The Effect Of Osteoprotection On Immune Reconstitution Post Bone Marrow Transplant

Specialized microenvironments have been known to strongly influence stem cell fate in hematopoiesis. The interplay between osteolineage cells, specifically the mature osteoblast, and the hematopoietic stem cell (HSC) niche have been of particular note. Recently, preliminary unpublished data obtained in the Scadden laboratory suggests the critical role of the osteoblast in regulating T cells. The goal of this project was to initially determine whether stimulating the osteoblast in the HSC niche leads to increased immune reconstitution after hematopoietic stem cell transplant (HSCT). These results indicated that while bone manipulation pre-transplant may have a positive effect on T and B lymphocyte cell recovery, bone manipulation post-transplant seems to have a suppressing effect. Additionally, stimulation of the osteoblast may have an inhibitory effect on the regeneration of GR1+ myeloid cells. Based on these results, we then sought to determine how osteoprotection pre-HSCT modifies the kinetics of graft-versus-host disease (GVHD) and impacts the regeneration of immune cells. The data from this phase of my experiment suggests a possible immediate benefit in stimulation of the osteoblast in response to GVHD prior to HSCT. The overall results from my thesis project demonstrate a promising relationship between pre-HSCT stimulation of the osteoblast and lymphocyte recovery post-HSCT. ¿

Measuring Correlation Between HIV Sequence Variation and Disease Stage of HIV-Infected Individuals

With a virus such as Human Immunodeficiency Virus (HIV) that has infected millions of people worldwide, and with many unaware that they are infected, it becomes vital to understand how the virus works and how it functions at the molecular level. Because there currently is no vaccine and no way to eradicate the virus from an infected person, any information about how the virus interacts with its host greatly increases the chances of understanding how HIV works and brings scientists one step closer to being able to combat such a destructive virus. Thousands of HIV viruses have been sequenced and are available in many online databases for public use. Attributes that are linked to each sequence include the viral load within the host and how sick the patient is currently. Being able to predict the stage of infection for someone is a valuable resource, as it could potentially aid in treatment options and proper medication use. Our approach of analyzing region-specific amino acid composition for select genes has been able to predict patient disease state up to an accuracy of 85.4%. Moreover, we output a set of classification rules based on the sequence that may prove useful for diagnosing the expected clinical outcome of the infected patient.