A human epithelial cell undergoing division. A rapidly dividing cancer cell must coordinate the equal distribution of several diverse cellular components to each of its daughter cells. Proper segregation of the mitochondrial network requires the small GTPase RalA and its effector RalBP1. In this cell, mitochondria are stained with MitoTracker dye (red), actin is stained with phalloidin (green) and DNA is stained with DAPI (blue). Courtesy of the Kashatus Lab.
Understanding human cancers and developing strategies for treating specific cancers has been at the forefront of biology for many decades. The nature of investigations into this area continues to evolve as we understand more and face newer challenges. The Cancer Biology faculty within MIC focus on cutting-edge basic cancer research as well as exposure to state-of-the-art clinical cancer patient care and treatment. Areas of research include signaling in cancer cells, mechanisms of genetic and cellular perturbations that predispose to cancer, influence of tumor microenvironment in regulating breast and pancreatic cancers, brain tumors such as gliomas, and immunotherapies.
Examples of projects currently undertaken by our faculty include: (a) Dr. Amy Bouton studying how altered signaling in tumor cells and the tumor microenvironment can influence tumor progression; (b) Studies of Dr. David Kashatus on how the dynamics of mitochondrial fission and fusion within the tumor cells influence their proliferation; and (c) Studies of Dr. Roger Abounader on how c-Met and PTEN regulate brain tumors.
Investigations in Cancer Biology by our faculty use cutting-edge methodologies to probe many different questions related to tumor initiation, progression and therapies. For example, Dr. Tom Parsons is devising methodologies to modify the extracellular matrix with the goal of altering the behavior of pancreatic cancer cells; Dr. Ann Beyer is using trafficking models of automobiles to understand how polymerases move on the DNA; Dr. David Brautigan is using novel approaches in enzymology, genomics, and genetics to study how phosphatases control cell cycle and tumor cell proliferation. The investigators in Cancer Biology use a variety of genetically engineered tumor mouse models, along with state-of-the-art microscopy, including two-photon and electron microscopy. Since cancer therapeutics is a major focus of the UVA School of Medicine, there is substantial interaction between faculty members addressing basic questions in cancer biology and clinicians in the UVA Health System (examples include those of Drs. Sally Parsons, Jill Slack-Davis and Susan Modesitt addressing ovarian cancers as part of the Women’s Oncology group, Drs. Engelhard and Craig Slingluff addressing tumor immunotherapy/peptide vaccines for melanomas). In addition to providing an exciting way to both ask and address fundamentally important questions in cancer biology, such interactions provide an intellectually stimulating training environment for students and post-doctoral fellows.
It is important to recognize that many of the faculty whose research focuses on cancer biology collaborate extensively with those working in immunology and infectious disease. Such interactions broaden the scope of the questions that can be asked and enrich the intellectual rigor and depth that can be achieved in addressing the key scientific problems.