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The Tenure and Promotion CV: Relationships are the Common Thread. Alyssa Hasty, PhD Associate Professor Molecular Physiology and Biophysics. Tenure and Promotion Criteria. Research, Scholarship or Creative Expression Teaching Service. Tenure and Promotion Criteria.
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Alyssa Hasty, PhD
Molecular Physiology and Biophysics
The number differs by department
Names of all authors as listed sequentially on the publication:
Role of Candidate: I am the senior, corresponding author on this manuscript. The experiments were performed by Saraswathi Viswanathan, a post-doctoral fellow in my laboratory at that time. I was responsible for interpretation of the data. The manuscript was drafted by Dr. Viswanathan, and finalized and submitted by myself.
This manuscript describes our observation that very low density lipoproteins (VLDL) induce inflammatory cytokine production in macrophages. In particular, we studied the time course and dose response expression of the chemokine, macrophage inflammatory protein-1α (MIP-1α). Furthermore, we showed that the increase in inflammatory gene expression coincided with the phosphorylation of the MAPK pathway members: ERK1/2, JNK, and p38 MAPK, and was ameliorated by U0126, an inhibitor of ERK1/2. Finally, inhibition of extracellular TG hydrolysis with Orlistat resulted in the absence of intracellular TG and FFA accumulation and was accompanied by the amelioration of ERK1/2 phosphorylation and MIP-1α gene expression. These results are important because hypertriglyceridemia is a hallmark characteristic of obesity-related dyslipidemia, and macrophages play a critical role in both atherosclerotic lesion formation and insulin resistance. Thus, we concluded that elevations in TG-rich VLDL may contribute to the pathogenesis of obesity by increasing inflammation in macrophages. These studies helped lay the foundation for both my American Diabetes Association grant to study MIP-1α in atherosclerosis and insulin resistance, as well as my NIH R01 to study the role of fatty acids in macrophage accumulation in adipose tissue.
These data have important implications to the pathogenesis of diet-induced obesity in humans, even when plasma lipid abnormalities are not present. This publication was also instrumental in helping me obtain my R01. In addition, they brought me recognition in the field of macrophage infiltration into AT, and I was subsequently asked to write two review articles on the topic.
Development of this mouse model has led to a collaborative effort between my laboratory and Drs. Judy Aschner, Jeff Reese, and BC Paria to study the impact of maternal obesity on the cardiovascular outcomes in the offspring. We have obtained P&F funding for this project and are currently obtaining preliminary data in order to submit a multi-PI NIH R01 application next year. In addition, Dr. Coenen and I will be writing a review article on mouse models of the metabolic syndrome to be submitted to the journal Disease Models and Mechanisms this Fall.
This publication has lead to the development of 4 new collaborations for my lab. (1) We are collaborating with Dr. Charles Wilkins at the University of Arkansas to assess phospholipid levels in tissues from these mice, and have a manuscript in submission. (2) We are collaborating with Dr. Alan Tall at Columbia University to determine the effect of fish oil on the phagocytic index of arterial macrophages. (3) We are collaborating with Dr. Edward Fisher at New York University to determine whether fish oil impacts apoB aggregation in liver. (4) We are collaborating with Dr. Naima Moustaid-Moussa at the University of Tennessee Knoxville to determine whether fish oil impacts adipose tissue expression of genes involved in the renin angiotensin system.
University of Pennsylvania School of Medicine
Theodore Mazzone, MD
Professor of Medicine, University of Illinois at Chicago
Chief, Section of Diabetes and Metabolism MC 797
Alan Daugherty, PhD, D.Sc.
Professor of Medicine and PhysiologyGill Foundation Chair in Preventive CardiologyDirector, Cardiovascular Research Center
Jay Heinecke, PhD
Professor of MedicineDivision of Metabolism, Endocrinology and Nutrition
University of Washington School of Medicine
Murray Huff, PhD
Professor, Departments of Medicine and Biochemistry
University of Western Ontario
Ira Tabas, MD. PhD
Professor of Medicine and Anatomy & Cell Biology, Department of MedicineColumbia University
Only 4 of 17 were from people I did not know
1 book chapter
17 were from my lab