The Systems Biology Lab applies methods of multiscale modeling to problems of cancer and cardiovascular disease, and examines the systems biology of angiogenesis, breast cancer and peripheral artery disease (PAD). Using coordinated computational and experimental approaches, the lab studies the mechanisms of breast cancer tumor growth and metastasis to find ways to inhibit those processes. We use bioinformatics to discover novel agents that affect angiogenesis and perform in vitro and in vivo experiments to test these predictions. In addition we study protein networks that determine processes of angiogenesis, arteriogenesis and inflammation in PAD. The lab also investigates drug repurposing for potential applications as stimulators of therapeutic angiogenesis, examines signal transduction pathways and builds 3D models of angiogenesis. The lab has discovered over a hundred novel anti-angiogenic peptides, and has undertaken in vitro and in vivo studies testing their activity under different conditions. We have investigated structure-activity relationship (SAR) doing point mutations and amino acid substitutions and constructed biomimetic peptides derived from their endogenous progenitors. They have demonstrated the efficacy of selected peptides in mouse models of breast, lung and brain cancers, and in age-related macular degeneration.

Dr. Raul Chavez-Valdez is an assistant professor in the Department of Pediatrics with great interest in the mechanisms of delayed injury and repair/regeneration in the developing neonatal brain following injury, specifically following hypoxic-ischemic encephalopathy (birth asphyxia). He collaborates with Dr. Frances Northington (Pediatrics) and Dr. Lee Martin (Pathology/Neuroscience) in unveiling the importance of programmed necrosis in the setting of brain injury induced by birth asphyxia. He is especially interested in the role of brain derived neurotrophic factor and neurotrophin-4 following birth asphyxia and the changes that may explain the suspected excitatory/ inhibitory (E/I) imbalance particularly in the hippocampus. His work is highly translational since delayed hippocampal injury due to E/I imbalance may explain memory deficits observed despite therapeutic hypothermia in neonates suffering birth asphyxia. All of these aspects of developmental neuroplasticity are the base of his Career Development Award (NIH/NINDS-K08 award) and applications to other agencies. Additionally, he is part of multiple clinical efforts as part of the Neuroscience Intensive Care Nursery (NICN). He has been a Sutland-Pakula Endowed Fellow of Neonatal Research since September 2013.

The Ronald Schnaar Lab is involved in the rapidly expanding field of glycobiology, which studies cell surface glycans, lectins, and their roles in cell physiology. Current projects in our lab study include (1) Glycans and glycan-binding proteins in inflammatory lung diseases, (2) Ganglioside function in the brain, and (3) HIV-Tat and HIV-associated neurocognitive disorders.

Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms. We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.

Research in the Josef Coresh Lab focuses on cardiovascular epidemiology, kidney disease and genetic epidemiology. Our team uses innovative methods to quantify disease burden and consequences in the population; studies the causes and consequences of vascular disease in the heart, kidneys and brain; and works to develop a strong scientific basis for quantifying the burden, causes and consequences of kidney disease. Working in collaboration with leading laboratories and specialists, we also aim to quantify the interplay of genes and environment in health and disease.

Research in the James Knierim Laboratory attempts to understand the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus and its inputs from the entorhinal cortex. To address these issues, we use multi-electrode arrays to record the extracellular action potentials from scores of well-isolated hippocampal neurons in freely moving rats. These neurons, or ""place cells,"" are selectively active when the rat occupies restricted locations in its environment and help to form a cognitive map of the environment. The animal uses this map to navigate efficiently in its environment and to learn and remember important locations. These cells are thought to play a major role in the formation of episodic (autobiographical) memories. Place cells thus constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an internal, cognitive representation of the world and then uses this representation as the framework that organizes and stores memories of past events.

How do we see, hear, and think? More specifically, how can we study living people to understand how the brain sees, hears, and thinks? Recently, magnetic resonance imaging (MRI), a powerful anatomical imaging technique widely used for clinical diagnosis, was further developed into a tool for probing brain function. By sensitizing magnetic resonance images to the changes in blood oxygenation that occur when regions of the brain are highly active, we can make ""movies"" that reveal the brain at work. Dr. Pekar works on the development and application of this MRI technology. Dr. Pekar is a biophysicist who uses a variety of magnetic resonance techniques to study brain physiology and function. Dr. Pekar serves as Manager of the F.M. Kirby Research Center for Functional Brain Imaging, a research resource where imaging scientists and neuroscientists collaborate to study brain function using unique state-of-the-art techniques in a safe comfortable environment, to further develop such techniques, and to provide training and education. Dr. Pekar works with center staff to serve the center's users and to keep the center on the leading edge of technology.

Dr. Jantzie, associate professor, received her Ph.D. in Neurochemistry from the University of Alberta in 2008. In 2013 she completed her postdoctoral fellowship in the Department of Neurology at Boston Children's Hospital & Harvard Medical School and became faculty at the University of New Mexico. Dr. Jantzie then joined the faculty Departments of Pediatrics (Neonatal-Perinatal Medicine) and Neurology at Johns Hopkins University and the Kennedy Krieger Institute in January 2019. Her lab investigates the pathophysiology of encephalopathy of prematurity, and pediatric brain injury common to infants and toddlers. Dr. Jantzie is dedicated to understanding disease processes in the developing brain as a means to identifying new therapeutic strategies and treatment targets for perinatal brain injury. Her lab studies neural substrates of cognition and executive function, inhibitory circuit formation, the role of an abnormal intrauterine environment on brain development, mechanisms of neurorepair and microglial activation and polarization. Using a diverse array of clinically relevant techniques such as MRI, cognitive assessment, and biomarker discovery, combined with traditional molecular and cellular biology, the Jantzie lab is on the front lines of translational pediatric neuroscience.?

Our laboratory investigates the neural bases of sound processing in the human brain. We combine electrophysiology recordings (intracranial, scalp), behavioral paradigms, and statistical modeling methods to study the cortical dynamics of normal and impaired auditory perception. We are interested in measuring and modeling variability in spatiotemporal cortical response patterns as a function of individual listening abilities and acoustic sound properties. Current studies are investigating the role of high-frequency (>30 Hz) neural oscillations in human auditory perception.

The Cochlear Neurotransmission Group studies the generation and propagation of neural signals in the inner ear. Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells ('hair cells') to excite second order neurons carrying information to the brain. We apply these same techniques to study inhibitory feedback produced by brain neurons that project to and regulate the sensitivity of the cochlea.