Tumor Initiation and Maintenance
The Tumor Initiation and Maintenance Program
seeks to identify the cells that give rise to tumors and the signals that allow these cells to expand uncontrollably. Several members of the program focus on Stem Cells and Development, studying the stem cells that generate the brain, the mammary glands, the muscles and the skin, and how mutations transform these cells into cancer cells. Another major theme is Cell Growth Signaling, which includes investigation of the growth factors that cause cells to proliferate, and the proteins within cells that allow them to respond to these factors. Finally, several researchers in the program study RNA Biology, analyzing the ribonucleic acid (RNA) molecules that play key roles in regulating cell division, differentiation and survival.
Cell Death and Survival Networks
The focus of the Cell Death and Survival Networks Program
is to study how cancer cells reprogram their metabolism and protein homeostasis to survive nutrient stress conditions associated to tumor progression and how they might use autophagy to prevent various forms of cell death, including apoptosis and necrosis. We address these fundamental biological questions at the organismal level, utilizing relevant models of human cancer, and at a cellular and detailed structural level. This interdisciplinary approach, together with our capability of drug discovery, positions our program at the leading edge of translating basic discoveries into better medicines.
Tumor Microenvironment and Metastasis
The Tumor Microenvironment and Metastasis Program
aims to understand the molecular basis of how cells interact with each other and with the molecules in their environment, and how these processes promote tumor growth and metastasis. We also explore how the immune system is altered to promote tumor growth, and how tumor cells stimulate the production of new blood vessels (angiogenesis) to gain access to nutrients and metastasize. This is the starting point for the identification of strategies to modify the tumor microenvironment to inhibit tumor growth and metastasis.
The Degenerative Diseases Program
is focused to understand how the cell discriminates functional from nonfunctional proteins to target the latter for degradation. The answers to these questions will lead to novel therapeutics for many diseases associated with aging. We study intrinsic cellular mechanisms that recognize misfolded/damaged proteins and target their degradation. Importantly, our findings have demonstrated the damaging impact of oxidative/nitrositative stress on protein structure and function in disease pathogenesis, for example the neurodegenerative diseases of Alzheimer’s and Parkinson’s, and their impact on neural synaptic structure and signaling. Finally, defective protein folding and/or degradation are now implicated in many diseases ranging from cancer to metabolic and inflammatory response syndromes.
Immunity and Pathogenesis
The Immunity and Pathogenesis Program
is broadly defined by the focus on cellular and molecular mechanisms of the host immune system, versus the mechanisms that viruses and other pathogens employ to evade immune recognition. Current efforts include approaches to characterize host microenvironments and signaling pathways impacted by viral pathogens; neuroinflammation; mucosal immunology and the microbiota; immune regulation by members of the TNF superfamily; functional discrimination of CD4+ T cell subsets and understanding the molecular determinants of B cell differentiation.
The Human Genetics Program
wants to understand how inherited conditions cause disease. Often these conditions have existed for thousands of years and families have struggled with how to manage their loved ones illness. Parents face family planning decisions and where to turn for answers to many questions. Technological breakthroughs in Human Genetics offer an unprecedented opportunity to provide solid information and guidance.
Development, Aging and Regeneration
The Development, Aging and Regeneration Program
aims to understand these processes in model organisms and ultimately in humans. We are interested in elucidating the secrets and delineating the mechanisms of how embryos and organs form, and how they deteriorate with age or disease, with the goal of identifying potential ways to reverse or ameliorate the debilitating insults of age or disease in humans.
Bioinformatics and Structural Biology
The Bioinformatics and Structural Biology Program
The Cardiovascular Pathobiology Program
emphasizes the study of heart failure, heart attack, hardening of the arteries, stroke, and poor circulation – in sum, the disease biology responsible for the number one cause of morbidity and mortality in our society.
The Metabolic Disease Program
is focused on metabolic diseases that primarily affect the metabolic syndrome, which refers to metabolic complications that influence development of cardiovascular disease, obesity and type II diabetes. Metabolic Syndrome develops when the body’s normal process of sensing dietary nutrients for utilization of energy and storage are fundamentally perturbed through genetic, epigenetic or environmental mechanisms.
Genomic Control of Metabolism
The focus of the Genomic Control of Metabolism Program
is to dissect and understand the genomic and epigenetic regulatory mechanisms responsible for proper metabolic control to maintain homeostasis. We primarily study diseases in adipose tissue, liver, muscle and immune cells. Particular emphasis is put on defining the role of key transcriptional regulatory proteins and nuclear hormone receptors in metabolic processes at the cellular level, in animal models, and in human disease. Another theme of our research is the systems level analysis of metabolic processes using integrated experimental and bioinformatics approaches.