Sean Leng, MD PhD, has demonstrated great promise, and unsurpassed determination, to become a leader in clinical / translational aging research. He has had advanced training in Immunology and Molecular Virology, Cytokine Research, and Internal Medicine. After a clinical and research fellowship in Geriatric Medicine and Gerontology at Johns Hopkins, he was recruited to its faculty as an Instructor in 2002 and was promoted to Assistant Professor of Medicine in 2003. He is a recipient of a short-term R21 from NIA and an internal research award at Johns Hopkins. Dr. Leng has strong mentorship from geriatrician and epidemiologist Dr. Linda Fried, Professor and Director of the Division of Geriatric Medicine and Gerontology and Center on Aging and Health, and from immunologist Dr. Noel Rose, Professor and Director of Center for Autoimmune Disease Research. They will provide him with extensive resources and a stimulating interdisciplinary environment to launch his independent academic career in translational aging research. ? ? Dr. Leng's research interest is in frailty, a common geriatric syndrome characterized by dysregulations in multiple physiologic systems and increased vulnerability to stressors, including infections, that result in severe adverse health outcomes in older adults. Based on the preliminary findings from Dr. Leng's current research, this project proposes a pilot influenza immunization study in community-dwelling frail and age-matched non-frail older adults. With this clinically well-established in vivo immune challenge, we will characterize immune dysregulation of frail older adults and translate its implications in the context of clinical import under the following specific aims: 1) Determine whether frail older adults have impaired humoral immunity measured by viral-specific antibody tilers; 2) Determine whether frail older adults have impairment in vaccine-induced cell-mediated immunity (CMI) measured by number of antigen-specific CD4+ and CD8+ T cells, intracellular production of IFN-y and IL-2, and cytotoxic T lymphocyte (CTL) function. Dr. Leng will also evaluate the relationship of pre-vaccination number of specific T cell phenotype, CD8+CD28-T cells, with vaccine-induced CMI; 3) To delineate whether vaccinated frail older adults have increased rate of influenza infection and its complications (pneumonia, hospitalization, and death), compared to non-frail controls, during the post-vaccination season. As our initial translational effort, this project will improve our ability to evaluate and strengthen immune function, and ultimately prevent related adverse health outcomes, including influenza infection and its devastative complications, for frail older adults. ? ? Dr. Leng's dual training in clinical geriatric medicine and basic immunology/molecular virology and cytokine research, strong mentorship, carefully designed career development program, supportive environment, and novel research plan will give him the experience and tools that he needs to develop into a highly successful, independent physician/geriatrician-scientist. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG028963-02
Application #
7283134
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
Program Officer
Fuldner, Rebecca A
Project Start
2006-09-01
Project End
2011-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$199,174
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Yao, Xu; Hamilton, Robert G; Weng, Nan-ping et al. (2011) Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine 29:5015-21
Yao, Xu; Li, Huifen; Leng, Sean X (2011) Inflammation and immune system alterations in frailty. Clin Geriatr Med 27:79-87
Leng, Sean X; Tian, Xinping; Matteini, Amy et al. (2011) IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing 40:475-81
Leng, Sean X; Li, Huifen; Xue, Qian-Li et al. (2011) Association of detectable cytomegalovirus (CMV) DNA in monocytes rather than positive CMV IgG serology with elevated neopterin levels in community-dwelling older adults. Exp Gerontol 46:679-84
Leng, Sean X; Qu, Tao; Semba, Richard D et al. (2011) Relationship between cytomegalovirus (CMV) IgG serology, detectable CMV DNA in peripheral monocytes, and CMV pp65(495-503)-specific CD8+ T cells in older adults. Age (Dordr) 33:607-14
Leng, Sean X; Tian, Xinping; Liu, Xiaohong et al. (2010) An international model for geriatrics program development in China: the Johns Hopkins-Peking Union Medical College experience. J Am Geriatr Soc 58:1376-81
Qu, Tao; Yang, Huanle; Walston, Jeremy D et al. (2009) Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine 46:319-24
Leng, Sean X; Hung, Will; Cappola, Anne R et al. (2009) White blood cell counts, insulin-like growth factor-1 levels, and frailty in community-dwelling older women. J Gerontol A Biol Sci Med Sci 64:499-502
Qu, Tao; Walston, Jeremy D; Yang, Huanle et al. (2009) Upregulated ex vivo expression of stress-responsive inflammatory pathway genes by LPS-challenged CD14(+) monocytes in frail older adults. Mech Ageing Dev 130:161-6
De Fanis, Umberto; Wang, George C; Fedarko, Neal S et al. (2008) T-lymphocytes expressing CC chemokine receptor-5 are increased in frail older adults. J Am Geriatr Soc 56:904-8

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