Cancer cells form complex interactions with the various normal cells in their environment, including immune cells, fibroblasts, and blood vessels. These interactions are essential for cancer cells to grow, evade immune surveillance, and become metastatic or resistant to certain therapies.  Spatial transcriptomics refers to a method of visualizing the distribution of RNA molecules in a tissue sample, allowing us to assign specific cell types to their locations. Dr. Chu [William Raveis Charitable Fund Quantitative Biology Fellow] aims to develop a statistical framework to infer how different cell types interact with each other based on spatial transcriptomics data. He will use this statistical framework to study cell-cell interactions in both colorectal cancer and inflammatory bowel disease, a risk factor for colorectal cancer.

Dr. Chu will develop a hierarchical Bayesian statistical model to deconvolve the spatial transcriptomic data and then resolve cell type-specific information. Based on the deconvolved spatial data, he will then deploy a Bayesian spatial model to infer the interaction between various cell types.

Dr. Chung is developing a new engineering approach to create intelligent and tenacious T cells with durable anti-tumor activity. Her aim is to create enhanced T cells that will infiltrate tumors, kill cancer cells, and persist long-term to prevent recurrence. Dr. Chung will use cutting-edge, multi-disciplinary approaches, including bioinformatics, protein and genetic engineering, and tumor immunology, to design a synthetic T cell differentiation pathway. This T cell reprogramming platform has the potential to transform cellular immunotherapies (such as CAR T) into "smarter" cells that target cancer with persistence and enhanced potency.

Dr. Cissé [Merck Fellow] aims to define the functional importance of nutrient sensing within the tumor microenvironment. How cells sense and adapt to the availability of nutrients in their environment is incompletely understood, but one key pathway is the signaling system anchored by the mTORC1 kinase. The mTORC1 kinase regulates cell growth and metabolism in response to nutrients such as amino acids and glucose. Aberrant mTORC1 signaling is implicated in several cancers, including melanoma, known to be heavily influenced by factors in the microenvironment such as nutrient availability. Dr. Cissé aims to understand how tumor metabolism senses and responds to varying nutrient levels, which will be essential for developing novel therapeutic targets.

Dr. Cote is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr. Cote is combining tissue-specific genetic manipulations and laser cell ablations with live imaging during Caenorhabditis elegans digestive tract development to reveal how intracellular organization in one cell type can influence the alignment, polarity, and function of cells in the neighboring tissues.

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 [HHMI Fellow] 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.

Myelodysplasia and acute myeloid leukemia are blood cancers with a poor prognosis. At the root of these malignancies are cells harboring mutant forms of proteins with dysfunctional activity which results in abnormal cell behavior and drives disease progression. The focus of my project is the development of new therapeutics that precisely identify cells with mutant forms of the proteins and, by harnessing their aberrant biological activity, causes those cells to self-destruct. These selective therapeutics will be able to kill cancer cells but leave the healthy cells intact proving more effective and having less side-effects than the chemotherapies currently in use.

Dr. Culp [The Mark Foundation for Cancer Research Fellow] is exploring how the chemical components of food interact with the gut microbiome and how these interactions impact cancer risk. While diet is an important factor in cancer prevention, it is unclear how specific food components affect cancer risk in an individual. A key piece of information not currently understood is how dietary compounds are metabolized by the gut microbiome, and how these transformations alter the biological activity of the compound on the host. Dr. Culp is mapping the transformation of dietary compounds by bacterial members of the gut microbiome, deciphering the associated mechanisms, and testing their cancer-associated effects in mouse models. Together, these studies will provide a basis to inform intervention strategies addressing the link between the microbiome, diet, and cancer risk.

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 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 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.

Dr. Gao [The Mark Foundation for Cancer Research Fellow] studies how the tumor microenvironment influences anti-tumor immune responses. Her research focuses on lipid metabolism in cytotoxic T lymphocytes (CTLs), a specialized population of white blood cells that kill malignant cells. To defend against this attack, tumors release lipid metabolites that can incapacitate infiltrating CTLs. Consequently, these metabolites create an immunosuppressive environment and promote tumor progression. Dr. Gao aims to unravel the pathways utilized by these harmful lipids. She is also investigating whether modifying lipid metabolism in immune cells can unleash CTL response and accelerate tumor shrinking. These studies have the potential to identify new therapeutic targets that will improve immunotherapy.