Donna Davidson

Award

Bio

Donna graduated from Worcester Polytechnic Institute (WPI) in 2007 with a Bachelor Photo of Donna Davidsonof Science in Biology and Biotechnology. In the summer of 2006, Donna had the opportunity to participate in the Summer Scholars Program at the University of Rochester and was able to extend her laboratory experience there to gather data for her senior research project at WPI, for which she was awarded the Provost Award for Outstanding Major Qualifying Project in Biology and Biotechnology. In the fall of 2007 she joined the Department of Microbiology and Immunology at the University of Rochester and subsequently joined the lab of Dr. Sanjay Maggirwar. During her time here she has had the opportunity to present her work at several international conferences, winning travel awards in both 2009 and 2010 from the Society on NeuroImmune Pharmacology, and is an active member in the professional societies of Women in Neurovirology as well as the Society on NeuroImmune Pharmacology. In the fall of 2009 Donna earned her Master of Science degree and is currently working on her thesis project.

Research Description

Human immunodeficiency virus type 1 (HIV-1) enters the central nervous system (CNS) in the early stages of infection, and can lead to the development of cognitive, motor, or behavioral deficiencies, referred to as HIV-1-associated neurocognitive disorders (HAND). Infiltration of the CNS by activated or infected monocytes/macrophage is believed to be one of the largest contributing factors in the pathogenesis of HAND, due to the induction of an excessive inflammatory state that causes neuronal damage and eventual death. Currently there is a shortage of therapies to address this aspect of HIV-1 infection; however, it is not due to a lack of need, but rather a lack of complete understanding of the mechanisms employed by the virus to enter the CNS and induce a neurotoxic, inflammatory environment.

Previous work from the laboratory of Dr. Maggirwar reported that HIV-1 infected, cognitively impaired individuals have elevated levels of soluble CD40L (CD40L) in their plasma and cerebrospinal fluid as compared to HIV-1 infected individuals that are not cognitively impaired. It is widely believed that the blood brain barrier (BBB) is frequently compromised in HAND, while sCD40L is thought to regulate BBB permeability in other inflammatory disorders of the CNS (e.g. cerebral malaria), thereby suggesting a link between sCD40L and the pathogenesis of HAND. Consistent with this notion, Donna is currently investigating the role of sCD40L in the disruption of the BBB, thus allowing infiltration of the CNS by activated/infected monocytes. Her work focuses on the ability of the HIV-1 transactivator of transcription (Tat) to induce platelet activation and subsequent release of sCD40L in vivo, where she can then measure the effect that this has on BBB permeability using the fluorescent tracer sodium fluorescein. Donna is also investigating the inflammatory aspects of sCD40L by measuring the upregulation of inflammatory cytokines and chemokines within murine brain tissue in response to either recombinant sCD40L, or Tat in the presence or absence of CD40L. Exploring the mechanisms by which the BBB becomes compromised during HIV-1 infection has the potential to reveal novel therapeutic targets, thereby aiding in the development of adjunct therapies for the management of HAND, which are currently lacking.

Articles Published

  1. Davidson, DC, Hirschman, M, Spinelli, SL, Morrell, CN, Schifitto, G, Phipps, RP, and Maggirwar, SB. Antiplatelet activity of valproic acid contributes to decreased soluble CD40 ligand production in Human Immunodeficiency Virus type 1 infected individuals. J Immunol. 2011 Jan 1;186(1):584-91. Epub 2010 Nov 29.
  2. Davidson, DC, Schifitto, G, and Maggirwar, SB. Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus infected individuals. Manuscript in preparation.
  3. Refaai, MA, Carter, J, Davidson, DC, Masel, E, Smith, BH, Henrichs, KF, Pollock, S, Spinelli, SL, Phipps, RP, Francis, CW, and Blumberg, N. Platelet activation following in vitro exposure to anti-ABO antibodies. Manuscript in preparation.

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