Ming Zhang, Ph.D - US grants

DESCRIPTION (provided by applicant): Myocardial infarction (MI) is a leading cause of mortality in today's society. Injury to myocardium is a manifestation of the intrinsic cellular response to ischemia and of an extrinsic acute inflammation. Recent pre-clinical studies have revealed that pre-existing natural IgM functions as the critical mediator between the intrinsic and extrinsic responses in injury induction. The goal of this proposal is to expand these novel basic science discoveries at the clinical level. Knowledge gained from this study will provide a new basis for clinical management of myocardial infarction. The specific aims are as follows: Aim 1. To determine whether natural IgM antibodies against an ischemia-specific self antigen (non-muscle myosin heavy chain II, NMHC-II) are present in normal individuals and patients with acute myocardial infarction. Aim 2. To investigate whether the levels of these autoimmune antibodies correlate with the degrees of myocardial injury. PUBLIC HEALTH RELEVANCE This study will provide important insight of a new mechanism in ischemic myocardial injury, and may identify new markers for myocardial infarction.

The Principal Investigator's (PI's) team will calculate the injection and acceleration of solar energetic particles (SEPs) caused by shock wave events associated with coronal mass ejections (CMEs). The proposing team will use a three-dimensional magnetohydrodynamic model of CME shocks to trace the evolution of these shock waves in a realistic manner and to calculate the SEP source particle distribution in space. The team will obtain the temporal and spatial variation of SEP source intensity and spectra in the solar corona, and input this data into their three-dimensional interplanetary particle transport model for calculation of SEP intensity at Earth and other locations in the solar system.

The PI states that the results of this study will assist the development of improved space weather tools to forecast the near-Earth space radiation environment resulting from solar events. The PI also notes that particle injection and acceleration by shock waves is one of the great unsolved problems in space physics and astrophysics. This investigation of particle acceleration and transport in the solar system will enhance our understanding of many other high-energy astrophysics phenomena in the universe (such as cosmic rays, supernova remnants, and gamma-ray emissions). In addition, the project will provide training to a young postdoctoral scientist.

Electromagnetic ion cyclotron (EMIC) waves are a common feature of the Earth's magnetosphere and strongly affect ions, thermal electrons, and thermal/suprathermal ions in ring current. EMIC waves also play in important role in the formation and loss of relativistic electrons in the outer radiation belt. This project will use a combination of observational data and theoretical modeling to obtain the EMIC wave power spectral density (PSD) on a global magnetospheric scale. The project will examine how the EMIC PSD develops throughout the different phases of geomagnetic storms. It will use a quasi-linear approach to the Ring Current-EMIC wave system that is based on a set of the kinetic equations that self-consistently treat the coupling of the ring current and EMIC waves. The model will be a development and enhancement of existing model. The major tasks will be (1) to develop a self-consistent, non-bounce-averaged, model of EMIC waves in the magnetospheric plasma, (2) to include a self-consistent magnetic field calculation in the global RC model, (3) to verify the modeled EMIC waves against the observational data from the Cluster satellite mission.

This project is relevant to NSF's Geospace Environment Modeling (GEM) program. It will proved a self-consistent model of processes that are important in space weather and will enhance our ability to forecast space weather phenomena in the ring current and out radiation belt. The project has educational impacts as well. An undergraduate student will be trained and involved in this study.

? DESCRIPTION (provided by applicant): Ischemia followed by reperfusion (IR), which occurs unavoidably during organ transplantation, elicits immune responses that contribute to graft dysfunction. Delineating novel, effective therapies to prevent IR injury has the potential to change clinical practice and improve patient health following organ transplantation. The goals of this project are to define the role of complement factor B (fB) in post-transplant injury, identify new mouse and human fB antagonists and begin to test them in animal models. The long term goal is to use the inhibitors to prevent allograft injury in humans. Our combined published and preliminary data demonstrate that: blocking complement activation in a donor organ prolongs allograft survival in mice; fB gene expression is increased in biopsies of heart transplantation patients compared with levels in normal heart tissue, and correlates with graft rejection grades; in a murine myocardial IR model, injury is significantly reduced in fB-/- mice; fB is significantly activated in the hearts of patients undergoing open heart surgery, i.e., experiencing surgically-induced global heart ischemia; in these patients, the levels of Bb, the activated fB fragment, correlate with the post- surgical increase of circulating cardiac troponin I, a marker of myocardia injury. Thus, fB expression and activation in donor organs are important in graft rejection. The specific aims are: 1) To identify small peptide antagonists specific for murine and for human fB using a phage display peptide library. 2) To determine the role of fB in transplant rejection in mice and to test the efficacy of fB inhibition. We expect that the studies will identify novel fB inhibitors, provide new insight into mechanisms of IR injury and transplant rejection, and provide preclinical data to support human studies to block fB in vivo.