DF/HCC members awarded grants amid tight funding environment
The NIH continues to recognize DF/HCC as a leader in cancer research by awarding funding to a number of our research initiatives. Recently, these awards included three program project grants (P01):
Antigen presentation in human autoimmune diseases
PI: Kai Wucherpfennig, MD, PhD (DFCI)
This project focuses on the mechanisms of antigen presentation and T cell recognition in human autoimmune diseases. The overarching hypothesis is that the development and progression of autoimmune diseases are controlled by specialized populations of antigen presenting cells that serve distinct roles in tolerance induction versus propagation of autoimmunity. Specific aims are: define the mechanisms of immunological synapse formation by examining the kinetics of synapse formation, the recruitment of key signaling molecules, the duration of signaling and the mechanisms that terminate signaling by TCR internalization; examine how these changes quantitatively modify the contribution of particular signaling pathways in self-reactive versus anti-viral T cells, with the goal of identifying signaling molecules that are critical for the activation of self-reactive T cells but dispensable for anti-viral T cells; and examine whether tolerance can be induced for such T cells by targeted delivery of the self-peptide via an antibody-peptide fusion protein to lymph node stromal cells specialized in peripheral tolerance.
Hematopoietic stem cell commitment
PI: Daniel Tenen, MD (BIDMC)
A complex interaction of different processes plays a critical role in the development of hematopoietic lineages, and among the most important are the controls of hematopoietic stem cell (HSC) commitment. Understanding this process is critical to understanding HSC function and self-renewal, and ultimately being able to manipulate HSC for therapeutic purposes and understand disease processes which involve HSC, like leukemia. This program consists of four interrelated projects that focus on some aspect of HSC regulation and function.
Statistical informatics for cancer research
PI: Louise Ryan, PhD (DFCI)
This program will tackle a series of problems motivated by the analysis of high dimensional data arising in population-based studies of cancer. Project 1 focuses on spatio-temporal modeling of disease count data collected for administrative areas. The proposed methods address issues associated with administrative boundaries changing over time, sparse disease counts, spatial confounding, and heavy computational burdens for large data sets. Project 2 is also motivated by spatially-indexed data related to cancer incidence and mortality, but the emphasis is on population surveillance and spatial cluster detection. Project 3 focuses on methods for the analysis of very high dimensional genomic and proteomic biomarkers. Extensions to spatially indexed genomic data are also considered in Project 3.