Dr. Miller is investigating how cells ensure the correct partitioning of genetic material during cell division. Errors in this process occur in nearly all tumor cells and are the leading cause of miscarriages and congenital birth defects in humans. The vast majority of solid tumors have incorrectly positioned chromosomes, causing high levels of genomic instability and DNA damage. Very little is known about how chromosome segregation becomes so defective during tumorigenesis. His research is focused on elucidating the mechanisms of both accurate and defective chromosome segregation with the goal of determining whether there are opportunities for development of new cancer therapeutics.

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. Ordovas-Montanes studies how inflammation in the gut influences individual epithelial and immune cells. Inflammation is one of the largest risk factors for developing colon cancer. A better understanding of the cellular factors involved in precipitating malignancy may lead to novel approaches for blocking the initiation of cancer and restoring the gut to a healthy balanced state.

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.