Dr. Chen is genetically re-engineering cancer-infecting viruses so that, once inside a tumor cell, they flip on a built-in “self-destruct” circuit called pyroptosis. This explosive form of cell death not only wipes out the infected cell but also broadcasts an alarm that rallies the immune system against the whole tumor. By pairing this viral upgrade with an ultrasound trigger, Dr. Chen aims to turn treatment-resistant pancreatic cancer—and, ultimately, other solid tumors—into diseases the immune system can eradicate. Dr. Chen received his PhD and MS from Zhejiang University, Hangzhou, and his BS from Southwest Jiaotong University, Chengdu.

For gene activation, transcription factors (TFs) must bind to enhancers, often with multiple TFs binding at the same site, and recruit other proteins known as cofactors and polymerases. The interactions between TFs and cofactors are usually nonspecific, meaning the cofactors are interchangeable, which limits our understanding of precise gene activation. Dr. Chen will design new proteins that bind the cofactors with high specificity to clarify the contribution of each cofactor. This research will not only provide new insights into the mechanism of gene regulation but also provide new platforms to modulate gene expression with high precision. Dr. Chen received his PhD from the University of Washington, Seattle, his MS from Cornell University, Ithaca and his BS from Shandong University, Jinan.

Fatigue is the most common symptom experienced by patients with cancer or undergoing cancer treatment. While chronic inflammation and hormonal imbalance have been suggested as possible causes, the roots of cancer-related fatigue remain unclear and thus we lack effective treatments. Dr. Chiu [HHMI Fellow] seeks to illuminate the physiological basis of fatigue using interdisciplinary approaches that combine the strengths of neuroscience, immunology, and computational biology. Through the lens of brain-body interactions, Dr. Chiu aims to identify key molecular and cellular components of fatigue with the goal of improving treatments for cancer and other severe diseases, such as long COVID. Dr. Chiu received her PhD from the California Institute of Technology, Pasadena and her MS and BS from the National Taiwan University, Taiwan.

Dr. Choi develops a technology called “Molecular recording”, which allows the recording of cellular events and their lineage information into each cell’s genome. These innovative tools are critical for understanding the development of individual cells, both in normal developmental processes and in diseases like cancer. Recently, Dr. Choi has successfully demonstrated this technology by engineering human cancer cells to record their lineage or signaling events in a culture dish (“in vitro”) using CRISPR-based genome editing methods. Moving forward, Dr. Choi plans to further develop these methods to study cancer development. The goal is to uncover how specific characteristics of cancer cells emerge, ultimately identifying new targets for treatment.

Macrophages are specialized immune cells responsible for “eating” harmful cells, presenting antigens to T cells, and initiating inflammation by releasing signaling molecules called cytokines. Macrophages could potentially be activated to attack tumor cells, but for reasons that are currently unclear, they instead signal for the tumor to grow faster and become more invasive. Dr. Courvan is investigating how macrophages respond to the low-oxygen environment inside tumors, and specifically how they regulate gene expression through post-transcriptional mechanisms in low-oxygen conditions. With this research, he hopes to uncover new ways to leverage the body's immune system against cancerous cells. Dr. Courvan received his PhD from Yale University and his BS from the University of Connecticut.

Dr. Cuevas-Navarro’s [Berger Foundation Fellow] research project focuses on targeting mutations in the RAS genes (HRAS, NRAS, and KRAS), present in about 30% of cancer patients and notorious for driving aggressive tumor growth. Dr. Cuevas-Navarro aims to mitigate these mutations’ effects by using pharmacological agents to enhance a biochemical process that regulates RAS proteins. His project will investigate the mechanism of action of these compounds and assess their effectiveness in patient-derived cancer models. This research has the potential to expand treatment options across various cancer types, including those where current treatments are limited. Dr. Cuevas-Navarro received his PhD from University of California, San Francisco and his BS from University of California, Davis.

T cell therapies have led to promising results in treating blood cancers, but new approaches are required to translate these results to solid tumors. In solid tumors, T cells face unique challenges in the tumor microenvironment (TME), which limits the persistence and efficacy of adoptive T cell therapies. In T cell lymphomas (TCLs), tumor cells overcome many of the same challenges through acquired mutations. Fueled by natural selection, tumor mutations produce novel and elegant solutions to address T cell deficits in the TME. Understanding that these modifications may be superior to current bioengineering capabilities, Dr. Devany [Bakewell Foundation Fellow] plans to introduce gain-of-function mutations into therapeutic T cells to grant them the ability to survive, proliferate, and function in the TME. He will determine how each mutation restores different aspects of T cell function, allowing for the design of combinations of mutations that act synergistically. His results will aid in the development of next-generation T cell therapies to cure solid tumors. Dr. Devany received his PhD from University of Chicago, Chicago and his BS from University of California, Santa Barbara.

In many cancer types, microbiota have emerged as influential components of the tumor environment. Dr. Dohlman [Meghan E. Raveis Fellow] studies cancer associated bacteria, fungi, and viruses to understand how microbial species colonize different tumors and their role in disease progression. The factors that drive microbial colonization of tumor tissues remain poorly understood, but uncovering these mechanisms could lead to new strategies for cancer diagnosis and treatment. To this end, Dr. Dohlman is developing computational tools for detecting microbiota in tumor tissues and studying the genomes of tumor-associated microbiota for clues about their potential role in cancer. In parallel, he is analyzing tumor genomic data to understand host features that in turn influence microbial colonization. Dr. Dohlman received his PhD from Duke University, Durham and his BA from Wesleyan University, Middletown.

Global increases in metabolic syndrome, obesity, and diabetes are likely related to the overconsumption of hyper-palatable, cheap, ultra-processed food containing high amounts of added sugar and fat. Intriguingly, the vagus nerve has been discovered as the key conduit relaying information about sugar or fat ingestion from the gut to the brain, where a preference for sugar or fat is then developed and reinforced. Dr. Du [HHMI Fellow] aims to understand how the neurons are organized in the gut-brain vagal axis to sense sugar and fat, and to identify and characterize the neural circuits downstream of the gut-brain vagal axis that produce an insatiable appetite for sugar and fat. Understanding the basic biology of the gut-brain axis can provide important insights and strategies to help combat overconsumption of highly processed foods rich in sugar and fat, which may contribute to lowering the risk of metabolic diseases and cancer. Dr. Du received his PhD from The University of Texas Southwestern Medical Center, Dallas and his BS from the Tsinghua University, Beijing.

Courtney Ellison, PhD [Marilyn and Scott Urdang Breakthrough Scientist] is investigating how single bacterial cells join together to form complex, multicellular structures called biofilms. Biofilms protect bacterial cells from antibiotics and antimicrobial agents, making them difficult to eliminate. Some biofilm-forming species may cause certain cancers, and biofilms of infectious bacteria threaten immunocompromised patients such as those undergoing chemotherapy. Dr. Ellison focuses on bacterial appendages called type IV pili that play a crucial role in biofilm formation. Understanding the role of pili and their contribution to biofilm progression may lead to novel therapies to eliminate biofilms.