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Dr. Kang aims to identify mechanisms that eliminate unneeded cells in the brain. During animal development, extra neurons and neuronal connections are produced, but these unneeded neurons are selectively “eaten” by glia (another type of cell in the brain) in a process called phagocytosis.
Dr. Janetzko studies G protein-coupled receptors (GPCRs), a class of membrane-embedded proteins that relay signals about hormone and neurotransmitter binding to the inside of the cell. Several types of cancer cells hijack these proteins by keeping them in an active state (constitutively turned “on”) in order to promote their growth and allow them to metastasize. The activated GPCR often becomes a target for another set of proteins, called GRKs (GPCR kinases).
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. Qu is using Small Cell Lung Cancer (SCLC), a highly metastatic and lethal subtype of lung cancer, as a model to gain a better understanding of brain metastasis. Brain metastases are the most common type of intracranial tumors; they cause morbidity and mortality in a large number of cancer patients worldwide. The lack of preclinical models for brain metastasis has hampered our ability to better understand how primary tumors spread to the brain and grow there.
Dr. Termini aims to improve the success of hematopoietic stem cell transplants, which are used in the curative treatment of the majority of patients with leukemia or lymphoma. Prior to transplant, patients must undergo radiation therapy to decrease the number of cancerous blood cells. In order for hematopoietic stem cells to effectively repopulate the blood and immune systems of the transplant recipient, the stem cells must reach the bone marrow where they can expand.
Dr. Liu is using an in vivo experimental system to study how organs communicate with one another, specifically how the brain is influenced by factors produced in distant tissues. Our brains are protected from toxins and other harmful substances in the rest of our bodies by the blood-brain-barrier. Although the brain is isolated, there is significant clinical evidence demonstrating that changes in the body can significantly alter brain function.
Dr. Zhang aims to understand how the sensory organ called Area Postrema (AP) detects and generates nausea. Intense and protracted nausea and vomiting are major side effects of cancer therapy, with current anti-emetic drugs demonstrating only limited efficacy. She will use molecular and genetic approaches to disentangle the cellular diversity of the AP organ while identifying potential molecular detectors for nausea stimuli.
Dr. Sefik [HHMI Fellow] is examining the connection between obesity, cancer and the microbiome. An estimated 600 million people worldwide suffer from obesity, with 15-20% of deaths from cancer in the US alone linked to obesity. Recent studies in mice highlight the importance of intestinal bacteria and immune cells in obesity and colorectal cancer; however, these roles are not yet well characterized in humans.
Humans live in symbiosis with trillions of microbes, and there is growing evidence that these organisms can impact the development and progression of cancer.
Understanding molecular function in biological settings is essential for successful development of targeted therapies for cancer. Advances in biochemical profiling techniques have generated lists of molecules involved in cancer development and progression, but the mechanisms by which these molecules work together within cells and tumors remain largely unclear. Molecularly targeted cancer therapeutics based on incomplete understanding of the tumorigenic mechanisms often demonstrate initial response followed by cancer resistance.