Dr. Hirschi is creating a tool to investigate specific glutamate receptor subpopulations and elucidate their role in cancer mechanisms. Glutamate receptors on neurons are involved with learning and memory in a time- and tissue-specific manner and abnormal function can lead to cancer. Detailed understanding of how glutamate receptors work may provide insight into new therapies for cancers ranging from gliomas to peripheral malignancies, such as pancreatic cancer.

Dr. Hu is focusing on developing small molecule inhibitors to regulate the activity of Gαs, a subunit of the stimulatory G protein, which is encoded by the GNAS gene. Activating mutations of GNAS have been revealed to contribute to progression and metastasis of several kinds of cancers. About 64% of these mutations result in a single variant called R201C, which keeps Gαs in a constitutively active state. His goal is to design and synthesize small molecules to specifically inhibit the abnormally activated Gαs (R201C). Such inhibitors would be promising tools for treatment of cancer with R201C-mutated GNAS.

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.

New drugs that target metabolic pathways have shown promise for the treatment of cancer, but the benefits of these drugs have been restricted to rare patients whose cancers have mutations in specific metabolic enzymes. Dr. Intlekofer identified a metabolic pathway whereby subpopulations of genetically identical cancer cells produce a metabolite called L-2-hydroxyglutarate (L-2HG) that induces stem cell-like properties associated with resistance to anti-cancer therapies. He is investigating the mechanisms by which L-2HG regulates the identity and function of cancer stem cells in order to determine whether targeting the L-2HG pathway represents a broadly applicable strategy for treating 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.