Mammalian cellular metabolism is a dynamic process that consists of thousands of interconnected reactions and regulatory interactions. While the architecture of metabolic networks is defined by the genome, actual metabolic activity (i.e. metabolic flux) through the pathways varies greatly. Dynamic reprogramming of metabolism enables cells to meet metabolic needs associated with specific cellular states and cellular functions (such as supporting proliferation or activating immune function), and adapt to changes in the environment. The overarching goal of our research is to understand how mammalian cellular metabolism is reprogrammed in response to changes in the environment and cellular state, and how activities in key metabolic pathways can in turn affect cell function. To study this, we combine systems biology approaches, especially fluxomics and metabolomics, with computational modeling and biochemical and genetic techniques.
Tumor-stroma interactions; heparan sulfate proteoglycans in cancer.
Extracellular modulators of cellular behaviors in development, homeostasis, and disease
The Gumperz lab studies human innate T lymphocytes, with a particular focus on a subset called Natural Killer T (NKT) cells. NKT cells are able to affect the functions of many other types of immune cells, and in so doing they can markedly influence the outcome of immune responses. Because of this, and because they are activated by conserved antigens, NKT cells are of interest as a human lymphocyte population that could be harnessed clinically for immunotherapeutic strategies.
What interests us about NKT cells is that they can become activated by self lipids, which means that they can perform functions even when there is no infectious challenge, and they can amplify immune responses without requiring the presence of a specific foreign antigen. One of the central questions my lab is addressing is to understand how this autoreactivity contributes to inflammatory responses and immune regulation. We are investigating these questions at the molecular and cellular levels, and also in the context of larger immunological processes such as graft-vs-host disease that occurs after transplantation of hematopoietic stem cells, and immune responses during Epstein-Barr virus infection.
Tumors are often heterogeneous with respect to many features. My research focuses on identifying sources of heterogeneity and determining how such heterogeneity impacts prevention and treatment. Novel concepts are being tested with a unique experimental platform consisting of recently developed animal models and state-of-the-art imaging. The results could potentially shift current paradigms in cancer biology.
1. Genomics and Molecular Imaging of Lung-Brain Metastasis
2. Defining the functional significance of bromodomain containing proteins in pan-cancer studies.
The capacity for complex tissue regeneration is unevenly distributed across species. Unlike human, zebrafish possess a remarkable potential to regenerate tissues such as amputated appendages and damaged heart muscles. Interest of my laboratory is to understand how and what genetic and epigenetic factors control tissue regeneration using adult zebrafish as a model system.
Understanding the molecular regulation and pathogenesis of the human herpesvirus; Epstein-Barr virus (EBV)