Project Details
Description
While many strides have been made in the study of human immune responses, numerous knowledge gaps still
remain. Many infections and immune-mediated diseases are localized to specific tissues, or organs but little is
known about tissue/organ-specific immunity. A major overall goal of this CCHI program to this end is to
understand memory CD8 T cells differentiation in the blood, tissues and organs. We have added Dr. Donna
Farber to our CHHI-EVC team this cycle. She has established a unique human tissue resource enabling
acquisition of blood and various tissues from deceased organ donors, we will therefore analyze virus-specific
memory CD8 T cells in various tissues of deceased organ donors and address questions regarding the anatomic
distribution and the epigenetic, transcriptional and phenotypic profile of virus-specific CD8 T cells elicited by live-
attenuated virus vaccines and with minimal risk of antigenic re-exposure. The second major goal of this program
is to elucidate the molecular mechanisms of “trained immunity” after YFV vaccination and viral infection to and
harness this knowledge for future development of new classes of vaccines and immunotherapies. We will
address the following questions. To what extent is so called “innate memory” caused by the effects of an ongoing
adaptive immune response (for example, via paracrine signaling), versus a cell intrinsic property of innate cells,
similar to the classic phenomenon of immune memory exhibited by memory T or B cells? Is there an enhanced
response of DCs and monocytes, (similar to a memory response in the adaptive immune system), during
secondary vaccination or infection? If so, what are the cellular and molecular mechanisms involved? Finally, the
third overall goal is to identify signaling and transcription factor (TF) networks associated with T memory cell
differentiation and survival and quantify how these networks change with age. This will be achieved in the
following projects: Project 1: Immune memory (Ahmed, Hellerstein, Farber); Project 2: Innate immunity
(Pulendran, Hellerstein), and Project 3: Immune senescence (Goronzy, Greenleaf). Supported by the following
Core A: Adminstration (Ahmed); Core B: Single cell and integrative genomics (Bosinger, Greenleaf); Core C:
Clinical and biostatistical (Edupuganti, Kulkanya, Yu).
Status | Active |
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Effective start/end date | 9/30/03 → 4/30/24 |
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