Human Physiology Labs
A list of Human Physiology labs and research are featured below.
Cytoskeleton & Signaling Laboratory
Our goals are understanding and finding new therapies for cardiovascular disease, the number one killer in America. We focus primarily on the contractile smooth muscle cells that comprise a large portion of the walls of blood vessels. In collaboration with researchers at BU School of Medicine, we’re trying to determine why blood vessels—particularly the aorta—stiffen with age. Since the cardiovascular diseases that can follow are currently irreversible, preventing this vessel stiffening would be a life-changing advance.
We are one of relatively few labs with expertise in the mechanisms of contractile function of vascular smooth muscle cells (VSMCs). Among our achievements, we were responsible for the first calcium measurements in vascular smooth muscle—the basis for calcium channel blockers such as anti-hypertensives. We do extensive work with smooth muscle proteins, hoping that one of them could serve as a target molecule for the reversal of aging-induced aortic stiffness.
Human Systems Neuroscience Laboratory
Human Systems Neuroscience Laboratory
Director: Basilis (Vasileios) Zikopoulos
Research in the Human Systems Neuroscience Laboratory focuses on the study of the organization and dynamics of cortical brain circuits, and their disruption in disease. Increasingly, our work has been focusing on processes that shape network dynamics and the delicate balance of excitation and inhibition, which are consistently disrupted in autism and other neurodevelopmental disorders.
We use advanced experimental and computational approaches to image and study molecular, synaptic, cellular interactions and interareal network connectivity, as the basis of cognitive and emotional processing for flexible attention and goal-oriented behavior in humans, non-human primates and other relevant animal model systems. Our innovative multi-disciplinary approach includes correlated light, confocal and electron microscopy; and large-scale, and thus far unprecedented, three-dimensional analysis and reconstruction of labeled pathways and their synaptic and neurochemical interactions within functionally-distinct networks.
These cutting-edge, high-resolution experimental approaches, complemented by advanced computational and image analysis techniques, have made it possible to conduct detailed quantitative analyses and develop brain-based circuit and computational models, describing novel circuits that have a key role in cognitive and emotional processes. This experimental and theoretical framework that helps us derive principles from complex data on connections and their interactions provides a solid foundation to integrate bench and clinical research across neuroscience disciplines.
Muscle Biology Laboratory
Muscle Biology Laboratory
Director: Susan Kandarian
Muscle wasting is a widespread health problem characterized by weakness, fatigue, glucose intolerance, and an inability to tolerate medicines to treat illness. There has been a pressing need to comprehend the biology underlying this process. Our laboratory uses cellular and molecular approaches to better understand the pathways that mediate protein loss associated with skeletal muscle wasting. Studies are geared toward identifying genes that are necessary or sufficient for the induction and progression of skeletal muscle atrophy in conditions such as muscular disuse and cancer-induced muscle wasting. Recently we have adapted a new technology called “ChIP-sequencing” (chromatin immunoprecipitation followed by next generation sequencing) to skeletal muscle in order to identify, on a genome-wide level, the genes responsible for muscle wasting due to muscular inactivity. The networks of genes we identified using ChIP-sequencing show how inactivity leads to muscle weakness and the insulin resistance that foreshadow type 2 diabetes. These findings, using a cutting-edge technology, identify genes regulating skeletal muscle wasting that years of traditional methods have failed to discover.
Muscle Disorders and Regenerative Biology Laboratory
Our lab works with MDC1A, a congenital and often lethal form of muscular dystrophy for which there is no cure. We work with muscle signaling to understand the molecular mechanisms of muscle diseases in general and identify therapeutic targets for this disease in particular. Our research is at the forefront of efforts to improve longevity and quality of life for those with muscular dystrophy.
While most treatments are single-target therapies, we have recognized that this is a multi-target disease and are delving into combinations of different therapies to target multiple pathways. Our work has shown that both programmed cell death and limited regenerative capacity are important drivers of MDC1A’s pathogenesis. In our recent studies, targeting these two pathological mechanisms together resulted in marked improvement of the muscle pathology. Strategies developed by our lab are now being considered by clinicians for use in clinical trials.
Neural Systems Laboratory
The Neural Systems Lab specializes in the organization of the prefrontal cortex and its role in central executive functions in primates. Our research objective is to investigate prefrontal pathways that interface with both excitatory and inhibitory neurons in cortical and subcortical structures, possibly providing the basis for selecting relevant information and suppressing irrelevant information in primate behavior.
The use of neural tracers to label pathways, combined with a multi-modal approach, makes our work cutting-edge. We use histochemical, immunocytochemical, and molecular procedures; quantitative approaches and imaging; and multidimensional analyses.
