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. 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.

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. Johnson is studying how genome rearrangements occur in cancer, using artificial pancreatic cancer organoids—clusters of cells that act as a model system. Cancer cells have unstable genomes that mutate and rearrange at a high rate compared to normal cells. Ultimately, Dr. Johnson hopes to understand how genome instability may be exploited to improve cancer treatments, including immunotherapy.

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. 

Dr. Kenney studies how microbes make natural products, a major source of new chemotherapy drug candidates. Dr. Kenney is identifying the chemical reactions used by microbes in nature to synthesize compounds that have the potential to act as chemotherapeutic drugs. Once the biological synthesis of these compounds is understood, this information can be used to identify, investigate, and ultimately re-engineer new families of natural products that can be evaluated for their potential as novel drugs.

Dr. LaBar is using budding yeast and computational modeling to study the basic processes that determine how cancer cell populations evolve in response their environment. Dr. LaBar aims to understand how the number of cells in a tumor may drive the evolution of cancer cells based on their supply of new mutations. His research has the potential to shed light on specific mutations that appear in certain cancers, alterations that allow cancer cell populations to grow abnormally, and strategies that will help predict the evolution of cancer cell populations and patient prognosis.

Dr. Lahvic is investigating how neighboring normal cells will try to impede the growth of cancer cells, and how a tumor escapes these controls. Dr. Lahvic aims to understand the genetic predispositions to cancer and find clues to a new way of preventing and treating cancer: activation of normal cells to directly fight a nearby tumor. While this work could hold relevance for all carcinomas, she is focusing on Ras mutations, which are especially common in pancreatic and colon cancers.

Dr. Lapointe examines how the synthesis of proteins (translation) is controlled, as dysregulated translation is a ubiquitous feature of cancer. He is focused on a key challenge: how regulation that originates at the “tail” end of a messenger RNA (mRNA, a genetic molecule that encodes a protein) impacts the start of translation, which occurs near the beginning of the mRNA. His goal is to reveal and analyze dynamic pathways that underlie this fundamental mechanism to control gene expression. Using an integrated approach of single-molecule fluorescence microscopy, structural, and biochemical strategies, this research should yield important insights into how translation is precisely regulated and how it is disrupted in a wide array of cancers. 

Dr. Levin is studying the interaction of host cells with the pathogens that infect them. These interactions cause repeated cycles of evolution, leaving “signatures” in both host and pathogen genomes specifically at molecular interfaces of host-pathogen binding. Evolutionary signatures can be used to pinpoint genes critical to disease progression. She is specifically examining the interactions between the pathogenic bacteria Legionella pneumophila and its and amoeba hosts. Her research will inform ongoing efforts to control this pathogen and reduce outbreaks. In addition, her studies have the potential to help cancer patients, who are immunocompromised after undergoing chemotherapy; they are susceptible to Legionella pneumophila infections that can result in a life-threatening, pneumonia-like disease associated with significant morbidity and mortality.