Dr. Waizman [Connie and Bob Lurie Fellow] is trying to understand how we can apply principles of resilience in the context of colorectal cancer. He is investigating how a cellular alarm signal known as Interleukin-25 triggers the immune system to create protective layers within barrier tissues, such as the intestine, to increase their environmental defenses and capacity for tissue regeneration after injury. These layers could serve two-fold functions–in prevention of colorectal cancer and the prevention or reduction of adverse side effects of cancer treatment, which serve as a barrier to continued treatment. Dr. Waizman received his PhD from Yale University, New Haven, and his BA from Cornell University, Ithaca.

Mitochondria are best known as the cell’s power plants, but they also help cells respond to stress and repair their own DNA. A mitochondrial protein called ATAD3A plays a key role in these processes and is found at abnormally high levels in many aggressive cancers such as glioblastoma, breast cancer, and colorectal cancer, where it contributes to tumor growth and resistance to treatment. Dr. Orta studies how ATAD3A acts as a sensor of mitochondrial DNA damage—detecting trouble inside the mitochondria and helping signal to other parts of the cell, like the endoplasmic reticulum, that stress responses are needed. Using cryo-electron microscopy along with biochemical and cell-based approaches, she aims to uncover how ATAD3A is regulated and how its function supports cancer cell survival. Ultimately, she hopes to expose new ways to target mitochondrial stress pathways in cancer. Dr. Orta received her PhD from California Institute of Technology, Pasadena, and her BS from the University of Texas at El Paso, El Paso.

There are two key types of cancerous mutations: one that turns on growth signals too strongly, like a car with a stuck accelerator, and the other that turns off safety mechanisms, like a car with broken brakes. While some cancers can be treated with drugs that block overactive growth signals—such as Gleevec for chronic myeloid leukemia—there are currently no effective treatments for cancers caused by the loss of these safety mechanisms, also known as tumor suppressor genes. Notably, mutations in TP53, one of the most common tumor suppressor genes, are abundant in almost all cancers, including breast, lung, and ovarian cancers. Dr. Zheng’s research focuses on reactivating these impaired tumor suppressor genes, such asTP53and FBXW7, to develop new treatment options for a wider range of cancers and to address resistance to existing therapies.

Emerging evidence underscores the profound impact of the gut microbiome, a collection of microorganisms within our digestive system, on cancer. These microorganisms collectively generate various metabolites that can significantly influence cancer progression and treatment outcomes. Dr. Zeng [Fraternal Order of Eagles Fellow] is employing synthetic communities and mouse cancer models to delve into the intricate connections between cancer and the microbiome. His synthetic communities, comprised of over 100 strains, allow for precise manipulation of the microbiome to elucidate the role of specific microbial metabolites in cancer. Additionally, Dr. Zeng is studying community-scale metabolism and using genetically edited strains to design synthetic communities with desired metabolic profiles. These approaches will gain valuable insights into microbiome-cancer interactions and establish a broadly applicable strategy to harness the therapeutic potential of gut microbiome. Dr. Zeng received his PhD from Princeton University, Princeton and his BS from Tsinghua University, Beijing.

Mitochondria harbor independent genetic material known as mitochondrial DNA (mtDNA). This compact, circular molecule encodes proteins essential for the assembly of the mitochondrial electron transport chain to generate energy in form of ATP. Like nuclear DNA, mtDNA is susceptible to damage and mutations. One of the most common disease-causing aberrations of mtDNA is termed “common deletion.” This aberration disrupts mitochondrial function, resulting in neuromuscular diseases and potentially certain cancers, including colorectal cancer. Due to a lack of tools to modify the mitochondrial genome, researchers currently do not understand the mechanisms behind common deletion. Dr. Kavlashvili [Timmerman Traverse Fellow] aims to investigate by using cutting-edge molecular biology tools to edit and visualize mtDNA genomes. She will then be poised to unravel impacts of this deletion on various tissues, in order to ultimately mitigate its pathological impact. Dr. Kavlashvili received her PhD from Vanderbilt University, Nashville and her BS from University of Iowa, Iowa City.

