Dr. Hung focuses on a central question in cell biology: how gene expression is spatially and temporally regulated to give rise to cell types and functions. Historically, the ribosome has been viewed as a molecular machine of invariant composition that passively and constitutively translates mRNA to protein. She is studying how phosphorylation of ribosomal components may endow ribosomes with specificity for certain transcripts and unique cellular functions. This work will also provide insight into how ribosome-mediated gene expression may play a role in cellular transformation for many different cancers, and in particular, lymphomagenesis.

Dr. Hussmann is studying how translation is regulated in healthy cells and how this regulation goes awry in disease. Cells control protein abundance by modulating how frequently messenger RNAs are translated by ribosomes, but the mechanisms that determine how densely ribosomes are packed onto each individual transcript are poorly understood. He is developing experimental approaches to produce transcriptome‐wide single‐molecule measurements of ribosome density in order to advance this understanding. These approaches will provide insights into the the key role that this process plays in the development and progression of many cancers.

The uncontrolled growth and metastasis of cancer cells is driven by changes in the genes expressed by these cells, relative to cells in healthy tissue. Understanding these gene expression changes provides key insights into the behaviors of cancer cells and guides the design of anti-cancer therapies.

Dr. Ingolia is studying a cellular process called translation, which generates protein from RNA. Important gene expression changes result from differences in the translation of mRNAs into functional proteins, rather than the abundance of these mRNAs in the cell. He has developed innovative techniques to comprehensively profile translation in cells and proposes to apply this approach to understand the gene expression differences between normal and cancerous cells. These gene expression changes will reveal distinctive features of cancer cells that explain their pathological behavior and potentially expose new vulnerabilities of these cells that could be targeted to treat cancer.

Dr. Jaeger is investigating how a protein called the Heat Shock Transcription Factor 1 (HSF1), a potent pro-survival transcription factor, orchestrates changes in the three-dimensional architecture of chromosomes to activate tumor supportive gene expression programs in diverse cancer types. Increasing evidence suggests that the three dimensional architecture of chromosomes can influence the unique gene expression programs that support tumor growth. He aims to determine how gene expression is significantly altered in cancer cells when compared to normal cells.

Dr. Janetzko studies G protein-coupled receptors (GPCRs), a class of membrane-embedded proteins that relay signals about hormone and neurotransmitter binding to the inside of the cell. Several types of cancer cells hijack these proteins by keeping them in an active state (constitutively turned “on”) in order to promote their growth and allow them to metastasize. The activated GPCR often becomes a target for another set of proteins, called GRKs (GPCR kinases). GRKs chemically modify active receptors, which changes the type of signals the GPCR sends and simultaneously marks them to be turned off. His research will use structural and biophysical methods to understand how activated GPCRs are recognized by GRKs, and how these kinases might be exploited as new therapeutic targets in cancer.

Tumors evade the immune system by suppressing the function of T cells otherwise capable of destroying cancer cells. These T cells develop in lymph nodes - specialized tissues that control responses against cancer, infection, and other disease. As T cells become activated against tumors, the cells differentiate and proliferate at much slower rates. This decreased proliferation dramatically reduces the effectiveness of anti-tumor immune responses. 

Dr. Jewell is uniquely trained in both immunology and materials science. He is harnessing bioengineering, immunology, and polymer design to create degradable vaccine "depots" in lymph nodes. The goal is to use these depots to control how T cells develop, promoting a cell fate specific for attacking tumors that also maintains the ability to proliferate at the extremely high rates needed to clear existing tumors and protect against regrowth. This is the first time these ideas have been explored, and the findings from his research will support development of a new class of cancer vaccines that could clear existing tumors and prevent relapse.

Dr. Ji studies the function of a critical ATPase protein called p97 in an important cellular process called protein degradation, which regulates proteins and can promote cancer cell proliferation and survival. His goal is to understand the molecular mechanism of how p97 functions. A better understanding of p97 could ultimately benefit the development of anti-cancer drugs based on p97 inhibition.

Dr. Jiang [Merck Fellow] is studying the CRISPR-Cas system, which has been adopted as a robust and versatile platform for genome engineering in human cells as well as other experimental systems. He aims to use a combination of biochemical experiments, mutagenesis, and biophysical approaches to investigate the detailed molecular mechanism of RNA-guided DNA targeting and recognition by CRISPR-Cas9. The results of this research will provide a fundamental understanding of the Cas9 enzyme family and will support its use for site-specific genetic control, including gene therapies against cancers.

Many diseases could be cured if the power of our own immune systems could be harnessed. For cancer, the theory of "cancer immunoediting" provides a hypothesis for how tumors escape detection by the immune system. 

Dr. Jiang, a biomedical engineer, works at the interface of systems biology, genomics, and immunology. Her lab is developing a single cell-based integrated technological approach to challenge this theory. She will profile the immune system repertoire for antigen specificity, receptor gene sequences, and cellular function-related gene expression. Her approach may provide explanations for why and how the immune system tolerates tumors. Her proposed study may result in a paradigm shift that could improve cancer immunotherapies and also revolutionize health care with new personalized immune metrics for early disease detection and targeted therapy.

Dr. Kang aims to identify mechanisms that eliminate unneeded cells in the brain. During animal development, extra neurons and neuronal connections are produced, but these unneeded neurons are selectively “eaten” by glia (another type of cell in the brain) in a process called phagocytosis. He will use the nervous system of the fruit fly Drosophila melanogaster as a model system to perform rapid genetic screens and cell type-specific manipulations, allowing him to quickly find new mechanisms that regulate phagocytosis.  Understanding how cells are targeted for phagocytosis during development will help us learn how to harness these targeting mechanisms to eliminate cancer cells for therapeutic purposes. This research will also help to understand how cancer cells evade immune detection and clearance, and may aid in the development of new kinds of cancer treatments.