Dr. Bosch is studying the molecular language of cell-cell communication, an essential function of animal cells that coordinates normal tissue development and function that is frequently misregulated in many cancers. By developing novel methods to study the biological functions of an extraordinary class of intercellular messages-those that transfer directly into the interior of recipient cells-he will gain new insight into fundamental modes of cell-cell communication. His research will improve our understanding of the molecular events leading to cancer progression, leading to development of improved methods to deliver drugs into cells.

Dr. Bridges studies how bacterial cells form communities called biofilms that have particular three-dimensional architectures. He is investigating how the bacterial cell-cell communication process called quorum sensing drives the spatio-temporal gene expression patterns that govern biofilm formation. Biofilm bacteria are implicated as causal in various cancers and, furthermore, cancer patients receiving chemotherapy frequently suffer from infections caused by bacteria that rely fundamentally on biofilm formation for pathogenesis. By discovering the quorum-sensing program that bacteria execute to sculpt biofilm architectures, he hopes to contribute to the development of new strategies to interfere with formation of these bacterial communities.

Dr. Burton studies how chemical modification of histone proteins leads to changes in the structure of chromatin, the physiologically relevant form of DNA, and how misregulation of this higher-order assembly can lead to aberrant gene transcription patterns and cancer. He will use chemical biology tools to carry out precise chemistry in live cells, and determine direct causality in the downstream effects on DNA accessibility and transcription.

Dr. Caldas is investigating the mechanisms by which RNA interference (RNAi) related pathways, implicated in cancer primarily through their role in regulating gene expression, contribute to the fidelity of cell division. In addition to major changes in gene expression, a hallmark of many cancers is genome instability and chromosome loss, processes highly related to inaccurate cell division. Using C. elegans as a model system, her goal is to identify new aspects of cell division control that can be targeted for cancer therapy.

Dr. Cambier [HHMI Fellow] studies the role of cells called macrophages in mediating inflammation in immune responses to cancer. He is using the Mycobacterium marinum/zebrafish model of infection to examine misguided immune responses, many of which are shared with cancer. In particular, he proposes to study the distribution of a mycobacterial glycolipid molecule that is associated with driving macrophage activation and death, and will visualize the interactions of these glycolipids with macrophages in a living system. This new imaging approach along with the ability to manipulate host and pathogen genetics in a controlled setting will shed light on the inflammatory mechanisms driving disease. He hopes these findings will lead to new cancer therapies that modulate macrophages.

Dr. Case is establishing an in vitro experimental system to study the formation of integrin signaling complexes on model membranes. Integrins form multiprotein signaling complexes that are essential for the survival, growth, and migration of tumor cells; integrins and their associated proteins are commonly mutated or misregulated in diverse cancer types. She will elucidate the molecular interactions and physical mechanisms that regulate the assembly of  integrin complexes to potentially reveal novel strategies for disrupting integrin signaling in cancer.

Dr. Chakraborti is developing technologies to facilitate the rapid identification of individual, specific, safely targetable tumor antigens, and to engineer tumor chimeric antigen receptors (CARs) to specifically recognize and kill cancer cells within a clinically relevant timeline. Dr. Chakraborti also plans to use these technologies to investigate the role of helper T cells in enhancing the activity of anti-cancer killer T cells. These technologies, although applicable to adult cancers as well, will focus on antigens derived from pediatric cancer tissues because conventional therapies (such as chemotherapy and radiation) hold long-term health risks. 

Dr. Chiba investigates how cancer cells evade a patient's immune system. Though checkpoint blockade therapies have expanded the options for cancer patients, only a fraction of those treated actually benefit due to the emergence of immune resistance. Dr. Chiba will use molecular and genetic approaches to dissect the ways that cancer-associated mutations alter the tumor environment to avoid immune surveillance. The aim of this research is to improve the efficacy of cancer immunotherapy so many more patients will benefit.

Dr. Chung is focusing on the biology of fat storage organelles called lipid droplets (LDs). Many cancer cells are characterized by an increased number of LDs, and this accumulation has been proposed to be pathogenic. Key questions of LD biology remain unanswered, limiting the potential for therapeutic intervention. She will combine various imaging technologies and biochemical approaches to elucidate the molecular architecture of initial LD formation and its regulation.

Dr. Chung is developing a new engineering approach to create intelligent and tenacious T cells with durable anti-tumor activity. Her aim is to create enhanced T cells that will infiltrate tumors, kill cancer cells, and persist long-term to prevent recurrence. Dr. Chung will use cutting-edge, multi-disciplinary approaches, including bioinformatics, protein and genetic engineering, and tumor immunology, to design a synthetic T cell differentiation pathway. This T cell reprogramming platform has the potential to transform cellular immunotherapies (such as CAR T) into "smarter" cells that target cancer with persistence and enhanced potency.