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The visual aspects of MS

  • Laura Balcer, MD, MSCE, Professor of Neurology
  • $1.3 million
  • Vision problems are relatively common in people with multiple sclerosis (MS). Inflammation and loss of nerve cell axons in the optic nerves, retina, chiasm, and tracts can lead to permanent visual loss. This project is a three-center collaboration to perform a long-term study to evaluate these problems and look for better outcomes for MS patients. Non-invasive imaging of the eye is now recognized in MS as a potential marker for nerve loss due to inflammation. This study will look at how best to incorporate these techniques into upcoming MS clinical trials and treatment paradigms.
  • Support for study coordinators and technicians who do vision testing and OCT (eye) scanning

Biomarkers of toxic response to low nicotine cigarette smoke

  • Ian Blair, PhD, A. N. Richards Professor of Pharmacology
  • Andrew Strasser, PhD Assistant Professor of Psychiatry
  • $1.3 million
  • It's the 3,800 chemical components of tobacco smoke that make it a leading cause of death in America. Associated with cardiovascular disease, chronic obstructive pulmonary disease, and pancreatic disease, tobacco smoke is likely responsible for more deaths than any other environmental exposure. Blair and Strasser aim to look for biomarkers of exposure to cigarette smoke and biobehavioral aspects of cigarette smoking, hoping to determine whether low nicotine cigarettes are more dangerous than regular cigarettes.
  • Support for six (Database Technician, 1 Project Coordinator, 1 Smoking Technician, 3 Post Doctoral Fellows) as well as partial support for the Co-PIs (Drs. Blair and Strasser) and Dr. Andrea Troxel, the biostatistician

The molecular biology of MS

  • Youhai H. Chen, MD, PhD, Professor of Pathology and Laboratory Medicine
  • $500,000 direct costs for two years.
  • Autoimmune diseases afflict millions of people and are the fourth largest cause of disability among women in the US. This project will study the molecular mechanisms through which a molecule called c-Rel causes autoimmune encephalomyelitis, an animal model for multiple sclerosis. The researchers will test the hypothesis that c-Rel regulates autoimmune encephalomyelitis by promoting the development of T-helper-17 cells, disease-causing cells involved in autoimmune diseases. The first set of data has been generated using cells from mice, indicating that c-Rel is crucial for Th17 cell development.
  • Support for research assistants

Regulation of immune tolerance

  • Yongwon Choi, PhD, Professor of Pathology and Laboratory Medicine
  • $1.3 million
  • Immune tolerance happens when the body does not mount an immune response to self antigens. Genetic defects in these processes lead to autoimmunity. This award will aid continued studies of the molecular and cellular regulation of immune tolerance. The outcome of this study may contribute to preventing or treating such autoimmune diseases as arthritis and inflammatory bowel disease.
  • Support for postdocs and technicians who have been involved in this project

Minimizing brain damage during heart surgery

  • David M. Eckmann, PhD, MD, Horatio C. Wood Professor of Anesthesiology and Critical Care
  • $907,262
  • Unwanted gas bubbles in the bloodstream during heart surgery contribute to brain damage in over 300,000 cardiopulmonary bypass patients in the US annually. Bubbles also promote clot formation, leading to stroke. The team will study drug therapies to minimize brain injury by looking at small molecules that stick to bubbles entering the bloodstream, with the aim of dissipating the bubbles before they enter the brain.
  • Support for two postdoctoral fellows and a technician

The healthcare system and autism

  • David S. Mandell, ScD, Assistant Professor of Psychiatry
  • $171,947
  • This research aims to find the best ways to improve the organization, financing, and delivery of healthcare and education services to people with autism. This new supplement will provide much-needed support in analyzing, interpreting and writing up the results of a 50-state study of Medicaid-reimbursed healthcare utilization among children with autism.
  • Support for a postdoctoral fellow

