The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. has selected three promising Uniformed Services University of the Health Sciences (USU) doctoral students to receive fellowships for the 2012-13 academic year. The program, established in 1988, includes two Henry M. Jackson Fellowships and one Val G. Hemming Fellowship. Each fellow receives a stipend and travel support.
Suman Paul, a sixth-year graduate student in the Emerging Infectious Diseases program, was awarded the Val G. Hemming Fellowship. Paul works in the laboratory of Dr. Brian Schaefer, focusing on T cell mediated immune response that control pathogen infection.
Paul is investigating the mechanism of T cell receptor (TCR) signaling. Upon recognizing a foreign antigen, an "activated" TCR initiates a signal transduction cascade that results in the production of effector T cells in sufficient quantities to mount an effective immune response and eliminate specific pathogens or pathogen infected cells. A key mediator in this cascade is the protein Bcl10, which facilitates the activation of the transcription factor NF-KB, which induces effector T cell activation and proliferation. Paul found that Bcl10 is specifically degraded following TCR activation via a newly identified process called selective autophagy, resulting in an attenuation of the TCR-mediated signal transduction. This finding may lead to insights into how to clinically modulate unrestricted T cell activation that results in autoimmune disease and neoplasms, and graft rejection after organ transplant. Moreover, the research may contribute to an understanding of a new molecular mechanism by which a receptor precisely controls the extent of activation of a target transcription factor in diverse signaling pathways.
Darwin Omar Larco, recipient of a Henry M. Jackson Fellowship, is a fifth-year student completing his thesis project in Dr. T. John Wu's laboratory in the Molecular and Cell Biology program at USU. Larco's project focuses on understanding the function of the gonadotropin-releasing hormone metabolite, GnRH-(1-5), and its role in development and regulation of the reproductive system.
In particular, Larco is working to elucidate the signaling mechanism of GnRH-(1-5) to modulate the migration of GnRH-secreting neurons during development. GnRH is produced in the hypothalamus and is a primary regulator of reproductive function. GnRH-(1-5) is a five amino acid cleavage product of the decapeptide GnRH that has been found to possess biological activity distinct from GnRH. Larco's research has led to the identification of an as yet uncharacterized receptor believed to mediate the function of GnRH-(1-5). Larco hopes that his further research will identify some of the effectors in the downstream signaling pathway of GnRH-(1-5), which may lead to a better understanding of developmental defects of the GnRH neuroendocrine system, where the onset of puberty and fertility are impaired.
Sandra Bixler, a fifth-year student in the Emerging Infectious Diseases program, also received a Henry M. Jackson Fellowship. Working in the laboratory of Dr. Joseph Mattapallil, Bixler's thesis project uses simian immunodeficiency virus (SIV) as a model for studying the host response to HIV infection.
Bixler is exploring the mechanism behind the failure of a specific class of immune cells (called Th17 cells) to repopulate during chronic HIV infection. Th17 cells are responsible for maintaining mucosal defense against fungi and extracellular bacteria; the loss of these helper T cells in HIV infected individuals likely contributes to immune activation and disease progression. Bixler found that SIV infection negatively regulates the expression of IL-17, a critical cytokine produced by Th17 cells. She is working to ascertain if Th17 cell induction can be rescued by suppression or activation of specific targets in the pathway responsible for IL-17 expression. Bixler's research may lead to improved prognosis in HIV-infected individuals, by finding methods to restore the repopulation of Th17 cells.
Patient-derived organoids: Transforming cancer research and personalized medicine