Anjon Audhya

Dysregulated cell proliferation underlies all forms of oncogenesis. In particular, chromosomal aberrations sometimes enable a subpopulation of cells to grow in an uncontrolled fashion, leading to tumor formation. Such defects are often associated with changes in cellular signal transduction pathways, such as the Ras-Raf-MEK-ERK kinase cascade, which promotes cell survival and growth. Notably, upregulated ERK activity has been implicated in numerous malignancies, including papillary thyroid carcinoma, pancreatic cancer, colorectal cancer, melanoma, and lung cancer. During the course of their studies, members of the Audhya laboratory demonstrated that two oncogenic fusion proteins, TFG-NTRK1 and TFG-ALK, created by distinct chromosomal translocation events, localize to subdomains of the endoplasmic reticulum (sites of COPII vesicle formation) and dramatically upregulate ERK activity. Using phosphoproteomic approaches, they are mapping downstream effectors of TFG-NTRK1 and TFG-ALK that simultaneously drive cell transformation and regulate vesicle secretion. By altering membrane transport in the early secretory pathway, TFG fusion proteins may modulate cargo export, potentially enhancing the secretion of growth factors that help to sustain a rich tumor microenvironment.

Our laboratory is committed to understanding fundamental mechanisms by which membrane proteins, lipids, and other macromolecules are transported throughout eukaryotic cells. To do so, we take advantage of numerous interdisciplinary approaches, including biochemistry, structural biology, biophysics, genetics, molecular biology and high resolution fluorescence and electron microscopy.

Additionally, we use a variety of experimental systems, ranging from simple animal models (e.g. Caenorhabditis elegans) to human induced pluripotent stem cells (iPSCs). We also aim to recapitulate individual steps of membrane transport in vitro, using recombinant proteins and chemically defined lipids. Our ultimate goal is to identify the regulatory pathways that control membrane deformation, which enable vesicle formation in the endosomal and secretory systems. Although basic research is the cornerstone of our program, we also seek to define pathomechanisms that underlie human disease, focusing on the impact of mutations in key trafficking components that lead to cancer, neurodegeneration, asthma, and diabetes.