Congratulations to the 2013 February recipients.
Winners from applications received before the April 30 deadline will be announced by May 10.
Adaptive has selected 4 winners for the Young Investigator Award. Each recipient will receive $5,000 to use for sequencing to assist in his/her research in immunology. The next group of winners will be chosen from applications due July 31. Click here to apply »
Alan Watson, Ph.D., University of Pittsburgh
Research Summary: T cell responses elicited by the live-attenuated Yellow Fever Virus (YFV) Vaccine play a role in protecting the host against infection with wild-type (wt)YFV in our mouse model; however, non-vaccinated mice succumb to disease following wtYFV infection despite eliciting surprisingly high numbers of polyfunctional T cells. I will use the immunoSEQ system to compare the clonotypic diversity of T cells elicited following vaccination or infection with wtYFV and ask whether differences in T cell repertoire may explain immune control of the YFV vaccine and immune evasion by wtYFV.
Sven Malchow, Ph.D., University of Chicago, Dept. of Pathology
Research Summary: In a recent study, we demonstrated that the thymic development of some naturally occurring Foxp3+ regulatory T cells (Tregs) is dependent on the transcriptional regulator Aire (autoimmune-regulator). Aire expression in the thymus drives the ectopic expression of peripheral tissue self antigens, and Aire-deficiency in mice and humans results in multi-organ autoimmunity. The relative contribution of Aire-dependent Tregs to the peripheral Treg pool is unknown. I will use the immunoSEQ technology to elucidate the prevalence of Aire-dependent Tregs within the peripheral repertoire by determining the extent of TCR β chain repertoire overlap between CD4+Foxp3neg and CD4+Foxp3+ T cell populations derived from wild-type and Aire-deficient mice. The results of this study are anticipated to provide new insights into the antigen specificities and development of Tregs, with implications for the treatment of autoimmunity and cancer.
Marta Pasikowska, King’s College London
Research Summary: We would like to perform analysis of TCR beta repertoire diversity of CD4+ T cell found in non-reactive lymph nodes from healthy individuals. These studies would broaden our understanding of the dynamics of T cell circulation and retention in lymph nodes in normal health. In addition, they would serve as reference point for our studies looking into the changes in the TCR beta diversity in chronic lymphocytic leukaemia and will hopefully help other researchers to interpret the results of their studies on TCR diversity in other disease-involved lymph nodes.
Michela Bardini, Centro Ricerca Tettamanti University of Milan Bicocca
Research Summary: Acute lymphoblastic leukemia with the Mixed-Lineage Leukemia gene rearrangement occurring within the first year of age (MLL+ Infant ALL) is a very aggressive disease, associated to an overall dismal prognosis, in which the MLL gene rearrangement is the pre-natal and powerful genetic event driving and hastening the leukemia initiation.
By clonal studies in relapsed patients, and serial xeno-trasplantation assays into immunedeficient NOD/SCID mice, we have uncovered an exceptional clonal diversity and competition/selection of multiple co-existing leukemic clones (as for example we have observed that dominant clones at disease presentation might persist or extinguish at relapse; whilst ‘new’ clones, which were indeed minor component of the leukemic bulk but quiescent at diagnosis, might reactivate and take over at relapse).
In the proposed study we will perform next-generation profiling of Ig/TCR gene rearrangements in order to i. further dissect the clonal composition of MLL+ leukemia and ii. follow the dynamics of competition/selection of multiple pre- existing leukemia-initiating clones during disease progression; both in paired diagnosis/relapse samples from MLL+ infant ALL patients, as well as in xenograft leukemia samples from serially transplanted mice.
2012 November Recipients
Jennifer Sims, Ph.D., Columbia University Medical Center
Research Summary: Glioblastoma multiforme (GBM) remains the most aggressive and prognostically devastating primary brain tumor, unusually persistent in the face of surgical, chemotherapeutic, radiological intervention. We are studying the links between glioma progression (and suppression) and perturbation of the T cell population within the tumor and the periphery with both human patient samples and our murine model.
