Cancer cells hijack normal cellular and developmental programs. Scientists in the CDB home area investigate how genetic hits reprogram cancer cells and enable aggressive phenotypes. As in development, both cell autonomous regulation and the complex interplay of cell-cell interactions contribute to tumorigenesis. Accordingly, CDB cancer research overlaps with the other thematic areas of the home area. For example, how can signaling be disrupted to more specifically target cancer cells in therapeutic approaches? Which cancer sub-types fit the cancer stem cell hypothesis? What is the role of differentiation and de-differentiation in the plasticity and heterogeneity of cancer? How do epigenetic changes cooperate with the mutational genetic changes underlying cancer? How do the vascular and lymph systems contribute to tumor biology? How do multiple aspects of cancer, such as metabolism, signaling and epigenetics, interact at the systems level? The combined expertise of the basic science and medical labs, and the proximity of the main campus and medical campus at UCLA, facilitate the translation of research findings into clinical trials. Conversely, lab research and small animal cancer models are guided by the analysis of patient samples. Students have the opportunity to delve deeply into a research topic, and to bridge labs through multi-disciplinary studies.
Most cell fate decisions are made within the nucleus as a result of a dynamic regulation of chromatin structure and function. In CDB, various labs study Chromatin Biology in different model orgnanisms (Plant, Drosophila, Zebrafish, Mouse, Human) and employ novel and emerging techniques such as ChIP-Seq, DNA methylome analysis, Chromatin Capture (4-C, HiC). These groups probe basic questions in Cell and Developmental biology though an exploration of what makes Chromatin dynamic, and how chromatin states regulate transcriptional machinery to drive cell fate. CDB is home to faculty who explore basic questions in cell and developmental biology such as how does regulation of the DNA methylation regulate germ cell formation? How does chromatin change during reprogramming of cell fate by transcription factors? Does Chromatin remodeling drive development, or occur as a consequence? Through significant interaction with the Gene Regulation Home Area, this group has organized seminar series, journal clubs, and specialized curriculum designed to merge bioinformatics with basic cell biology to answer important questions in Chromatin Biology.
Regulated growth and cell type specification are critical early steps in animal development, but the formation of organs and organisms also requires dynamic rearrangements of cells and tissues, a process known as morphogenesis. During morphogenesis cells must remodel their membranes and cytoskeletons to change their shapes, migrate to appropriate locations, and communicate with one another to coordinate their movements. Scientists in the CDB Home Area are studying how these fascinating, dynamic processes are regulated to form diverse tissues and organs. For example, how do cells segregate into coherent germ layers during gastrulation? How do vascular cells form an interconnected tubular network of veins and arteries? How do diverse cells come together to create the complex architecture of organs such as the pancreas, intestine, heart, skeleton and skin? How do cells of the nervous system wire up into intricate and precise neural circuits? CDB researchers address these and many other morphogenetic questions using model organisms, such as flies, fish and mice, and cutting edge imaging and molecular techniques. Within the broader CDB community, labs frequently collaborate based on common interests in particular model organisms, organs, or subcellular structures. These interactions ensure that students interested enjoy both broad and specific interactions, enriching their training environment and tying them to an active community exploring the frontiers of developmental biology.
The study of plant biology encompasses important questions specific to plants as well as basic biological questions of growth and development. Plant biologists in the CDB home area use powerful model organisms such as Arabidopsis and Chlamydomonas, as well as important crop plants like soybean to address these questions. Taking advantage of the latest technologies in microscopy, next generation sequencing, and whole genome analyses, CDB plant biologists are uncovering molecular mechanisms related to how plants grow, how they respond to biotic and abiotic cues, how tissues and body plans are correctly patterned, and how the epigenome and transcriptional networks underlie these processes. The rich scientific diversity of the CDB home group allows students interested in plant biology to receive broad general training while focusing on problems critical to the proper development and physiology of plants.