Most cancers develop in the epithelial tissue, which includes the skin and internal organ linings.  Hemidesmosomes (HDs) are adhesive structures that anchor epithelial cells to the underlying base layer and maintain tissue integrity. While HD disassembly occurs normally during wound healing, tumor cells can exploit this process to detach and spread to other parts of the body. Dr. Bagde [Bakewell Foundation Fellow] is studying how HD components interlock like Lego blocks to form stable HDs in healthy tissues and how they disassemble in cancerous tissues. To investigate this phenomenon, Dr. Bagde plans to develop organoids—self-organizing mini-organs grown in a petri dish to study disease progression. By creating simple base layers that simulate the supportive properties of the native organ base layer, he plans to promote the growth of both normal and cancerous organoids. This work has the potential to support the development of personalized cancer therapies based on patient-derived tumor samples. Dr. Bagde received his PhD from Cornell University, Ithaca and his MS and BS from the Indian Institute of Science Education and Research, Pune.

T lymphocytes, an important component of the immune system, recognize infected or cancerous cells with great specificity, ensuring targeted elimination. These potent cells are kept in check by regulatory T cells, the guardians of the immune system. While essential for curtailing excessive inflammation and preventing autoimmunity, their immunosuppressive properties can promote the development and progression of cancer. Regulatory T cells are distinguished by the presence of a protein called Foxp3, which plays a critical role in their differentiation, function and fitness. Foxp3 deficiency results in fatal autoimmune inflammatory disease, underscoring its importance for maintaining organismal health. Despite its significance, however, the reliance of regulatory T cells on Foxp3 in disease contexts like infection and cancer remains incompletely understood. Dr. Schiepers [HHMI Fellow] will study the fate and function of regulatory T cells in these settings using mouse genetics approaches and disease models of melanoma and colorectal cancer. Dr. Schiepers received his PhD from The Rockefeller University, New York and his MS and BS from Utrecht University, Utrecht.

The Western diet, characterized by low dietary fiber and high saturated fat content, is strongly correlated with incidence of CRC. This diet rapidly alters the composition and function of the gut microbiome, inducing microbial imbalance and inflammation, two major hallmarks of CRC. These changes are thought to be caused by diet-induced oxygenation of the gut environment. Most beneficial gut bacteria cannot survive this oxygenated environment, but harmful microbes can thrive in this setting and further exacerbate inflammatory responses. The response of bacteria to oxygen is varied and poorly understood. Dr. Reddy [Connie and Bob Lurie Fellow] aims to elucidate the mechanism underlying oxygen tolerance in bacteria and find interventions to restore normal oxygen levels.  The findings from this project will delineate the contributions of exercise and diet to establishing the oxidative environment of the gut and illuminate the mechanism allowing certain microbes to withstand redox stress. Dr. Reddy received her PhD from Harvard University, Cambridge and her BS from University of Connecticut, Mansfield.

Emerging evidence implicates the pathogenic bacterium C. difficile as an initiator of colorectal cancer. C. difficile exposure can lead to chronic recurrent disease that is difficult to clear with antibiotics. The generation of spores is a well-studied mechanism used by C. difficile to persist; however, other mechanisms of recurrent infection remain poorly understood. Dr. Price [Merck Fellow] hypothesizes that biofilms may function as reservoirs of C. difficile and aims to elucidate their role in disease relapse. She will employ innovative imaging strategies to visualize the composition and development of C. difficile biofilms in the gastrointestinal tract, with the goal of generating insight that will improve treatments for C. difficile infections and identify strategies to prevent colorectal cancer. Dr. Price received her PhD from University of Louisville, Louisville and her BS from University of Tennessee, Knoxville.

In many cancer types, microbiota have emerged as an influential component of the tumor environment. Dr. Dohlman [Meghan E. Raveis Fellow] studies 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.