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. Recent ‘systems biology’ approaches to immunology and aging reveal increasing complexities, redundancy and pleiotropic effects of these age-related chronic inflammatory pathways, which largely differ from those induced by infections which trigger acute inflammation.
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.
- Furman D, Carrera-Bastos P, Campisi J, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Slavich GM, Mantovani A, Weyand CM, Barzilai N, Dixit VD, Goronzy JJ, Rando T, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Chronic Inflammation in the Etiology of Disease Across the Lifespan (Nature Medicine, under review).
- Furman D, Gao T, Sayed N, Haddad F, Tibshirani R, Hastie T, Cui L, Kuznetsova T, Rosenberg-Hasson Y, Ostan R, Monti D, Lehallier B, Shen-Orr S, Maecker H, Dekker C, Wyss-Coray T, Franceschi C, Jojic V, Wu J, Montoya J. A Noverl Metric for Chronic Inflammation Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans (Nature Medicine, under review)
- 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