# THE ROLE OF PHOSPHOLIPOGENESIS IN DIABETIC PERIPHERAL ARTERIAL DISEASE

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $92,919

## Abstract

Abstract
Application Summary: The proposal entails a three-year training program focused on preparing the principle
investigator (PI) for an independent career as a surgeon-scientist in the field of diabetic peripheral arterial
disease. The PI previously earned a PhD in Pharmacology and obtained additional training in translational
cardiovascular research. He is currently an Assistant Professor in the Department of Surgery, Section of
Vascular Surgery, at Washington University. The project and career development plan aim to impart skills and
knowledge required for the applicant to achieve his long-term goals of contributing insights into the role of
phospholipid synthesis (phospholipogenesis) and endothelial cell (EC) lipidomics in peripheral arterial
pathology in the setting of diabetes. The immediate training objectives of the PI are to master critical
experimental techniques, complete coursework that will expand his understanding of lipid metabolism and drug
development, develop administrative skills necessary for later autonomy, and produce a body of scientific work
that will facilitate funding as an independent surgeon-scientist. Dr. Clay Semenkovich, Chief of Endocrinology,
Metabolism, and Lipid Research at Washington University, and a carefully selected panel of career
development committee members, will mentor and provide the resources necessary to achieve his goals for
transition to independence.
Project Summary: Diabetic peripheral arterial disease (PAD) is a highly prevalent disease process with
significant morbidity that leads to stubbornly high rates of wounds, infections, and major extremity amputations.
Previous studies demonstrate that in the setting of diabetes there is decreased arterial collateral development
and significantly altered tissue-specific phospholipid expression (phospholipogenesis). But due to lake of
animal models, little is known regarding the role of phospholipogenesis in the vascular endothelium in the
setting of diabetes. The PI has observed that choline-ethanolamine phosphotransferase-1 (CEPT1; the
terminal enzyme required for the synthesis of the majority of mammalian phospholipids) has altered expression
in the peripheral arterial intima in the setting of diabetes and advanced atherosclerotic disease. CEPT1
expression can also be manipulated in ECs with sulfhydryl reducing pharmacological agents. Pilot human
studies also demonstrate that specific CEPT1-generated, arachidonic acid (AA)-containing, plasmenyl-
phosphatidylethanolamine (pPE) have altered expression in the peripheral arterial intima of diabetic patients.
The data suggests that CEPT1-mediated phospholipogenesis is dependent on specific disease states (i.e.
diabetes and PAD) and can be potentially targeted pharmacologically. To test this hypothesis further the PI
will evaluate the role of CEPT1 and phospholipiogenesis in EC function and arteriogenesis using a novel
conditional, endothelium-specific, CEPT1 knockout mouse model. The PI will also eva...

## Key facts

- **NIH application ID:** 9849790
- **Project number:** 5K08HL132060-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Mohamed A. Zayed
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $92,919
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849790

## Citation

> US National Institutes of Health, RePORTER application 9849790, THE ROLE OF PHOSPHOLIPOGENESIS IN DIABETIC PERIPHERAL ARTERIAL DISEASE (5K08HL132060-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849790. Licensed CC0.

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