Damon Runyon News

Dr. Stevens aims to discover how engineered immune cells may be applied to the treatment of solid tumors that limit the infiltration of endogenous T cells. Dr. Stevens is using protein engineering to design synthetic receptors that direct T cells to tumor-associated antigens and facilitate penetration into the tumor. Once inside the tumor, the engineered cells should serve as signaling hubs to recruit additional immune cells and kill the cancer cells. 

Dr. Gao [HHMI Fellow] aims to understand the mechanism that proteins inside the cell use to enter peroxisomes. Peroxisomes are organelles that play important roles in fatty acid degradation, ether-phospholipid biosynthesis, and breakdown of hydrogen peroxide. Mutations in genes that cause faulty peroxisome function, particularly those that affect matrix protein import, result in a variety of severe inherited human diseases referred to as peroxisome biogenesis disorders (PBD).

Dr. Pae [Berger Foundation Fellow] is investigating the regulation of immune B cell proliferation in Germinal Centers (GCs). While this process is critical for bodies to resist infection, it must be carefully regulated. On one hand, not having enough B cells can lead to immunodeficiency and susceptibility to infections. Conversely, inappropriate activation is a major driver of malignant transformation and cancers such as B cell lymphomas. Dr. Pae’s research has the potential to shed light on how lymphomas form and to aid in the rational design of cancer therapeutics.

Dr. Silas is investigating how naturally occurring microbial and viral proteins might be utilized in the fight against cancer. Complex interactions in bacterial communities (such as the gut microbiome) can often lead to genetic information being exchanged, modified, and reused by competing species. Dr. Silas will develop strategies to control the composition and behavior of these communities, potentially helping to mitigate the threat from antibiotic resistance and infectious disease, which can result in serious clinical complications in patients.

Dr. Sheu-Gruttadauria is investigating the assembly and function of an important but poorly understood class of cellular compartments called membrane-less organelles. Classically, cellular activities are efficiently organized in membrane-bound compartments. Membrane-less organelles utilize newly discovered mechanisms for molecular organization that allow them to function in the absence of a membrane. Disruption of membrane-less organelles is a hallmark of many cancers, but how they are structured and regulated is a mystery.

Dr. Bakalar is developing new methods to discover the millions of interactions between T-cell receptors and foreign antigens that trigger an immune response. In many cancers, such as metastatic melanoma, immunotherapy depends on the ability of T cells to recognize and respond to tumor-specific neoantigens-new proteins found on cancer cells, which let the immune system know that these are not normal cells.

Non-small cell lung cancers are frequently driven by specific genetic alterations that can be targeted by precision medicine therapies. However, these therapies often result in partial responses, allowing some cancer cells to survive and become fully resistant to therapy. This ultimately limits patients' long-term survival. Dr. Blakely focuses on a particular type of lung cancer that is driven by mutations in the EGFR gene. This type of lung cancer frequently develops in younger patients who are non-smokers.

Acute myeloid leukemia (AML) is one of the deadliest blood cancers. Mutations in the FLT3 gene are the most common mutations in AML and are associated with poor outcomes in both adult and pediatric patients. Despite the importance of FLT3 mutations in AML, we still do not understand how FLT3 is regulated or the functional impact of novel FLT3 mutations identified in recent large AML sequencing studies.

The discovery that the immune system can be used to treat cancers has revolutionized treatment and given new hope for long-term response and survival to patients with lung cancer. Research has demonstrated that there are some predictors of response to immunotherapy, such as tumor mutation burden, which is increased in patients most likely to benefit from immunotherapy. Dr. Hellmann will focus on gaining a deeper understanding of how responses are initiated, how they remain durable, and what features characterize resistance when it occurs.

Squamous cell carcinoma (SCC) can occur on a number of epithelial surface tissues ranging from the skin and lung to the esophagus and oropharynx, and collectively, are the most common form of cancer in the world. Recent sequencing studies have found that mutations in epigenetic regulators that control gene expression frequently occur in all forms of SCC. Dr. Capell aims to harness the great accessibility of human skin to understand how altered epigenetics promotes cutaneous SCC.