Peer-Reviewed Scientific Publications

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy

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.

In this study, the authors demonstrate that neutrophils, a type of immune cells involved in the first line of defense to pathogens, are generally more functionally immature in males compared to females and during pregnancy, which may explain why the innate immune response of males and during pregnancy is suboptimal compared to those of females.

Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

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.

The authors of this study identify new danger associated molecular patterns (DAMPs) found in the blood of a subset of older adults, which broadly activate the immune system, inducing inflammation, hypertension and arterial stiffness, and generally contribute to cardiovascular aging in mouse and humans.

Defective Signaling in the JAK-STAT Pathway Tracks with Chronic Inflammation and Cardiovascular Risk in Aging Humans

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 Systems2016;3(4):374-384.

In this elegant study, a broad cellular pathway defect is observed in some older adults, which contributes to cardiovascular risk and is linked to chronic systemic inflammation.

IgH sequences in common variable immune deficiency reveal altered B cell development and selection**

Roskin KM, Simchoni N, Liu Y, Lee J-Y, Seo K, Hoh RA, Pham T, Park JH, Furman D, Dekker CL, Davis MM, James JA, Nadeau KC, Cunningham-Rundles C, Boyd SD. IgH sequences in common variable immune deficiency reveal altered B cell development and selection. Science Translational Medicine2015;7(302):302ra135.

This study identifies B cell defects in common variable immunodeficiency (CVID) patients that indicate that immunodeficiency may derive from both decreased diversity of the naïve B cell pool and diminished somatic hypermutation in memory repertoires.

Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences

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.

A multi-parametric ‘omics’ study in a twin cohort that demonstrates that variation in immune phentoypes is mostly driven by environmental influences and not genetics.

Cytomegalovirus infection enhances the immune response to influenza

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.

In this report, the authors analyze the effect of chronological age and cytomegalovirus (CMV), a common latent virus found in the majority of people, in immune system function. With particular focus in the serological response to the Flu virus, the study demonstrates both in humans and mouse models that infection with CMV potentiates the responses against influenza.

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination

Furman D, Hejblum B, Simon N, Jojic V, Dekker CL, Thiebaut R, Tibshirani R, Davis MM. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proceedings of the National Academy of Sciences U S A 2014;111(2):869-74.

A broad view of the immune system in males and females shows that the known enhanced response to vaccinations found in females may be due to an immunosuppressive effect of testosterone with modulating effects in the expression of immune cell genes.

Effects of Aging, Cytomegalovirus Infection, and EBV Infection on Human B Cell Repertoires

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.

An extensive analysis of B cell receptor sequencing, showing differential effects of aging, cytomegalovirus, and Epstein-Barr virus infection in the B cell repertoire.

Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

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.

In this seminal study, the authors identify blood biomarkers of the immunological response to the influenza vaccine involving the apoptosis pathway and exhausted memory cells found in the blood of older adults.