PROJECT SUMMARY/ABSTRACT
Defects in lipid metabolism are associated with neurological diseases and mood disorders, but
bioenergetics and regulation of lipid metabolism in the brain is not well defined. The brain is the most lipid-rich
tissue in mammals other than adipose with a unique profile of lipids necessary for proper nervous system
structure and function. However, how the brain uses lipids for energy and responds to dietary conditions that
impact available lipids is grossly understudied. Historically, there has been little consideration for a) the
existence, capacity, and relevance of fatty acid oxidation (FAO) in the brain in comparison to more prominent
sources of energy such as glucose (and ketones during fasting and starvation) nor b) how the brain senses
and adapts to changes in availability of lipids. Throughout my predoctoral training, I have already determined
(Aim 1a) that the mammalian brain normally oxidizes long chain fatty acids in vivo to a greater extent than
previously considered using a pan-brain-specific conditional mouse model incapable of FAO (manuscript in re-
review in MCB) and (Aim 1b) identified that expression of ethanolamine phosphate phospholyase (Etnppl)
(funded by F31, manuscript in prep), which has links to schizophrenia and bipolar disorder in humans, is
upregulated by dietary fasting specifically in astrocytes from Ribo-Tag mice using translating ribosomal affinity
purification. The contributions of ETNPPL to the brain metabolome were evaluated using constitutive ETNPPL
knockout mice (ETNPPL-/-). Under the F99 phase, I will study (Aim 2a) how perturbations in hepatic FAO
(supplies brain ketones), using mice with FAO deletion in both brain and liver, impacts FAO bioenergetics in
brain and (Aim 2b) continue studying how the brain responds to metabolic cues by further characterizing
ETNPPL in the brain using adeno-associated virus-injected ETNPPL overexpressed mice. In preparation for
postdoctoral studies, I will expand my knowledge in neuro-HIV in a neuro-HIV seminar series, neuro-HIV
course, and other didactic training opportunities offered at Johns Hopkins in the F99 phase. Aims 1 was and
Aim 2 will be conducted in the laboratory of Michael Wolfgang, Ph.D. at Johns Hopkins School of Medicine
during my graduate studies in the Biochemistry, Cellular and Molecular Biology Ph.D. Program. For the K00
phase, (Aim 3) I am pursuing postdoctoral training that will expand my current knowledge in lipid
neurometabolism in the context of an infectious disease with neuropathological manifestations. I have a
particular interest in the impact on brain lipid metabolism by HIV infection. This interest is based on high
indices of cognitive impairment and dementia in HIV infected patients (collectively known as HAND), the brain
being a reservoir for HIV, and antiretroviral drugs used long-term to treat HIV having metabolic side-effects. In
summary, these training opportunities afforded by the support of the D-SPAN award would be immensely
impactful towards my development into an innovative, independent researcher studying the intersection of
neuroscience, metabolism, and infectious disease.
