature neutrophils in males and during pregnancy. Journal of Immunology 2017;198(6):2479-2488.
- Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Dechanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nature Medicine 2017;23(2):174-184.
- Shen-Orr S*, Furman D*, Kidd B, Haddad F, Lovelace P, Huang Y-W, Rosenberg-Hasson Y, Mackey S, Grisar FA, Pickman Y, Maecker H, Chien YH, Dekker C, Wu JC, Butte AJ, Davis MM. Defective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humans. Cell Systems 2016;3(4):374-384.
- Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell 2015;160(1-2):37-47.
- Furman D, Jojic V, Sharma S, Shen-Orr S, Lopez Angel CJ, Onengut-Gumuscu S, Kidd B, Maecker HT, Concannon P, Dekker C, Thomas PG, Davis MM. Cytomegalovirus infection enhances the immune response to influenza. Science Translational Medicine 2015;7(281):281ra43.
- Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, Laserson J, Marshall EL, Seo K, Lee JY, Furman D, Koller D, Dekker CL, Davis MM, Fire AZ, Boyd SD. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. Journal of Immunology 2014;192(2):603-11.
- Furman D*, Jojic V*, Kidd B, Shen-Orr S, Tse T, Lund P, Maecker H, Dekker C, Koller D, Davis MM. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Molecular Systems Biology 2013, 9:659.
Dr. Furman’s Pubmed link