CELL ORGANIZATION AND SIGNALING
Cells continually evaluate and respond to their environment. Unicellular organisms detect and move towards nutrient sources while avoiding toxic agents. In multicellular organisms, both neighboring and distal cells must communicate effectively with each other to maintain normal physiology and coordinate responses to their surroundings. Cells instruct the differentiation path of their neighbors during development, mount organized responses to infecting pathogens and form extended circuits that connect distant tissues. All of these functions are performed using signals that depend on highly specific interactions between receptor proteins and their cognate ligands. Once stimulated, receptors transduce signals throughout the cell by assembling multi-protein complexes, activating transporters and enzymes, directing traffic among subcellular compartments and regulating gene expression. Faculty members in the CDB Home Area are defining signal transduction pathways in model organisms and a variety of mammalian cell types. Many laboratories are focused on defining and circumventing cell signaling defects associated with human pathologies including cancer, nervous and immune system diseases, metabolic syndromes and developmental disorders.
In its broadest definition, metabolism includes all chemical reactions that occur within a cell. While some of these reactions cause breakdown of molecules to generate energy (catabolism), others cause synthesis of macromolecules (anabolism). CDB scientists are using the latest technologies, including metabolomics, to characterize metabolic pathways at the cellular and tissue levels in order to elucidate how they regulate normal growth, development, and homeostasis. The ultimate goal is to understand how critical cellular events such as cell-cycle progression, differentiation, senescence and death are controlled by the catabolic and anabolic reactions that occur within the organism. An understanding of these processes will shed light on the causes of disease states, such as neural degeneration and diabetes, complex disorders including cancers, and aging, for which a simple genetic basis is not available. CDB faculty interact and collaborate closely with scientists in other home areas within BSP, including Molecular Pharmacology and MCIP.
Basic and translational research in musculoskeletal biology draws a wide range of approaches, including biochemistry, genetics, molecular biology, virology, cell biology, immunology, chemistry, bioengineering, and developmental biology. Fundamental research in the mechanisms underlying the development and maintenance of musculoskeletal tissues, and in the mechanisms underlying disease pathogenesis intersect in a dynamic fashion with efforts to improve diagnosis and treatment of muscular dystrophies and skeletal diseases such as osteoporosis and arthritis. Musculosketelal tissues (muscle, bone, cartilage, and tendon) are unique in that they experience mechanical stress throughout life and depend on mechanical forces for their maintenance. A central question is: What are the signaling pathways elicited by mechanical forces that maintain the viability of musculoskeletal tissues? A related question is: Why do these pathways become deregulated during aging or in the context of disease, resulting in loss of muscle and bone mass? Other questions include: how are cells allocated to the muscle, bone, cartilage, and tendon lineages during development? And how can this information be used to direct the replacement of these tissues when they are lost due to disease, injury or aging? Musculoskeletal disorders are the leading cause of disability and pediatric disease in the United States, and because of this, record numbers of biotech and pharmaceutical companies, as well as the NIH, are investing in research in musculoskeletal biology. The goal of the Musculoskeletal Biology program is to train the next generation of leaders in basic and translational muscle, cartilage, and bone biology.
STEM CELLS & REGENERATION
Stem cells possess the ability to self-renew and differentiate to various cell types, making them critical elements in development, tissue homeostasis and repair. Faculty in CDB study stem cells in many systems, ranging from plants and animals. Decades of success in treating blood diseases by hematopoietic stem cells has provided proof-of-concept for stem cell-based therapies to treat human diseases. The derivation of human embryonic stem cells and, more recently, induced pluripotent stem cells, characterization of new tissue stem cells, and establishment of ground-breaking lineage reprogramming approaches, have raised the hope of using stem cells more broadly in therapy. Moreover, advances in high throughput technologies have provided new opportunities to uncover the regulation of stem cells and answer long-standing questions in the field: What are the cell intrinsic regulatory mechanisms that govern stem cell self-renewal and differentiation? How is stem cell fate regulated by signals from the environment? How do stem cell properties change from embryonic development to post-natal life and through aging? How do stem cells contribute to disease such as cancer? How could innovative stem cell therapies be developed to treat disease? Highly collaborative, interdisciplinary faculty in CDB work closely with faculty in other home areas to provide state-of-the-art training in stem cell biology through journal clubs, group meetings and seminar series.