Alan L. Schneyer

Alan L. Schneyer

Adjunct Professor, Department of Biology, University of Massachusetts

Ph.D.: University of Miami
Postdoc: Albany Medical College

Research Interests

Members of the TGFβ family are critical regulators of cell growth, survival and function and have important roles in development and tissue fate determination. My lab focuses on the activin/myostatin/GDF11 branch of the TGFβ family tree, and this group of hormones is regulated by the extracellular anagonists follistatin (FST) and follistatin like-3 (FSTL3). These antagonists are structurally and biochemically related, bind ligand irreversibly, and regulate the bioactivity of activin, myostatin, and GDF11 in numerous tissues. Research in my lab is concentrated on the roles of these growth factors and their antagonists in two areas, metabolism and reproduction.

To examine the in vivo actions of FSTL3 and FST in adults, we created mice in which the FSTL3 gene was inactivated and found that these mice develop a suite of metabolic phenotypes, including enlarged pancreatic islets, β-cell hyperplasia, improved insulin sensitivity and glucose tolerance, reduced visceral fat, and fatty liver. We have also created mice in which the FST gene was modified so that the circulating FST isoform, FST315 is not synthesized while the FST288 isoform important for development is made normally. These mice are subfertile with some metabolic phenotypes. The double mutant mouse is different still, with insulin resistance and increased adiposity. Taken together, these two mouse models reinforce the concept that regulation of activin, myostatin, and/or GDF11 by FSTL3 and/or FST is critical for normal glucose metabolism in adults.

We are also interested in the roles of these growth factors and antagonists on pancreatic islet composition and β-cell expansion since the FSTL3 KO mouse had larger islets with more β-cells than WT mice. Our current research explores the source of these new β-cells with the hope that understanding regulation of β-cell expansion in these mice could lead to new treatments for diabetes.

The FST mutant mice (FST288-only) also have an interesting reproductive phenotype that is similar to human Premature Ovarian Failure (POF) also known as Primary Ovarian Insufficiency (POI). FST288-only females usually stop breeding between 6-9 months due to a deficit of primordial follicles. We identified the source of this defect as the pool of primordial follicles, which is initially larger but becomes depleted faster. The cause of the larger initial primordial follicle pool and its greater instability are currently under investigation.

Current activities in the lab are concentrated on deciphering the biochemical, molecular and genetic mechanisms whereby each of these phenotypes are manifested, as well as to further characterize the precise nature and onset of each phenotype to determine their interrelattedness. The results of these studies will lead to new understanding of the role FSTL3 and FST, as well as the TGFβ superfamily ligands they regulate, in maintaining normal glucose meetabolism and reproduction in adults and also provide the basis for development of new pharmaceutical approaches for treating diabetes, insulin resistance and infertility.