Jennifer Snyder-Cappione, Ph.D.

Research Assistant Professor, MicrobiologyCappione
Director, Flow Cytometry Core Facility
650 Albany Street, X325
(617) 414-5225
cappione@bu.edu

B.S.     Brandeis University
Ph.D.  University of Rochester Medical Center

My current research interests include: (1) improving ex vivo methodologies to help determine the functional interchanges between cell subsets in vivo that dictate an fate of a diseased site (e.g. tumor) and its impact on surrounding areas (2) investigating the differentiation potential and lineage relationships of iNKT cell subsets, and (3) elucidating the steps of immune cell exhaustion, the diversity of an exhausted, antigen-specific immune repertoire, and its role in the progression of chronic diseases.

(1) Within a given microenvironment, complex functional exchanges occur between cells.  Attempts to define the roles of cellular subsets within a site, such as a solid tumor, using surface markers and/or secretion of a small number of functions (as current methods allow) are not reflective of in vivo biology. Elucidating the composite functional activity of individual cells from within disease sites, such as solid tumors and granulomas, will provide new insight into the mechanisms and distinct cellular subsets that impact both its progression and response to therapeutic interventions.

(2) iNKT cells are a unique T cell subset that are believed to bridge the innate and adaptive arms of an immune response.  They have been implicated as key factors in the prevention of some autoimmune diseases, as well as potent effector cells in the containment of viral and bacterial infections, including HIV.  Conversely, many studies report that iNKT cells have deleterious effects on the host during autoimmune and infectious diseases.  This seemingly conflicting data is likely due to nuances of the differentiation and selective exertion of effector functions by subsets of this cell type that remain poorly understood.  Further investigation of the lineage relationships and functional differences between the major iNKT subsets could lead to a deeper understanding the diverse impact of the iNKT cell compartment on disease progression.

(3) During many chronic diseases, antigen-specific CD8+ T cells exhibit low functional activity, express inhibitory receptors, and have little/no proliferative capacity; this reversible state is identified as ‘exhaustion’.  Clinical trials of therapies that block inhibitory receptor signaling on T cells in cancer patients have been ongoing for several years.  Recently, trials targeting the PD-1/PD-1L pathway in many advanced malignancies (including melanoma, non-small cell lung cancer, and renal carcinoma) have reported groundbreaking results, with some patients exhibiting 100% tumor reduction. These are arguably the most promising cancer immunotherapy trial results to date.  Elucidation of both the complexity of the exhaustion process and the diversity of the exhausted immune cell repertoire in chronic diseases such as cancer will lead to more targeted, effective therapeutics.

Representative Publications

  1. Snyder-Cappione J.E., D.F. Nixon, J.C. Chi, M.T. Nguyen, C.K. Kirby, J.M. Milush, and L.L. Koth. 2013. Invariant natural killer T (iNKT) cell exhaustion in sarcoidosis. Eur. J. Immunol. 43:2194-205 2013. PMID: 23661497
  2. Tincati C, A.J. Cappione, and J.E. Snyder-Cappione. 2012. Distinguishing Latent from Active Mycobacterium Tuberculosis Infection Using Elispot Assays: Looking Beyond Interferon-gamma. Cells 1:89-99. PMID: 24710416
  3. Snyder-Cappione J.E., C. Tincati, I.G. Eccles-James, A.J. Cappione, L.C. Ndhlovu, L. Koth, and D.F. Nixon. 2010. A comprehensive ex vivo functional analysis of human NKT cells reveals production of MIP-1 alpha and MIP-1 beta, a lack of IL-17, and a Th1-bias in males. PLoS One 5:e15412. PMID: 21082024
  4. Milush J.M., B. Long, J.E. Snyder-Cappione, A.J. Cappione, V.A. York, L.L. Lanier, J. Michaëlsson, and D.F. Nixon. 2009. Functionally distinct subsets of human NK cells and monocyte/DC-like cells identified by co-expression of CD56, CD7, and CD4. Blood 114:4823-31. PMID: 19805616
  5. Snyder-Cappione J.E., C.P. Loo, K.I. Carvalho, C. Kuylenstierna, S.G. Deeks, F.M. Hecht, M.G. Rosenberg, J.K. Sandberg, E.G. Kallas, and D.F. Nixon. 2009. Lower cytokine secretion ex vivo by NKT cells in HIV-infected individuals is associated with higher CD161 expression and duration of infection. AIDS 23:1965-70. PMID: 19590406
  6. Rebhahn J.A., C. Bishop, A.A. Divekar, K. Jiminez-Garcia, J.J. Kobie, F.E. Lee, G.M. Maupin, J.E. Snyder-Cappione, D.M. Zaiss, T.R. Mosmann. 2008. Automated analysis of two- and three-color fluorescent Elispot (Fluorospot) assays for cytokine secretion. Comput. Methods Programs Biomed. 92:54-65. PMID: 18644656
  7. Snyder-Cappione J.E., D.F. Nixon, C.P. Loo, J.M. Chapman, D.A. Meiklejohn, F.F. Melo, P.R. Costa, J.K. Sandberg, D.S. Rodrigues, and E.G. Kallas. 2007. Individuals with Pulmonary Tuberculosis have lower levels of circulating CD1d-restricted NKT cells. J. Infec. Dis. 195:1361-1364. PMID: 17397008
  8. Moll M., J. Snyder-Cappione, G. Spotts, F.M. Hecht, J.K. Sandberg, and D.F. Nixon. 2006. Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2. Blood 107:3081-3083. PMID: 16368878
  9. Snyder-Cappione J.E., A.A. Divekar, G.M. Maupin, X. Jin, L.M. Demeter, and T.R. Mosmann. 2006. HIV-Specific Cytotoxic Cell Frequencies Measured Directly Ex Vivo by the Lysispot Assay Can Be Higher or Lower Than the Frequencies of IFN-{gamma}-Secreting Cells: Anti-HIV Cytotoxicity Is Not Generally Impaired Relative to Other Chronic Virus Responses. J. Immunol. 176:2662-2668. PMID: 16456029
  10. Snyder, J.E. and T.R. Mosmann. 2003. How to “spot” a real killer. Trends Immunol. 24:231. PMID: 12738412
  11. Snyder J.E., W.J. Bowers, A.M. Livingstone, F.E. Lee, H.J. Federoff, and T.R. Mosmann. 2003. Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing. Nat. Med. 9:231-235. PMID: 12539041
  12. Snyder J.E., N.M. Filipov, P.J. Parsons, and D.A. Lawrence. 2000. The efficiency of maternal transfer of lead and its influence on plasma IgE and splenic cellularity of mice. Toxicol. Sci. 57:87-94. PMID: 10966514