Dr. Bar-Peled studies how cancer cells adapt to stress environments, focusing on oxidative stress.  His research focuses on understanding how cells sense and respond to specific changes in their environment by activating singling pathways that lead to uncontrolled growth.  He recently studied a particular pathway in non-small cell lung cancer and identified a “druggable” protein that could be targeted with small molecules and disrupt this uncontrolled growth. He plans to pursue this specific target and use the same strategy for identifying druggable pathways in other cancers that currently lack effective therapies.

Dr. Brooks is analyzing cancer genome sequence data to identify DNA mutations that affect RNA splicing, a form of gene processing and regulation. By characterizing these mutations, her work will provide further understanding of the role of splicing alterations in cancer as well as insight into the functional consequences of cancer mutations.

Dr. Chen aims to understand the relationship between small RNAs and cancer.  Small RNAs are important regulators of genetic networks inside the cell; perturbation of these networks can lead to malignant cell growth.  His goal is to develop anti-cancer drugs and therapies by targeting the process of small RNA production.

Dr. Leppek [Layton Family Fellow] aims to combine RNA and ribosome biology with developmental biology to investigate how cells regulate protein synthesis through a process called translation. This process requires regulatory mechanisms to fine-tune when and where genes are expressed. Defective expression of certain genes gives rise to uncontrolled growth and metastasis of cancer cells. She will identify and characterize molecular components that play a functional role in mediating translational control during embryogenesis. This will be invaluable for our understanding of how deregulation of accurate gene expression underlies human diseases such as cancer.

Dr. Liu [Layton Family Fellow] studies lung biology. The lung is innervated by diverse types of sensory neurons, collectively called pulmonary sensory neurons. These neurons detect a variety of physiological stimuli from the lung and inform the central nervous system about the state of the lung. Lung cancer, one of the most common cancers with a high rate of lethality, is associated with symptoms such as chronic cough, shortness of breath, and referred cranial facial pain. Her research will examine how pulmonary sensory neurons recognize and respond to lung tumors, and how this tumor sensing influences tumor biology. She aims to understand which populations of pulmonary sensory neurons mediate lung cancer-associated clinical symptoms, how these neurons alter their behaviors in response to tumor growth, and how activating pulmonary sensory pathways affects cancer progression and metastases.

Dr. Nachtergaele [HHMI Fellow] is investigating the roles of a chemical modification of mRNA called methylation. Many enzymes that add and remove RNA modifications impact developmental processes and cancer proliferation, but how they are regulated remains a mystery. She aims to identify the mechanisms by which mRNA methylation alters gene expression and eventually results in altered cell signaling and growth. Her goals are to understand these regulatory principles, to uncover how they become misregulated in disease, and to exploit these processes to identify novel cancer therapeutic targets.

Many cancers initially respond to therapy. However, cancers often acquire resistance and stop responding to further treatment. Small cell lung cancer (SCLC) is an example of a cancer that is highly sensitive to initial treatment, but quickly acquires a vicious resistance resulting in a five-year patient survival rate of less than 4%. In order to combat drug resistance and improve the quality of life for patients with SCLC, it is important to understand the key genetic changes and cellular pathways that drive resistance.

Dr. Oliver will use the most innovative next-generation sequencing technologies to comprehensively identify critical genetic changes associated with resistance. These findings will be essential for understanding how lung cancer, and potentially other types of cancer, evades chemotherapy. In addition, this work will identify novel pathways that could be targeted to re-establish drug sensitivity and thereby provide new treatment options for patients with drug-resistant disease.  

Dr. Van Nostrand aims to understand how signaling pathways involved in the energetic and metabolic stress responses prevent cancer. She will generate mouse models harboring specific mutations that prevent the stress response, and evaluate the effects of these mutations on lung cancer development. Furthermore, using exercise and caloric restriction, she will elicit the metabolic stress response in these animals to understand how energetic stresses prevent cancer development and progression. This work will both expand knowledge of how cells respond to energy stress and metabolic changes to suppress tumorigenesis and aid in establishing effective preventative and therapeutic strategies for cancer patients.

Dr. Wang seeks to understand the mechanisms by which tumor cells become resistant to drug therapy and spread to distant organs. She is utilizing functional genomics tools to identify novel pathways modulating these processes in the hope of developing new therapies to augment treatment response in cancer patients.