Biomedical Engineering Graduate Student Seminar

Time: Thursday, April 24, 2014 - 4:00pm - 5:00pm
Type: Seminar Series
Presenter: Graduate Students: Jean Huang (James Duncan and Lawrence Staib) & Michael McHugh (Tarek Fahmy)
Room/Office: Becton Seminar Room
Becton Seminar Room
15 Prospect St
New Haven, CT
United States

Biomedical Engineering Graduate Seminar Series

Date: Thursday, April, 24th
Time: 4 pm
Location: Becton Seminar Room
Speakers (Advisors): Jean Huang (Jim Duncan) & Michael McHugh (Tarek Fahmy)
Reminder: Attendance for all graduate students is compulsory
The titles and abstracts for the two talks are below. Food and drinks will follow the seminar.

Speaker: Jean Huang (James Duncan and Lawrence Staib)
Title: White Matter Parcellation from DWI using Dictionary Learning
Abstract: Magnetic resonance diffusion weighted imaging (DWI) is an in vivo and noninvasive method to quantify the diffusion of water molecules in biological tissues, and a commonly used way to study the tissue microstructure of the brain. White matter parcellation methods use the orientation and strength of the anisotropy of water diffusion in neuronal fibers to estimate white matter tracts in the brain. Many algorithms have been proposed in recent years to parcellate white matter, but few use region-based active contour methods to segment tracts, or incorporate prior shape or appearance information. Moreover, most of these methods perform segmentation based on scalar measures rather than incorporating directionality information from the whole diffusion tensor. We propose a segmentation method using sparse representation and dictionary learning on the diffusion tensor, integrating directionality and shape as well as intensity information from our priors. Applications of this project include the development of structurally-informed, DTI-based neuroimaging methods to quantify the connectivity of neural subnetworks. These measures can serve as imaging biomarkers to aid in the characterization of neurological disorders such as autism.

Speaker: Michael McHugh (Tarek Fahmy)
Title: Induction of Immunological Tolerance with Biodegradable Immune Modulating Nanosystems
Abstract: The adaptive immune system has evolved as a means for efficiently mounting and maintaining defense against invading pathogens. Conversely, there are various mechanisms to prevent immune attack of self-antigens to maintain tolerance to the host. Such mechanisms include the presence of specialized regulatory T cells (Tregs) that suppress effector lymphocyte function, and tolerogenic dendritic cells (tDCs) that promote the development of Tregs. When these regulatory mechanisms are compromised autoimmunity ensues, resulting in chronic inflammation and various secondary complications. Conventional treatments for autoimmune disorders range from small-molecule general immune suppressants to biologic drugs targeting pathways of immune activation, but nanoparticle-based approaches remain largely unexplored. By targeting modulating agents to key pathways of the adaptive immune system, we investigated several approaches to inducing immune tolerance using biodegradable nanoparticles. We demonstrate that direct delivery of suppressive cytokine combination TGF-β and IL-2 to helper T cells through CD4 receptor targeted nanoparticles induces expansion and stability of polyclonal Tregs in-vitro and in-vivo. Upstream from Treg induction, DCs represent a major subset of antigen-presenting cells that can be tuned to generate antigen-specific T and B cell responses. By targeting DC endocytic pathways using nanoparticles coated with anti-DEC205 antibodies, we co-delivered antigen with immunosuppressive drugs to induce a tolerogenic phenotype. The tolerized DCs concurrently process and present the delivered antigen. Downstream effects of the treatment included antigen-specific Treg expansion, suppression of antigen-specific effector T and B cell proliferation, and inhibition of antibody titers. Furthermore, our DC-targeting nanoparticle platform facilitates co-encapsulation of suppressive drugs that synergize when acting within the same DC. We show that mycophenolic acid and rapamycin, when codelivered to DC via nanoparticles, potently suppress T cell activation in mixed lymphocyte reactions and prevent the onset of type 1 diabetes in a mouse model. Together, our findings highlight the utility of nanoparticles for treating autoimmunity by generating immune tolerance.