Our lab evaluates new medications and/or techniques for the treatment of drug use disorder by conducting human laboratory studies to sensitively assess drug effects, and randomized controlled trial evaluations of medications for clinical treatment outcomes. We also focus on the development of outcome measures that are sensitive and clinically relevant.

The Mohamed Farah Lab studies axonal regeneration in the peripheral nervous system. We've found that genetic deletion and pharmacological inhibition of beta-amyloid cleaving enzyme (BACE1) markedly accelerate axonal regeneration in the injured peripheral nerves of mice. We postulate that accelerated nerve regeneration is due to blockade of BACE1 cleavage of two different BACE1 substrates. The two candidate substrates are the amyloid precursor protein (APP) in axons and tumor necrosis factor receptor 1 (TNFR1) on macrophages, which infiltrate injured nerves and clear the inhibitory myelin debris. In the coming years, we will systematically explore genetic manipulations of these two substrates in regard to accelerated axonal regeneration and rapid myelin debris removal seen in BACE1 KO mice. We also study axonal sprouting and regeneration in motor neuron disease models.

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.

Research in the Meredith McCormack Lab deals primarily with pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and the role of environmental exposures in lung diseases. We have researched the factors that contribute to inner-city asthma, with a focus on how particulate matter air pollution impacts pulmonary function. We are also part of the LIBERATE clinical study, which is focused on patients who experience difficulty breathing and have been diagnosed with severe emphysema. We also have a longstanding interest in the effects of race/ethnicity, poverty and urbanization on nutrition and food allergies.

Dr. Fridman's research group invents and develops bioelectronics for Neuroengineering and Medical Instrumentation applications. We develop innovative medical technology and we also conduct the necessary biological studies to understand how the technology could be effective and safe for people. Our lab is currently focused on developing the ""Safe Direct Current Stimulation"" technology, or SDCS. Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, SDCS can excite, inhibit, and even sensitize them to input. This new technology opens a door to a wide range of applications that we are currently exploring along with device development: e.g. peripheral nerve stimulation for suppressing neuropathic pain, vestibular nerve stimulation to correct balance disorders, vagal nerve stimulation to suppress an asthma attack, and a host of other neuroprosthetic applications. Medical Instrumentation MouthLab is a ""tricorder"" device that we invented here in the Machine Biointerface Lab. The device currently obtains all vital signs within 60s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.

Work in the Marek Mirski lab explores the subcortical mechanisms of seizure propagation and cortical synchrony. The primary goal of our research is to develop methodologies for inhibiting seizures using site-specific subcortical electrical stimulation. Our identification of synaptically linked subcortical elements that contribute to seizure propagation has led to FDA-sanctioned phase III clinical trials to assess the use of targeted thalamic stimulation in patients with intractable seizures. We also conduct clinical research on the treatment of acute head injury, elevated intracranial pressure, cerebral edema, ischemic stroke and ICU sedation.

The Penet lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab research focuses on using multimodal imaging techniques to better understand the microenvironment and improve cancer early detection, especially in ovarian cancer. By combining MRI, MRS and optical imaging, we are studying the tumor microenvironment to understand the role of hypoxia, tumor vascularization, macromolecular transport and tumor metabolism in tumor progression, metastasis and ascites formation in orthotopic models of cancer. We also are studying the role of tumor-associated macrophages in tumor progression.

Our broad research goals are to identify and validate novel molecular therapeutic targets in hematopoietic malignancies. We are interested in the identification and pre-clinical development of novel targeted therapies, and, in particular, the “translational” step of this research by using correlative studies to incorporate these novel therapies into existing treatments. Our research is of particular interest to those who wish to be involved in directly translating the results of laboratory bench work into meaningful benefits for patients. Currently, we are actively involved in the pre-clinical and clinical development of small molecule kinase inhibitors targeting the FLT3 signaling pathway in acute myeloid leukemia. We are interested in 3 compounds in particular- AC220, a FLT3/KIT inhibitor; crenolanib,a selective FLT3 inhibitor with activity against resistant point mutations; and PLX3397, another inhibitor of KIT and FLT3. The active projects in the lab include: 1) Characterization of cytotoxic responses of different hematologic malignancies to FLT3 and KIT kinase inhibition; 2) Examination of the interaction of bone marrow stroma and stroma-derived cytokines on the efficacy of these inhibitors; 3) Examination of the differential effect of FLT3 inhibition versus combined FLT3/KIT inhibition on acute myeloid leukemia and bone marrow progenitor cells; and 4) Correlative laboratory studies using blood and marrow samples from patients treated with FLT3 inhibitors, with the aim of developing predictive models for clinical response.

Work in the Mahendra Damarla Lab focuses primarily on the field of vascular biology. Much of our research involves exploring alternatives to mechanical ventilation as a therapy for acute lung injury. We investigate mitogen-activated protein kinase-activated protein kinase 2 as a method to mediate apoptosis during lung vascular permeability by regulating movement of cleaved caspase 3. We have also conducted research on the prevalence of confirmatory tests in patients hospitalized with congestive heart failure or chronic obstructive pulmonary disease (COPD).

Research interests in the Marcia Canto Lab include pancreatic neoplasms, Barrett’s esophagus and endomicroscopy. We are also interested in the use of endoscopic ultrasound to identify early-stage pancreatic cancer and its precursors.