Joseph Hai Oved, M.A. B.A., NYU School of Medicine
Research Summary: Recently our lab made the surprising discovery that the vast majority of known human CD4 and CD8 Mycobacterium tuberculosis antigens are conserved, leading us to hypothesize that on an evolutionary level, immune recognition may benefit the bacteria, most likely by promoting transmission. Our findings have important implications for design of a tuberculosis vaccine. Using these data and Immunoseq’s technology, I am examining the T cell receptor repertoire of activated T cells against conserved and variable Mtb antigens in tuberculin skin test positive patients. It is our hypothesis that dissection of this system and understanding the differences of the host immune response to these antigens will prove to be fruitful in framing TB vaccine development in the future.
Gaurav Gaiha, Ph.D., Ragon Institute of MGH, MIT and Harvard
Research Summary: Given recent findings implicating the role of CD8+ T cell receptor clonotypes in HIV control, we propose using the immunoSEQ platform to profile the entire TCR beta repertoire of HIV-specific CD8+ T cells from patients with known periods of controlled and progressive infection. This unique intra-patient comparative approach would provide a first in-kind perspective on the global changes in HIV-specific TCR repertoires that account for these divergent clinical presentations, ultimately guiding further development and monitoring of efficacious T cell based vaccines.
Eric Allenspach, Ph.D., Seattle Children’s Hospital
Research Summary: My project proposal is to compare the naïve B cell IgH repertoire of normal human control samples with patients with human primary immunodeficiency syndromes. Many patients have autoimmunity symptoms that may be explained by a shift in the peripheral B cell repertoire.
Taizo Nakano, M.D., Children’s Hospital Colorado
Research Summary: Neuroblastoma, the most common extracranial solid tumor in infants and young children, accounts for 15% of childhood cancer mortality. We hypothesize that T cells actively undergo clonal expansion in response to neuroblastoma and that overrepresented T cell receptor repertoire sequences will act as diagnostic and/or prognostic tools that will influence treatment decisions and lead to novel antigen discovery. Variations in the diversity of the anti-tumor immune repertoire amongst patients with stage IV neuroblastoma, between patients of low stage and high stage disease, and after the administration of induction chemotherapy will greatly expand our current understanding of neuroblastoma immunology.
2012 August Recipients
Evaggelia Liaskou, University of Birmingham, UK
Research Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease, characterized by progressive inflammation, fibrosis and destruction of the bile ducts. Studies suggest that T cells play a pivotal role in the progression of PSC disease. In this project, we propose to isolate T cells from human PSC liver tissue and matched peripheral blood and using the immunoSEQ technology to profile the human T cell receptor beta, in order to investigate the presence of specific TCRs in PSC patients that will help us understand what antigens might be able to interact with the variable regions and thus identify what causes the activation of T cells in human PSC liver.
Kyle K. Payne, Virginia Commonwealth University – Massey Cancer Center
Research Summary: Through the use of ultrahigh-throughput sequence analysis, this project proposes to determine whether the T cells of patients with breast cancer exhibit a unique molecular signature in VDJ gene recombination of the TcR Vβ following an ex vivo T cell expansion and re-programming protocol developed by our group. The existence of distinct TcR clonotypes in re-programmed T cells would provide rationale for future immunomonitoring of TcR Vβ recombination in breast cancer patients in order to predict objective responses following initial therapy.
Patrick Smith, Harvard School of Public Health
Research Summary: Co-evolution between colonic T regulatory cells (cTregs) and the gut microbiota has resulted in the use of a distinct T cell receptor (TCR) repertoire by cTregs to respond to antigens derived from commensal bacteria and maintain intestinal homeostasis and health. Using the Immunoseq Young Investigator Award, I aim to analyze the cTreg TCR repertoire of germ-free, gnotobiotic and conventionally raised mice to unravel how the microbiota affect the cTreg function and shed new light on host Treg-microbiota interactions that promote intestinal homeostasis.
Alison Smith, Tulane University
Research Summary: Obesity is a chronic inflammatory condition characterized by activation and infiltration of T cells into adipose tissues, which is an integral step in the development of associated metabolic syndromes such as diabetes. The goal of this project is to analyze the variable region of T cells in adipose tissue from obese patients with type-2 diabetes using a high-throughput sequencing method in order to better understand the role of T cells in the pathophysiology of this disease.
Patrick Hanley, Baylor College of Medicine
Research Summary: We have an ongoing clinical trial where we infuse virus-specific T cells derived from cord blood into cord blood transplant recipients. Using TCR sequencing, we are trying to determine whether the T cells that we give to the patients persist in vivo and correlate with protection or resolution of viral infections.