Rensselaer Mount Sinai Collaborative Research Projects-Applications Request

The Rensselaer Mount Sinai Collaborative Research Projects received twenty nine project proposals of which seven were selected for Pilot Funding Awards

Collaborative Research Projects 2013

1. Effects of retrotransposons on genome instability and consequence for the biology of aging and cancer (M. O'Connell P. Maxwell)

Changes in DNA sequences that result when cells experience problems copying their DNA are associated with aging and cancer. This project seeks to determine the consequences of problems that arise during the copying of DNA due to a specialized type of DNA sequence, and how cells try to protect themselves from these problems. The overall intent is to identify specific processes in cells that could become targets of future therapies to promote healthy aging and treat/prevent tumor formation. The goals of the project will be efficiently addressed by utilizing simple research organisms, yeasts, which can provide information relevant to human cells. Furthermore, the project will foster collaboration between researchers at Mount Sinai and Rensselaer Polytechnic Institute, particularly regarding DNA sequencing, so that the strengths of both institutions can be applied in future projects that address significant biomedical research topics.

2. In situ generation of tissue-engineered vascular conduits using vascular progenitor cells (J. Kovacic & M. Hahn)

Cardiovascular disease (CVD) is the cause of heart attacks and strokes, and accounts for 40% of US deaths. One important way of treating CVD is by "bypass surgery". In this procedure, a special "vascular graft" is made to "bypass" any blockages in the heart arteries. As well as this, there are also many other medical uses for vascular grafts in the body, such as for dialysis patients. However, a major problem at the moment with these vascular grafts is that they often become blocked after a short time. This is a huge medical problem and can cause a lot of discomfort and suffering for patients. In this project, we plan to try to develop ways to make better quality vascular grafts that will last better and stay open for longer. We will do this by combining our knowledge of vascular stem cells with advanced techniques for making vascular grafts in the laboratory. This research of very major medical importance, as it could lead to better treatments for patients with blockages in the heart arteries and other medical problems.

3. Inhibiting hepatitis C virus with high affinity single-domain antibodies (M. Evans & P. Tessier)

The hepatitis C virus (HCV) is responsible for the majority of liver cancer in the Western Hemisphere. Current HCV therapies are often ineffective, associated with severe side effects, and elicit viral resistance. Here we propose experiments to use the Tessier lab's expertise in developing antibodies and the Evans lab's expertise in the HCV cell entry process to develop inhibitors against this stage of the viral life cycle. Numerous cellular factors, including the tight junction protein occludin (OCLN), are required for HCV cell entry. Our long-term goal is to develop new agents that inhibit HCV cell entry as potential anti-HCV therapies. The overall objective of this application, which is the next step toward attaining this goal, is to develop antibodies bearing regions of OCLN that make high-affinity interactions with the E2 glycoprotein of the HCV virion. We hypothesize that such antibodies will inhibit HCV infection by competitively blocking binding of the virion with OCLN on the host cell.

4. Proteoglycan metabolism and painful intervertebral disc degeneration (J. Iatridis & R. Linhardt)

Painful intervertebral disc (IVD) degeneration is implicated in the pathogenesis of chronic low back pain which affects approximately 80% of the global population. The earliest compositional change in IVD degeneration is the substantial proteoglycan loss, associated

5. Toward a Universal Influenza Virus Vaccine: Development of Nanoscale Constructs that Elicit Broadly Neutralizing Antibodies (P. Palese & R. Kane)

Inactivated influenza virus vaccines induce an immune response against the membrane-distal globular head domain of the viral hemagglutinin (HA). Antibodies directed against this region are highly neutralizing but, due to the high plasticity of this domain, strain specific. Antibodies against the highly conserved, membrane distal stalk domain of the HA are rare in nature and not induced by regular influenza virus vaccines. However, these antibodies have been isolated from mice and humans and show broad neutralization activity across influenza virus strains and subtypes. A vaccine that induces high titers of these cross-protective antibodies might therefore provide universal influenza virus protection. Here we will utilize nanoscale scaffolds as a vaccine platform to induce such broadly neutralizing antibodies. The nanoscale scaffolds will be produced and tested by the Kane group at Rensselaer Polytechnic Institute while antigen engineering will be performed by the Palese group at Mount Sinai. In a joined effort we will characterize and test the immunogenicity of the constructs and develop plans for future funding based on the results. Our approach has the potential to lead to the development of a universal influenza virus vaccine that would further enhance our pandemic preparedness and might abolish the need for annual re-formulation of influenza virus vaccines.

6. Continuous Monitoring of Compartmental Pressures for Objective Diagnosis of Compartment Syndrome (D. Forsh, J. Gladstone, E. Ledet, & K. Connor)

Compartment syndrome can be a devastating consequence secondary to extremity fractures. Missed diagnosis can lead to amputation. With this research, we are evaluating a novel technology to determine its efficacy for early and objective detection of compartment syndrome. If efficacious, the technology will be further evaluated for clinical use.

7. Inducing targeted mutations in cells in the brain in vivo (Can dopamine transporter be modified to resist drug abuse) (E. Nestler & S. Kotha)

The goal of the project is to determine if nano-particulate delivery technology can be used to induce targeted mutations in cells constituting the brain.