Raymond Pasek

Hometown:
Buffalo, NY

Education:
BS Biochemical Pharmacology, State University of New York at Buffalo
Ph.D Cell Biology, University of Alabama at Birmingham

Research Description

During pregnancy, maternal β-cells undergo compensatory changes including increases in β-cell mass, glucose sensitivity, and glucose-stimulated insulin secretion (GSIS). Failure of these adaptations results in gestational diabetes. Studies from our lab revealed that Connective tissue growth factor (Ctgf) is critical for β-cell development. During development, Ctgf is expressed in pancreatic ducts, vasculature, and β-cells. In the absence of Ctgf, fewer β-cells are specified and β-cell proliferation is reduced, resulting in lower β-cell mass at birth. Ctgf expression in β-cells is silenced soon after birth. Here we show that pregnant mice with global Ctgf haploinsufficiency (CtgfLacZ/+) have impaired maternal β-cell proliferation; no difference was observed in virgin females. Conditional inactivation of Ctgf in endocrine cells (CtgfEndo) did not impair β-cell proliferation during pregnancy. However, CtgfEndo mice develop gestational diabetes, due to reduced GSIS. This is the first report of a role for Ctgf in β-cell function. The impact of Ctgf on both β-cell proliferation and function suggests that Ctgf could be used to expand functional β-cell mass in humans. Indeed, recombinant human Ctgf (rhCTGF) stimulates human β-cell proliferation ex vivo. We generated biodegradable poly(lactic-co-glycolic acid) microspheres containing rhCTGF, These microspheres are cotransplanted with adult human cadaver donor islets under the kidney capsule of immunocompromised mice. Islet grafts are analyzed for β-cell proliferation, function and survival. Taken together, our studies reveal novel aspects of β-cell compensation during pregnancy and have developed a novel potential therapeutic for human β-cell expansion.

Honors and Awards

  1. Recipient of American Diabetes Association Young Investigator Travel Grant Award, June 2016
  2. Recipient of Joint Meeting of The Islet Study Group and Beta Cell Workshop Travel Grant Award, May 2015
  3. Awarded an American Heart Association Postdoctoral Fellowship grant (14POST20380262), from July 2014 to present
  4. Granted an appointment on the Molecular Endocrinology Training Grant NIH grant (T32DK07563), from January 2013 to June 2014.

Publications

Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse.

Pasek RC, Malarkey E, Berbari NF, Sharma N, Kesterson RA, Tres LL, Kierszenbaum AL, Yoder BK.

Dev Biol. 2016 Apr 15;412(2):208-18. doi: 10.1016/j.ydbio.2016.01.042. Epub 2016 Mar 3.

Macrophages are essential for CTGF-mediated adult β-cell proliferation after injury.

Riley KG, Pasek RC, Maulis MF, Dunn JC, Bolus WR, Kendall PL, Hasty AH, Gannon M.

Mol Metab. 2015 May 19;4(8):584-91. doi: 10.1016/j.molmet.2015.05.002. eCollection 2015 Aug.

Connective tissue growth factor modulates adult β-cell maturity and proliferation to promote β-cell regeneration in mice.

Riley KG, Pasek RC, Maulis MF, Peek J, Thorel F, Brigstock DR, Herrera PL, Gannon M.

Diabetes. 2015 Apr;64(4):1284-98. doi: 10.2337/db14-1195. Epub 2014 Nov 12.

Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways.

Gilley SK, Stenbit AE, Pasek RC, Sas KM, Steele SL, Amria M, Bunni MA, Estell KP, Schwiebert LM, Flume P, Gooz M, Haycraft CJ, Yoder BK, Miller C, Pavlik JA, Turner GA, Sisson JH, Bell PD.

Am J Physiol Lung Cell Mol Physiol. 2014 Jan;306(2):L162-9. doi: 10.1152/ajplung.00095.2013. Epub 2013 Nov 8.

Advancements and challenges in generating accurate animal models of gestational diabetes mellitus.

Pasek RC, Gannon M.

Am J Physiol Endocrinol Metab. 2013 Dec 1;305(11):E1327-38. doi: 10.1152/ajpendo.00425.2013. Epub 2013 Oct 1. Review.

Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice.

Berbari NF, Pasek RC, Malarkey EB, Yazdi SM, McNair AD, Lewis WR, Nagy TR, Kesterson RA, Yoder BK.

Proc Natl Acad Sci U S A. 2013 May 7;110(19):7796-801. doi: 10.1073/pnas.1210192110. Epub 2013 Apr

Quantitative peptidomics of Purkinje cell degeneration mice.

Berezniuk I, Sironi JJ, Wardman J, Pasek RC, Berbari NF, Yoder BK, Fricker LD.

PLoS One. 2013 Apr 8;8(4):e60981. doi: 10.1371/journal.pone.0060981. Print 2013.

Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis.

Pasek RC, Berbari NF, Lewis WR, Kesterson RA, Yoder BK.

Cilia. 2012 Nov 1;1(1):20. doi: 10.1186/2046-2530-1-20.

LT-IIc, a new member of the type II heat-labile enterotoxin family encoded by an Escherichia coli strain obtained from a nonmammalian host.

Nawar HF, King-Lyons ND, Hu JC, Pasek RC, Connell TD.

Infect Immun. 2010 Nov;78(11):4705-13. doi: 10.1128/IAI.00730-10. Epub 2010 Aug 16.

Utilization of conditional alleles to study the role of the primary cilium in obesity.

Kesterson RA, Berbari NF, Pasek RC, Yoder BK.

Methods Cell Biol. 2009;94:163-79. doi: 10.1016/S0091-679X(08)94008-5. Epub 2009 Dec 23. Review.