The goal of the Boyden laboratory is to achieve ground truth understandings of complex biological systems, including entire cells and entire brains, and to use such insights to improve the human condition through novel inventions and therapeutics. To make this possible, Dr. Boyden and his colleagues are currently creating technologies that enable comprehensive observation and control of biological systems, aiming for molecular precision, millisecond resolution, and whole organ scale.
Biochemical analysis of the Rhesus blood group antigen led to the serendipitous discovery of AQP1, the first molecular water channel. Found throughout nature, aquaporin water channels confer high water permeability to cell membranes. AQP1 has been characterized biophysically, and the atomic structure of AQP1 is known. Identification of the Colton blood group antigen on the extracellular domain of AQP1 allowed identification of rare individuals who are AQP1-null and manifest a subclinical form of nephrogenic diabetes insipidus. Thirteen homologous proteins exist in humans.
For many years, Dr. Ley's laboratory has used mouse models of acute myeloid leukemia (AML) to establish key principles of AML pathogenesis. The lab established that the initiating event for Acute Promyelocytic Leukemia is the PML-RARA fusion gene created by the t(15;17) that is found in nearly all patients with this disease. The roles of cooperating mutations and the cellular milieu for APL pathogenesis have also been established.
We have developed the zebrafish as a surrogate model to study human tuberculosis. The optical transparency combined with the genetic tractability of this model have proved to be powerful and have allowed us to make surprising discoveries about tuberculosis pathogenesis, immunity, and drug tolerance that suggest completely new approaches to treatment. These discoveries and their application to human tuberculosis treatment will be discussed.
There is an increasing need in life and medical sciences to determine gene sequence and gene expression in cells and tissues including pathogenic organisms and viruses under normal and disease conditions as well as organismal development. The limitations in diagnostic and prognostic tools have also triggered interests in RNA present in extracellular fluid such as plasma and urine.
Primary cilia are microtubule-based organelles that are now known to be present on nearly all differentiated cell types in metazoans. Cilia house signaling molecules that transduce environmental cues and regulate cellular homeostasis and organismal development. Disruption of cilia structure or function is linked with a plethora of diseases termed ciliopathies, many of which are characterized by sensory defects.
Current research interests are focused on characterization of the structure and function of the microbial communities that are found in the human environment, as part of the NIH-funded Human Microbiome Project, including projects specifically focused on obesity, metabolic syndrome, inflammatory bowel disease, the interactions between the human immune response and the gut microbiome, and the impact of probiotics on the structure and function of the intestinal microbiome.
Dr. Zarate's current research focus is on developing novel medications for treatment-resistant depression and bipolar disorder. His areas of expertise include biological and pharmacological aspects of mood disorders in adults. Dr. Zarate's group conducts proof-of-concept studies utilizing novel compounds and biomarkers (magnetoencephalography [MEG] and polysomnography [PSG], positron emission tomography, functional MRI and magnetic resonance spectroscopy [MRS]) to identify potentially relevant drug targets and biosignatures of treatment response.
Current tools to diagnose and monitor infections are dependent upon sampling suspected sites and then performing culture or molecular techniques. This approach is invasive and is often dangerous, time consuming, and subject to incorrect sampling and contamination. Molecular imaging is a powerful, noninvasive tool that can rapidly provide three-dimensional views of disease processes deep within the body. Moreover, it has the fundamental advantage (with significant potential for clinical translation), to conduct noninvasive longitudinal assessments of the same patient.
Over the years, Dr. Germain and his colleagues have made key contributions to our understanding of Major Histocompatibility Complex (MHC) class II molecule structure–function relationships, the cell biology of antigen processing, and the molecular basis of T cell recognition. More recently, his laboratory has been focused on the relationship between immune tissue organization and dynamic control of adaptive immunity at both the initiation and effector stages.
The page was last updated on Wednesday, September 9, 2015 - 11:41am