The Jun O. Liu Laboratory tests small molecules to see if they react in our bodies to find potential drugs to treat disease. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases. Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation.

The Seth Margolis Laboratory studies the signaling pathways that regulate synapse formation during normal brain development to try to understand how, when these pathways go awry, human cognitive disorders develop. We use Ephexin5 to study the molecular pathways that regulate restriction of excitatory synapse formation and their relevance to the pathophysiology of Angelman syndrome.

Dr. Borahay's lab focuses on understanding pathobiology, developing novel treatments, and carrying out high quality clinical trials for common gynecologic problems with a special focus on uterine fibroids. Our lab also investigates the causes and novel treatments for menstrual disorders such as heavy and irregular periods. In addition, Dr. Borahay’s team explores innovative approaches to minimally invasive gynecologic surgery, focusing on outpatient procedures with less pain and faster recovery times.

Researchers in the Center for Cell Dynamics study spatially and temporally regulated molecular events in living cells, tissues and organisms. The team develops and applies innovative biosensors and imaging techniques to monitor dozens of critical signaling pathways in real time. The new tools help them investigate the fundamental cellular behaviors that underlie embryonic development, wound healing, cancer progression, and functions of the immune and nervous systems.

The Wong Lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic homeostasis. We are currently addressing how adipose- and skeletal muscle-derived hormones (adipokines and myokines), discovered in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use transgenic and knockout mouse models, as well as cell culture systems, to address the role of the CTRP family of hormones in physiological and disease states. We also aim to identify the receptors that mediate the biological functions of CTRPs.

The Nicholas Flavahan Lab primarily researches the cellular interactions and subcellular signaling pathways that control normal vascular function and regulate the initiation of vascular disease. We use biochemical and molecular analyses of cellular mediators and cell signaling mechanisms in cultured vascular cells, while also conducting physiological assessments and fluorescent microscopic imaging of signaling systems in isolated blood vessels. A major component of our research involves aterioles, tiny blood vessles that are responsible for controlling the peripheral resistance of the cardiovascular system, which help determine organ blood flow.

The Glunde lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab is developing mass spectrometry imaging as part of multimodal molecular imaging workflows to image and elucidate hypoxia-driven signaling pathways in breast cancer. They are working to further unravel the molecular basis of the aberrant choline phospholipid metabolism in cancer. The Glunde lab is developing novel optical imaging agents for multi-scale molecular imaging of lysosomes in breast tumors and discovering structural changes in Collagen I matrices and their role in breast cancer and metastasis.

The Pomerantz Laboratory studies the molecular machinery used by cells to interpret extracellular signals and transduce them to the nucleus to affect changes in gene expression. The accurate response to extracellular signals results in a cell's decision to proliferate, differentiate or die, and it's critical for normal development and physiology. The dysregulation of this machinery underlies the unwarranted expansion or destruction of cell numbers that occurs in human diseases like cancer, autoimmunity, hyperinflammatory states and neurodegenerative disease. Current studies in the lab focus on signaling pathways that are important in innate immunity, adaptive immunity and cancer, with particular focus on pathways that regulate the activity of the pleiotropic transcription factor NF-kB.

Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventing maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task.

The Barouch Lab is focused on defining the peripheral cardiovascular effects of the adipocytokine leptin, which is a key to the understanding of obesity-related cardiovascular disease. Interestingly, many of the hormonal abnormalities seen in obesity are mimicked in heart failure. The research program will enhance the understanding of metabolic signaling in the heart, including the effects of leptin, exercise, sex hormones, and downstream signaling pathways on metabolism and cardiovascular function. The lab also is working to determine the precise role of the “metabolic” beta-3 adrenergic receptor (ß3AR) in the heart and define the extent of its protective effect in obesity and in heart failure, including its role in maintaining nitric oxide synthase (NOS) coupling. Ultimately, this work will enable the exploration of a possible therapeutic role of ß3AR agonists and re-coupling of NOS in preventing adverse ventricular remodeling in obesity and in heart failure. Lili Barouch, MD, is an associate professor of medicine in the Division of Cardiology and a member of the Advanced Heart Failure and Cardiac Transplantation group at the Johns Hopkins University School of Medicine.