Sonic hedgehog and development

  • David Manning, PhD, Professor of Pharmacology
  • $315,072
  • Sonic hedgehog is a protein that plays an essential role in embryonic development and tissue regeneration. Problems in molecular signaling caused by this protein lead to developmental defects, while unrepressed signaling leads to several cancers. A complete understanding of the mechanisms by which Sonic hedgehog signals can be mimicked will provide important leads into how that signaling might be manipulated to develop new treatments. This award will concentrate on the precise role for a family of molecular switches called G proteins that interact with Sonic hedgehog and the need to evaluate G proteins in normal and dysregulated processes.
  • Support for one postdoc and one technician

Mutations in transporter proteins and rare diseases

  • Surafel Mulugeta, PhD, Research Assistant Professor of Medicine, Pulmonary, Allergy & Critical Care Division
  • $291,795
  • The breakdown of organs due to gene mutations resulting in misfolded proteins remains largely undefined. This project looks at how different mutations in a family of proteins called ABCA transporters, which are structurally and functionally similar, ultimately cause disease. Their mutations are linked to rare and severe inherited human disorders including Tangier disease/HDL deficiency (ABCA1), fatal respiratory distress syndrome and interstitial lung disease (ABCA3), Stargardt disease (ABCA4), and Lamellar/Harlequin ichthyosis (ABCA12). This project aims to determine common mechanisms of how mutations in these transporters cause lung disease such as pediatric/adult interstitial pulmonary disease and other organ dysfunctions.
  • Support for one postdoctoral fellow

Reining in unwanted calcium in blood vessels of dialysis patients

  • Sylvia Rosas, MD, Assistant Professor of Medicine, Renal Electrolyte and Hypertension Division
  • $108, 510
  • Patients with chronic kidney disease on dialysis have an annual mortality rate of 20%. Cardiovascular disease accounts for approximately 50% of deaths in these patients. They have an atypical form of atherosclerosis with increased deposition of calcium in the blood vessels. Recent evidence suggests that a chronic inflammatory state and alterations of bone mineral metabolism may play an important role in this calcification process. This project will enroll 125 asymptomatic new-start dialysis patients and obtain measurements of calcification to identify modifiable risk factors for progression of calcification to be used in future randomized clinical trials. Also, it aims to give insight on whether current clinical therapies are increasing calcification in dialysis patients.
  • Support for one clinical research coordinator

Understanding platelet proteins' role in heart disease

  • Bruce Sachais, MD, PhD, Assistant Professor of Pathology and Laboratory Medicine; Director of Transfusion Services, HUP
  • $170,374
  • When the body is bruised or cut, blood platelets take over to help repair vessels, skin, and other tissues. But there is increasing evidence that this activation of platelets plays a role in the build up of fatty deposits on blood vessel walls called atherosclerosis, which leads to heart attacks and strokes. A platelet protein called PF4 has been implicated in this process. The team aims to find out how PF4 promotes atherosclerosis and suggest potential ways to intervene.
  • Support for research technicians

Improving nicotine patches

  • Robert A. Schnoll, PhD, Associate Professor of Psychiatry
  • $433, 125(total costs)
  • The transdermal patch is the most widely used form of tobacco dependence treatment in the US, but abstinence rates following nicotine patch treatment are only about 9% after 12 months. One reason may be that people metabolize nicotine differently and therefore patches are not uniformly effective. This research aims to determine, among fast metabolizers of nicotine, whether high-dose nicotine patches are more effective for quitting smoking, vs. standard patches. This developmental, exploratory study will lay the groundwork for a full clinical trial of high-dose transdermal nicotine patches for fast metabolizers of nicotine.
  • Support for a research assistant and smoking cessation counselor

How do viruses induce hepatitis?

  • Susan Weiss, PhD, Professor of Microbiology
  • $275,000
  • Viruses can interact with liver cells, sometimes leading to hepatitis. These researchers will use a murine coronavirus -- mouse hepatitis virus (MHV) -- that induces hepatitis in a strain-specific manner, to evaluate both viral genetic determinants and host intrahepatic innate immune responses underlying pathogenesis. Elucidation of the mechanism of MHV-induced hepatitis will contribute to the understanding of hepatitis in humans and in the long term contribute to the design of anti-viral therapies.
  • Support for one postdoc position and one half-time research specialist position