Rare Diseases: Models & Mechanisms Network

Basic Information

First Name
Last Name
Organization
Department
Website	https://med.uottawa.ca/bmi/people/lee-jyh-yeuan-eric

Contact Information

Email	jyh-yeuan.lee@uottawa.ca
Phone	+1-613-562-5800 x8308

About My Research

The primary objective of my research is to study the roles and regulations of the molecular lipid-transporting machinery that regulates cholesterol metabolism and lipid homeostasis. By using cellular, biochemical and biophysical model systems, we aim to uncover the molecular and atomic details that underlie the biological processes and mechanisms leading to health conditions, particularly cardio-metabolic disorders and neurodegeneration. The research outcomes will ultimately enable new-generation pharmaceutical discovery and medicinal intervention for these health conditions. Currently, we have focused on the membrane-embedded molecular machinery responsible for cholesterol and phospholipid trafficking on cellular membranes, including ATP-binding cassette (ABC) proteins and Type-IV P-type (P4) ATPases. The ongoing projects that are ssociated with known diseases include: ABCG5/G8 to sitosterolemia and dyslipidemia, ABCA1 to Tangier disease and dyslipidemia, and P4-ATPases to diabetics and Alzheimer's disease. We utilize structural biology approaches to study the mechanism of biological molecules and use yeast cells for protein engineering and for developing phenotypical and functional models of diseases.

Human Cell Models Research Focus

Human genes are our primary targets in our research program to establish biochemical and biophysical models and to study the molecular mechanism of the proteins encoded by these genes. We employ large-scale purification of recombinant human membrane proteins using yeast or insect expression systems, develop in vitro functional assays, and establish structure-function studies of these membrane proteins. Onsite or through collaboration, we also use mammalian cell models and transgenic mouse models to study disease variants of these proteins.

Genes
Terms

Gene ID	Symbol	Name	Tier
57194	ATP10A	ATPase phospholipid transporting 10A (putative)	TIER2
19	ABCA1	ATP binding cassette subfamily A member 1	TIER2
64137	ABCG4	ATP binding cassette subfamily G member 4	TIER2
64240	ABCG5	ATP binding cassette subfamily G member 5	TIER1
57205	ATP10D	ATPase phospholipid transporting 10D (putative)	TIER2
9619	ABCG1	ATP binding cassette subfamily G member 1	TIER1
64241	ABCG8	ATP binding cassette subfamily G member 8	TIER1

Term	Name	Aspect	Overlap	Size

Budding Yeast Research Focus

The yeast orthologs of human ATP8A, ATP10A and ATP10D are Drs2, Dnf1 and Dnf2. So far, studies of P4-ATPase phospholipid transporters have been primarily established with yeast proteins. In addition to human genes, we are simultaneously using yeast genes as model systems to study their biochemical properties and molecular mechanisms.

Genes
Terms

Gene ID	Symbol	Name	Tier
851207	DRS2	aminophospholipid-translocating P4-type ATPase DRS2	TIER1
856913	DNF1	aminophospholipid-translocating P4-type ATPase DNF1	TIER1
851667	DNF2	aminophospholipid-translocating P4-type ATPase DNF2	TIER2
854763	NEO1	aminophospholipid-translocating P4-type ATPase NEO1	TIER2
850456	CDC50	aminophospholipid translocase regulatory protein CDC50	TIER1

Term	Name	Aspect	Overlap	Size

Publications