Dr. Blair [Illini 4000 Fellow] aims to address a key bottleneck in drug discovery by developing a generalizable strategy for synthesis of complex natural products to be used as therapeutics. Small molecules created by nature (natural products) often possess extraordinary functional potential and have led to many transformative human medicines. Unfortunately, despite important progress in the field of natural product synthesis, the methods available for synthesizing such complex natural products are typically too slow for practical drug discovery and development. He proposes to break down complex natural products into simple building blocks, which can then be iteratively assembled through automation to generate natural products.

Dr. Blanton is focusing on the contributions of the X and Y chromosomes to immune cell gene expression and function. Since the immune system plays a crucial role in tumor biology and cancer treatment, this work will help illuminate differences between cancer susceptibility, progression, and treatments in men and women.

Dr. Belyy studies how cancerous cells bypass normal signaling pathways and continue to grow uncontrollably, instead of either repairing themselves or dying in response to “unfolded protein stress.” Under these conditions, normal cells have evolved to sense this type of stress and either fix the problem or, if the fix fails, die in a controlled manner to protect the rest of the organism. He plans to use recent advances in light-activated protein engineering to study unfolded protein-mediated cell death and hopefully understand how cancerous cells are able to escape their programmed fate. These studies will potentially inform the next generation of cancer therapies targeting molecules involved in responding to the buildup of unfolded proteins.

Dr. Boettiger uses new high-resolution imaging technology to visualize the spatial arrangement of the genome in individual cells. Alterations in the physical structure of the genome affect gene expression and cell behavior. He aims to explain how mutations and genome structure changes give rise to malignancy and treatment resistance in cancer cells.

Dr. Bonifant is studying how best to direct the immune system to combat acute myeloid leukemia (AML), a blood cancer of both children and adults. By specifically directing T immune cells to AML, she hopes to make therapy stronger and more effective, while also reducing toxicity. She is exploring the activity of T cells targeting multiple AML-specific antigens that do not affect normal cells. The ultimate goal of the work is to develop new strategies to treat AML.

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. Brooks is analyzing cancer genome sequence data to identify DNA mutations that affect RNA splicing, a form of gene processing and regulation. By characterizing these mutations, her work will provide further understanding of the role of splicing alterations in cancer as well as insight into the functional consequences of cancer mutations.

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. Cai is interested in whether the state of cellular “protein crowdedness” can be used to differentiate healthy normal cells from cancer cells. Having the ability to monitor protein crowding and protein-folding landscapes within cells could provide a valuable “readout” for changes in metabolism and the overall health or dysfunction of cells.