Dr. Murley is studying how the rapid growth of cancer cells exerts damaging stress on their subcellular compartments. In many cells, chronic stress of one of these compartments, called the endoplasmic reticulum, leads to cell death, but many types of cancer cells are able to avoid this fate. Recent findings point to the existence of secreted molecules released by cells when they are subjected to this stress. These molecules, whose identities are still unknown, can activate processes in neighboring cells, or in the secreting cells themselves, which protect them from this chronic stress. His goal is to identify these molecules and explore their role in cancer cell survival and other normal bodily functions. 

Dr. Nachtergaele is investigating the roles of RNA methylation, a process that chemically tags mRNA to alter gene expression and protein production. She has discovered a novel enzyme (m1A) that modifies RNA in this way and aims to uncover how malfunctions in this process can lead to cancer. Her investigations will expand the understanding of how mRNA modifications are regulated and result in altered cell signaling and growth in normal and cancer cells.  Building on this knowledge, her goal is to identify novel therapeutic targets for cancer.

Dr. Neggers is focusing on validating a new drug target for pancreatic cancer. Using large-scale genetic screening, Dr. Neggers discovered that a subset of cancers, including over 50% of pancreatic cancers, selectively require the VPS4A gene to proliferate and grow. When VPS4A is turned off, the cells stop dividing and die. He will study this vulnerability in clinically relevant patient-derived and mouse models of pancreatic cancer to understand how it functions. His research may help confirm whether this gene should be pursued as a significant drug target.

Dr. Nguyen is focusing on the key molecular pathways involved in T-cell unresponsive states, which prevents a full immune response against cancer. Within the suppressive cancer environment, T cells stop recognizing and fighting cancer cells. Dr. Nguyen is examining new genes and pathways that activate T cells and overcome the defects of unresponsive T cells. The insights gained from these studies may inspire new therapeutic strategies for cancer immunotherapy.

Dr. Norman aims to build a computational model of cancer genetics and understand the roles played by the complex interaction of genes. Though some cancers are characterized by very specific mutations, other cancers display a host of relatively common mutations, along with a string of infrequent mutations. He has developed technology to collect and integrate large data sets of experimental results with patient data to create a predictive model. This can be used to understand how a patient’s unique spectrum of mutations combine to give rise to cancer. In addition, his work may help to prioritize therapies in precision oncology and uncover hidden gene targets leading to new therapies.

Dr. Ong is investigating the molecular basis of paraneoplastic syndromes, which occur when a cancer causes unusual symptoms due to hormones produced by the tumor or antibodies produced by the immune system. They can affect the function of various distant tissues and organs in cancer patients, with deadly consequences. Dr. Ong is utilizing a new genetic tumor model in Drosophila that simulates many human paraneoplastic disorders: cachexia, immune dysfunction and early lethality. She aims to uncover how tumor cells impose physiological changes in host tissues at a distance with the hope of uncovering footholds for novel treatments.

Cancer survivors are at a higher risk of developing blood cancers than the general population due to the toxic effects of the treatments used to fight their cancer. Therapy-related blood cancers are often resistant to existing drugs and therefore extremely challenging to treat. Contrary to previous thought, recent studies show that the mutations causing these blood cancers can be identified in patients' blood many years before they received therapy. Dr. Papaemmanuil has discovered that the existing mutations alone are not sufficient to cause therapy-related cancer but require the acquisition of additional mutations that affect large segments of the DNA or "allelic imbalances." She will pursue further studies to screen patients and understand the mechanisms of therapy-related blood cancers. These findings will inform clinical strategies of early detection and targeted intervention to better treat this aggressive disease.

Dr. Peck is developing a new method to determine the three-dimensional structures of proteins. Though X-ray crystallography has determined protein structure for decades, many proteins involved in cancer form crystals that are a million-fold too small to be studied by this method. Applying the microscopy technique of electron cryotomography to these nanocrystals holds the potential to overcome this limitation and resolve the atomic architectures of these difficult-to-characterize proteins. Such detailed structural information is critical for understanding the molecular basis of cancer and accelerating drug discovery.

Dr. Reimer studies the molecular mechanisms that regulate the SWI/SNF family of chromatin remodelers, which is mutated in over 20% of cancers. Condensed DNA is stored within the nucleus as chromatin, which cannot be accessed for transcription to proteins. Chromatin remodelers are complex protein machines that alter DNA accessibility. Gain-of-function mutations lead to functional complexes with abnormal activities and are potential therapeutic targets. Dr. Reimer will use cryo-electron microscopy to understand how oncogenic mutations may disrupt the normal regulation and behavior of SWI/SNF remodelers.

Dr. Russell is investigating the mechanisms by which immune cells recognize influenza infection. Yearly influenza epidemics threaten immunocompromised individuals, including cancer patients, who are at an increased risk of complications following infection. His research combines virology, single-cell transcriptomic approaches, and computational biology to study innate immunity to viruses. Specifically, he aims to address the question of why immune responses to different influenza pandemics have differed so much-exploring why some strains are more or less immunogenic. He will expand his work by suggesting viral variants to create more effective vaccines that can bolster the immune response and better protect patients. These findings might suggest other therapeutic avenues, including the possibility of using such viruses in oncolytic anti-cancer therapy.