The RAS oncogene is mutated in 20% of all human cancers. Different types of mutations occur that promote cancer initiation and progression, yet we do not yet understand the specificity of how each mutation affects RAS’ ability to promote cancer. Unfortunately, despite decades of scientific effort, there are no effective therapies to directly target RAS mutant cancers. Dr. Burd proposes novel, mutation-specific studies of RAS in a variety of tumor types, starting with melanoma, thyroid cancer, and acute myeloid leukemia (AML). The reason why each cancer type appears to prefer one RAS mutant over another is unknown; however, she postulates that the subtle differences between mutants are critical for tumor formation.  Her research will lead to new understanding of RAS mechanism and function, resulting in better design of novel therapeutics to target RAS for treatment of cancer.

Dr. Chudnovskiy studies “antigen presentation,” an immune process by which dendritic cells capture antigens at the tumor site, migrate to the tumor-draining lymph nodes, and present tumor antigens to the effector CD4 and CD8 T cells that are responsible for anti-tumor responses. This is the first crucial step in successful cancer immunotherapy.

Dr. Dong studies how injury and pathogen invasion trigger a chain of inflammatory and repair responses that restore the damaged tissue. Defects in wound repair result in painful, non-healing ulcers that frequently affect aged individuals and diabetes patients. Malignant tumors are particularly severe complications, which often occur at sites of repetitive irritation and chronic wounds. She is investigating the roles of anti-microbial peptides during inflammation and wound healing, and hopes that these studies will provide insights about the cause and prevention of various carcinomas.

Dr. Insco studies advanced melanoma. Melanoma initiation and drug resistance rely heavily on factors that control gene expression. Proteins called Cyclin Dependent Kinases (CDKs) show promise as drug targets in multiple difficult-to-treat cancers and are enabling a method to “drug” the previously “undruggable” process of gene expression. She aims to determine whether any of the transcriptional CDKs could be an effective drug target in advanced melanoma. 

Dr. Kulalert focuses on how the skin is influenced by microbes. The skin is enriched with immune cells and highly innervated; nevertheless, the roles of neuroimmune crosstalk in cancer development and treatment remain largely unexplored. Sensory perception, especially pain sensation, is associated with cancer-related complications as well as chemotherapy. Because the microbiota plays a critical role in maintaining tissue homeostasis in the skin, he will explore whether sensory processing can also be modulated by the host-microbe interactions, particularly in the context of tumorigenesis and cancer treatment. These insights may provide novel tools to alleviate tumor progression and complications linked with cancer and chemotherapy, including pain sensation. 

Therapies that directly target cancer-promoting oncoproteins have revolutionized the treatment of cancer. Cancers, however, are primed to adapt and evolve in the presence of treatment, resulting in an ability to resume growth despite the presence of therapy. Utilizing cutting-edge new techniques that allow the determination of genetic alterations in single cancer cells, Piro aims to understand the principles that govern the evolution of resistance during therapy and identify novel therapeutic interventions that halt this process. His specific focus will be on resistance of lung cancer and melanoma to BRAF-targeted therapies. 

Dr. Naik is studying the interactions between immune cells and adult skin tissue stem cells in an effort to understand the how this crosstalk drives epithelial disorders, including chronic inflammation and cancer. Because adult tissue stem cells are long-lived cells that continually replenish tissues throughout an organism's lifetime, they represent ideal points of therapeutic intervention. Identification of inflammation-induced molecular changes in skin stem cells that drive epithelial dysfunction will facilitate the development of therapies for various epithelial inflammatory diseases and cancer.

Dr. Naik focuses on the fundamentally important interactions between the immune system, microbes, and adult skin tissue stem cells, and the consequences of such interactions for health and disease.  She studies how stem cells in epithelial tissues such as the skin sense and cope with inflammatory stress.  Her goal is to understand how inflammatory signals (either host-generated or microbial) provide adult stem cells with rapid, sensitive, and context-specific information, and how this process can go awry, potentially predisposing stem cells to diseases such as cancer. She hopes that her findings will facilitate the development of novel therapies.

Dr. Woo [HHMI Fellow] is using protein structures to illustrate the mechanisms of cancer-related processes. His research aims to overcome limitations of current techniques by using recent breakthroughs in “programmable DNA self-assembly” to develop protein framework structures that contain “pockets” with tunable size and shape for structural studies. If successful, his efforts will provide a general tool for structural biology and in turn benefit the mechanistic studies and therapeutic development for cancer.

Dr. Xi is studying signaling events that drive squamous cell carcinomas (SCCs), a common form of skin cancer. She focuses on WNT signaling, which is an important player in cell fate determination. It appears that WNT signaling is essential for SCC tumor formation, but exactly where and how it is required remains unknown. She is dissecting the activity of WNT signaling during the progression from normal epithelial cells to benign papillomas, and then to malignant SCC tumors. She is also investigating the critical downstream effectors of WNT signaling in this process, in order to identify improved targets for cancer therapeutics.