Quantitative Neuroscience Laboratory
Our lab aims to understand the brain’s fundamental architecture, with particular interest in speech and language. While we are primarily a computational lab, we use an innovative multidisciplinary, multi-modal approach, combining computational, informatics, and experimental methods. Among these is functional MRI brain imaging to measure activity related to specific tasks. We are one of the few groups working to connect genetic and neurological brain imaging datasets in meaningful ways. This research has long-term applications to drug discovery and therapeutic applications for neuropsychiatric or neurological disorders.
In addition to collecting data, we analyze existing large datasets to discover new patterns related to brain architecture. We also collaborate on groundbreaking interdisciplinary projects such as the Mouse Brain Architecture Project. This effort to create the first comprehensive neural connectivity map of the mouse brain could have wide-ranging implications for human brain mapping.
Claus C. Hilgetag: Brain Networks Laboratory
Jacobs University School of Engineering and Science
Our lab is focused on studying various aspects of brain connectivity. Specifically, we use statistics and neuroinformatics to establish the characteristic organization of brain networks and explore the implications of this organization for brain dynamics and function through computational modeling. We believe brain dynamics and function need to be understood in the context of the brain’s complex network organization.
We are using a very wide range of approaches, from neuroinformatics (done in close collaboration with experimental neuroanatomists, particularly the Barbas lab at BU Health Sciences) and computational modeling of brain dynamics to experimental studies of brain modulation by transcranial magnetic stimulation (TMS), in order to understand from several different perspectives ‘how the brain works.’
We have students with a wide range of backgrounds, from biology and psychology to physics and computer science—reflecting the diverse techniques and approaches that are employed in modern neuroscience. Most of our graduates stay in academia, and have established their own labs by now.
As part of our research, we also study the consequences of lesions in brain networks, using ‘virtual lesions’ (produced by TMS) as well as computational modeling.
Peter Kang: Basic and Translational Cardiovascular Research Laboratory
Cardiovascular Institute, Beth Israel Deaconess Medical Center
The major focus of our laboratory is basic and translational cardiovascular research with an emphasis on developing novel therapies for cardiovascular diseases. One of our research interests is to study the molecular mechanisms of cardiac apoptosis (programmed cell death) and develop new anti-apoptotic applications in cardiovascular diseases. One of the ways in which heart muscle is injured following a loss of blood supply (as in a myocardial infarction, or heart attack) occurs when blood reenters, or reperfuses, the tissue. This results in a cascade of events, including the release of free radicals and the initiation of apoptosis. Hydrogen peroxide is the most abundant free radical produced during reperfusion injury.
Our work is highly innovative, in that we are using nanotechnology to design and engineer molecules that are selectively activated by the hydrogen peroxide released during reperfusion injury. The beauty of this system is that therapeutic substances engineered into the nanoparticles are released only at the site of the injury, rather than being distributed throughout the entire body. This same system could also be exploited to image the damaged tissue.
In a second project, we showed that Vitamin D therapy prevents the progression of cardiac hypertrophy and heart failure in animal models. We are currently investigating the molecular mechanism of cardiac dysfunction associated with Vitamin D deficiency and examining the potential role of Vitamin D therapy in the treatment of heart failure. Also, in collaboration with other investigators, we identified novel Vitamin D receptor agonists and are studying these novel compounds for clinical applications.
Lisa Leon: Hyperthermia Research Laboratory
United States Army Research Institute of Environmental Medicine
We focus on identifying the mechanisms that mediate systemic inflammatory response to heat stroke. Specifically, our objective is to identify new biomarkers in the circulation that reflect inflammatory changes occurring in organs during heat stroke recovery. To accelerate the process of finding pathways that mediate injury, we use a novel, systems biology approach, collaborating with mathematical modelers who develop predictive models for identifying biomarkers and molecular targets. We can then test these targets in our experimental models—the only ones that currently enable the examination of physiological, biochemical, and molecular changes through long-term heat stroke recovery.
We’re also interested in finding new pharmacologics that can be used to treat heat stroke. Currently, there are no scientifically validated diagnostics or pharmacologic treatments.
Katya Ravid: Blood and Vascular Pathologies Laboratory
Katya Ravid Lab Website
Boston University School of Medicine
Our lab is conducting investigations in the area of blood and vascular pathologies. The cells of all blood lineages arise from pluripotent hematopoietic stem cells that reside in the marrow. The bone marrow also contains stem cells of other lineages, including fat, vascular etc. Our research is focused on two interrelated projects that bear on mechanisms associated with the development of blood and vascular pathologies: (1) molecular mechanisms involved in bone marrow megakaryocyte/platelet development; (2) the role of vascular and bone marrow cell (mesenchymal stem cells) adenosine receptors in tissue regeneration. Transgenic and knockout mouse models are used to assist in exploring mechanisms in vivo.