Alan Schneyer

Research Professor

Research areas are in biology and neogenesis of human and mouse pancreatic islets and beta cells; diabetes/metabolism and glucose homeostasis; metabolism and cancer; and reproduction, infertility, and premature ovarian failure. In 2014 Dr. Schneyer co-founded Fairbanks Pharmaceuticals (www.fairbankspharma.com) to pursue potential therapeutic ideas based on these research findings. The company’s research lab is located in Springfield at the Baystate Research Facility and many of the employees are UMass graduates. Fairbanks has been funded largely by Phase I and II SBIR grants. We have developed monoclonal antibodies that neutralize FSTL3 which we hypothesize will mimic the FSTL3 KO mice in producing enhanced beta cell function and transdifferentiation of new beta cells. In vitro this FSTL3 neutralizing antibody can restore function in diabetic islets and we are now testing it in vivo in mouse models of diabetes.

Current Research
My research group is focused on identification of new sources for pancreatic beta cells through regeneration and reprogramming. We have identified growth factors that control formation of new beta cells from other islet cells. Therapeutics based on this research, such as neutralizing antibodies, are being explored as treatments for both type 1 and type 2 diabetes.

Activin is a growth factor in the TGFbeta superfamily that is regulated by antagonists such as follistatin like-3 (FSTL3). FSTL3 knockout mice have enlarged islets with more beta cells and improved glucose homeostasis. We determined that these extra beta cells do not arise from proliferation, but rather appear to form via conversion of other islet cells types, mainly alpha cells. While the mechanisms for this type of conversion are a major area of research, we found that KO mice have more of these converted beta cells than wild type mice suggesting that the process is both normal and enhanced by activin. This suggests that treatments which inhibit FSTL3 or enhance activin might be useful as novel therapies for diabetes where replacement of lost beta cells is essential.

These mice also had reduced visceral fat and improved glucose homeostasis. Since obesity has been linked to cancer risk, particularly for breast cancer, possibly via alteration in hormone levels, it is also possible that FSTL3 inhibitors could be useful for reducing abdominal fat and thus, reduce cancer risk. Connections between obesity, metabolism, endocrinology and cancer are being investigated through collaborations with Drs. Jerry and Dunphy.

Learn more at www.vasci.umass.edu/research-faculty/alan-l-schneyer

Academic Background

BS University of Pennsylvania, 1976
MS University of Miami, 1980
PhD University of Miami, 1983
Postdoctoral Training: Albany Medical College, 1984-1986

Selected Publications

Li Y, Fortin J, Ongaro L, Zhou X, Boehm U, Schneyer A, Bernard DJ, Lin HY. Betaglycan (TGFBR3) Functions as an Inhibin A, but Not Inhibin B, Coreceptor in Pituitary Gonadotrope Cells in Mice. Endocrinology. 2018 Dec 1;159(12):4077-4091. doi: 10.1210/en.2018-00770.

http://dx.doi.org/10.1210/en.2018-00770.

Brown ML, Andrzejewski D, Burnside A and Schneyer AL. Activin Enhances - to -cell Transdifferentiation As A Source For -Cells In Male FSTL3 Knockout Mice. Endocrinology. 2016 Mar;157(3):1043-54. PMID: 26727106.

Andrzejewski D, Brown ML, Ungerleider N, Burnside A, Schneyer AL. Activins A and B regulate fate-determining gene expression in islet cell lines and islet cells from male mice. Endocrinology. 2015 July; 156:2440-2550. PMID: 25961841.

Brown ML, Ungerleider N, Bonomi L, Andrzejewski D, Burnside A, Schneyer A. Effects of activin A on survival, function and gene expression of pancreatic islets from non-diabetic and diabetic human donors. Islets. 2014 Nov 2;6(5-6):e1017226. doi: 10.1080/19382014.2015.1017226. PMID: 25833251. PMC4398300.

http://dx.doi.org/10.1080/19382014.2015.1017226

Ungerleider NA, Bonomi LM, Brown ML, Schneyer AL. 2013. Increased activin bioavailability enhances hepatic insulin sensitivity while inducing hepatic steatosis in male mice. Endocrinology. 154(6):2025-33.

Bonomi L, Brown M, Ungerleider N, Muse M, Matzuk MM, Schneyer A. 2012. Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity. Am J Physiol Endocrinol Metab. 303(5):E587-96.

Kimura F, Bonomi LM, Schneyer AL. 2011. Follistatin regulates germ cell nest breakdown and primordial follicle formation. Endocrinology. 152(2):697-706.