Research Interests
The Lyssenko laboratory investigates Alzheimer’s dementia (AD) and age-related macular degeneration (AMD) as sequelae of the loss of healthy lipid homeostasis. The ideas for research projects usually come from human genomics or genetics, which have linked many lipid metabolism genes and hence the genes’ protein products with the diseases of interest over the recent decades.
Currently, we focus on two members of the ATP-binding cassette transporter superfamily, subfamily A member 1 and member 7 (ABCA1 and ABCA7, respectively), a member of the P-type ATPase subfamily IV called ATPase phospholipid transporting 8B4 (ATP8B4) and the proteins encoded by the genes in the p13.2 band of chromosome 17. ABCA1, ABCA7, ATP8B4 and one or more of the proteins encoded at Chr17 p13.2 modulate the risk of AD. ABCA1 also affects the risk of AMD. ABCA1 and ABCA7 are thought to extrude lipids out of cell lipid membranes into the extracellular medium, where these lipids form small discoidal bilayer particles stabilized by apolipoproteins, such as apolipoprotein E, at the acyl chain/hydrophobic edge. ATP8B4 is thought to flip phospholipid from one leaflet of the cell lipid membrane into the other.
We address what we believe to be the most critical questions regarding the biochemical functions and pathophysiology of the lipid metabolism proteins of interest using any necessary study systems and methods. Some of the questions that we are addressing now are: how to assess ABCA7 protein levels in the cerebrum of living individuals, what is the cargo lipid of ABCA7, can ABCA7 over-expression stop and reverse AD pathogenesis in mouse models of AD, does hyperactive ABCA1 impair vision in the mouse eye, what is the expression pattern of ATP8B4 in the mouse and human brain, which gene at the Chr17 p13.2 locus modulates AD risk. The current study systems include human brain specimens, mouse models and immortalized human cells. We expect that our work will spur development of treatments for AD and AMD.
Education, Training & Credentials
- Postdoctoral, Lipid Metabolism, Cleveland Clinic/Children's Hospital of Philadelphia
PhD, Integrative Biosciences—Cell and Developmental Biology, The Pennsylvania State University, University
Park
BS, Cell and Molecular Biology and Genetics, University of Maryland–College Park
Honors
- American Heart Association Scientist Development Grant
- NIH Ruth L. Kirschstein NRSA for Individual Postdoctoral Fellows (F32)
- American Heart Association Postdoctoral Fellowship
- American Heart Association Predoctoral Fellowship, competitive renewal
- American Heart Association Predoctoral Fellowship
- The Huck Institutes of the Life Sciences Graduate Fellowship