Eric Yager, Ph.D.
Ph.D., Biomedical Sciences, University at Albany
Courses Taught at ACPHS
General Biology I Laboratory
It is estimated that by 2030, nearly one of out every five Americans will be 65 years or older. Such a dramatic increase in the size of the aged population poses new challenges to the U.S. healthcare system as aged individuals exhibit increased susceptibility to infection, cancer, and autoimmunity. Accordingly, the long term research goal of my laboratory is to elucidate those intrinsic and extrinsic alterations in the host immune system that render the elderly more susceptible to disease and less responsive to contemporary vaccine strategies. Our findings have yielded important insights into how the naturally occurring contraction of the naïve T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes critical for protection against pulmonary influenza virus infections. Additionally, results from our studies have indicated that the delivery of multivalent influenza DNA vaccines to the skin via particle-mediated epidermal delivered (PMED, or gene gun) represents an effective vaccination strategy for eliciting robust, broadly protective immunity against seasonal and pandemic strains of influenza in both adults and the vulnerable elderly population.
We have begun to explore the impact of aging on the regulation of host innate immunity and inflammation. Innate immune cells are known to express a collection of molecular “sensors” that allow them to detect microorganisms early during infection. Members of the NOD-like receptor (NLR) family of proteins assemble into large complexes known as inflammasomes inside innate cells after sensing a variety of microbial products or molecules associated with host cell damage. Assembly and activation of the NLRP3 inflammasome leads to the processing and secretion of the proinflammatory cytokine interleukin-1 beta, an important mediator of host inflammation. Since aging is associated with diminished innate immunity, chronic inflammation, and an increased susceptibility to viral infection, the objective of our current studies is to test the hypothesis that biological aging adversely impacts the ability of the NLRP3 inflammasome to properly regulate inflammation and host defense. Results from these studies have the potential to facilitate the identification of new drug targets for the effective treatment of chronic inflammation, and/or the development of vaccination strategies to augment immunity and restore health in the rapidly growing elderly population.
Mathew A, Lindsley TA, Sheridan A, Bhoiwala DL, Hushmendy SF, Yager EJ, Ruggiero EA, Crawford DR. Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration. J Alzheimers Dis. 2012; March 29 epub ahead of print.
Fuller DH, Rajakumar P, Che JW, Narendran A, Nyaundi J, Michael H, Yager EJ, Stagnar C, Wahlberg B, Taber R, Haynes JR, Cook FC, Ertl P, Tite J, Amedee AM, Murphey-Corb M. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques. PLoS One. 2012; 7(3):e33715.
Freeman ML, Burkum CE, Yager EJ, Woodland DL, Blackman MA. De novo infection of B cells during murine gammaherpesvirus 68 latency. J Virol. 2011, Oct; 85(20):10920-10925.
Kohlmeier JE, Reiley WW, Perona-Wright G, Freeman ML, Yager EJ, Connor LM, Brincks EL, Cookenham T, Roberts AD, Burkum CE, Sell S, Winslow GM, Blackman MA, Mohrs M, Woodland DL. Inflammatory chemokine receptors regulate memory CD8+ T cell contraction and memory generation following infection. J Exp Med. 2011; 208(8):1621-1634.
Yager EJ, Stagnar C, Gopalakrishnan R, Franchini A, Narendran A, Fuller JT, Fuller DH. Particle-mediated DNA vaccines against seasonal and pandemic influenza viruses elicit strong mucosal antibody and T cell responses in the lung. Procedia in Vaccinology. 2010; 3:2-11.
Loudon P.T., Yager EJ, Lynch DT, Narendran A, Stagnar C, Franchini AM, Fuller JT, White PA, Nyaundi J, Wiley CA, Murphey-Corb M, Fuller DH. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. PLoS One. 2010, Jun 8; 5(6):e11021
Yager EJ, Kim IJ, Freeman ML, Lanzer KG, Burkum CE, Cookenham T, Woodland DL, Blackman MA. Differential impact of ageing on cellular and humoral immunity to a persistent murine gamma-herpesvirus. Immun Ageing. 2010, Feb 2; 7:3.
Yager EJ, Dean HJ, Fuller DH. Prosepects for developing an effective particle-mediated DNA vaccine against influenza. Expert Rev Vaccines. 2009; 8(9):1205-1220.
Yager EJ, Szaba FM, Kummer LW, Lanzer KG, Burkum CE, Smiley ST, Blackman MA. gamma-herpesvirus-induced protection against bacterial infection is transient. Viral Immunol. 2009;22(1):67-72.
Maue AC, Yager EJ, Swain SL, Woodland DL, Blackman MA, Haynes L. T-cell immunosenescence: lessons learned from mouse models of aging. Trends Immunol. 2009; 30(7):301-305.
Ahmed M, Lanzer KG, Yager EJ, Adams PS, Johnson LL, Blackman MA. Clonal expansions and loss of receptor diversity in the naive CD8 T cell repertoire of aged mice. J Immunol. 2009;182(2):784-792.
Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008; 205(3):711-723.