2017–2018

Preclinical cancer target validation: how not to be wrong

A Howard Hughes Medical Investigator since 1998, Dr. Kaelin's research seeks to understand how, mechanistically, mutations affecting tumor-suppressor genes cause cancer. His long-term goal is to lay the foundation for new anticancer therapies based on the biochemical functions of tumor suppressor proteins. His work on the VHL protein helped to motivate the eventual successful clinical testing of VEGF inhibitors for the treatment of kidney cancer. Moreover, this line of investigation led to new insights into how cells sense and respond to changes in oxygen, and thus has implications for diseases beyond cancer, such as anemia, myocardial infarction and stroke.

The molecular logic of synapse formation in the brain

Thomas Südhof is interested in how synapses form and function in the developing and adult brain. His work focuses on the role of synaptic cell-adhesion molecules in establishing synapses and shaping their properties, on pre- and postsynaptic mechanisms of membrane traffic, and on impairments in synapse formation and synaptic function in neuropsychiatric and neurodegenerative disorders.

Sugar and the beating heart - the conundrum of heart failure in diabetes

Dr. Abel's current research interests focus on elucidating the molecular mechanisms leading to cardiac dysfunction in diabetes and the regulation of myocardial growth and metabolism by insulin signaling.

Inflammation and hematopoietic stem cell regulation

Dr. Passagué's research investigates the biology of blood-forming hematopoietic stem cells in normal and deregulated contexts such as development of hematological malignancies and physiological aging.

Race, risk, and resilience: understanding racial differences in cognitive aging and brain pathology

Dr. Barnes' research focus is on racial disparities in chronic diseases of aging, with a particular focus on Alzheimer’s disease and cognitive decline. 

Mitochondria control of physiology and disease: beyond ATP

For decades, the mitochondria have been primarily viewed as biosynthetic and bioenergetic organelles generating metabolites for the production of macromolecules and ATP, respectively. Our work has elucidated that mitochondria have a third distinct role whereby they release reactive oxygen species (ROS) and metabolites such as L-2-hydroxyglutarate to initiate physiological and pathological processes including hypoxic activation of HIFs, cellular differentiation, T cell activation and cancer cell proliferation. Thus, mitochondria function as signaling organelles.

Gut reactions: host microbiome interactions in the intestine in health and disease

The gastrointestinal tract is home to a large number and vast array of bacteria that play an important role in nutrition, immune-system development, and host defense. In inflammatory bowel disease there is a breakdown in this mutualistic relationship resulting in aberrant inflammatory responses to intestinal bacteria. Studies in model systems indicate that intestinal homeostasis is an active process involving a delicate balance between effector and immune suppressive pathways. For her presentation, Dr.

Of bones, brain, and fat: macrophages and the control of homeostasis

Over the past ten years, we have investigated the developmental origin and homeostasis of macrophages and the related cell types monocytes and dendritic cells. These cells play a major role in development, homeostasis and diverse types of cancer and can either restrain or promote cancer progression and metastasis. The Geissmann lab is now building on previous work to investigate mechanisms by which tissue macrophages may control tissue growth and metabolism and whether these same mechanisms play a role in cancer initiation and development.

The cryo-EM revolution

Research in the Subramaniam lab over the last decade has been guided by the vision that emerging tools in 3D electron microscopy hold great promise for imaging cells, viruses and protein complexes at high resolution in their native states, thus bridging a major gap in structural biology. In his talk, he will review examples of recent progress ranging from determination of protein structures at atomic resolution to imaging viruses, cells and tissue at nanometer resolution.

Mechanistic basis of cancer immunotherapy

Dr. Mellman's laboratory is known for advances in fundamental cell biology, particularly in the area of membrane traffic (including the discovery of endosomes), and applying these insights to understand the cellular basis of the immune response. His laboratory's pioneering contributions to cancer immunotherapy include elucidating how dendritic cells initiate immunity or maintain immune tolerance, forming the basis for efforts in cancer vaccines.