The University of Toledo

Cynthia M. Smas, D.Sc.

Cynthia Smas, D.Sc. Associate Professor of Biochemistry and Cancer Biology cynthia.smas@utoledo.edu

RESEARCH INTERESTS:

Obesity is now at epidemic proportions and is closely linked to co-morbidities including heart disease and diabetes. There is no question that this is a significant health problem in this country. In order to better understand and treat obesity we are studying adipogenesis and preadipocyte/adipocyte function.     We are identifying novel gene products that show adipose tissue specific expression patterns, hormonal regulation, and protein sequence elements indicative of important roles in preadipocyte or adipocyte function; we are characterizing their function in the pathogenesis of obesity. A particular interest here is novel secreted products of adipocytes, termed adipokines, in that their actions likely impact systemic physiology and as such have the potential to act as therapeutic targets in the fight against obesity and its co-morbidities.  We are also interested in the proteins comprise and control the function of the adipocyte lipid droplet; we have published two manuscripts in the last few years on one such protein, Fat Specific Protein 27 (FSP27) also known as CIDE-C (Kim, J.Y., Lui, K., Zhou, S., Tillison, K., Wu, Y., and Smas, C.M. “Assessment of Fat Specific Protein 27 (FSP27) in the Adipocyte Lineage Suggests a Dual Role for FSP27 in Adipocyte Metabolism and Cell Death”.  Am. J. Physiol. Endocrinol. Metab., 294:E654-E667, 2008 and    Liu, K., Zhou, S., Kim, JY, Tillison, K., Majors, D., Rearick, D., Lee, JH, Fernandez-Boyanapalli, R.F., Barricklow, K., Houston, M.S., and Smas, C.M. “Functional Analysis of FSP27 Protein Regions for Lipid Droplet Localization, Caspase-Dependent Apoptosis, and Dimerization with CIDEA”.  Am. J. Physiol. Endocrinol. Metab., 297:E1395-E13413, 2009. 

To better study adipocytes, we have also invested effort in generation of new cell culture models. One of these ScAP23, was published in 2007  (Kim, J.Y., Wu, Y., and Smas, C.M. “Characterization of ScAP-23, a New Cell Line from Murine Subcutaneous Adipose Tissue, Identifies Genes for the Molecular Definition of Preadipocytes”. Physiol. Genomics. 31:328-42, 2007).  A manuscript on another novel cell culture model we developed, mBAP-9 (a model of brown adipocytes) is currently in preparation for publication (Kim, J.Y., Wu, Y., and Smas, C.M. “Novel Adipocyte-Enriched Genes Revealed by Characterization of mBAP-9, a New in vitro Brown Adipogenesis Model”).

In addition, we aim to better understand the preadipocyte and the early stages of adipocyte lineage commitment, much of which still remains to be elucidated.  In contrast to fat cells, studies of preadipocytes area largely un-mined research area.  By better understanding this cell type we can potentially target obesity before its formation, at the preadipocyte stage.

Member of the mentoring faculty for the Biomedical Sciences Graduate Program (Cancer Biology track and Cardiovascular & Metabolic Disease track). 

Development of New Adiposgenesis Models:  ScAP23 are a new preadipocyte cell line developed in our laboratory from murine white adipose tissue.  Upon adipogenic induction, ScAP23 preadipocytes differentiate to functional fat cells as evidenced here by accumulation of lipid droplets.  Lipid droplets appear refractile in the live image in the left panel and are stained with Oil Red O in the right panel.  The development and characterization of this novel preadipocyte model for the in vitro study of adipogenesis and adipocyte function was published in AJP (Endocrinology and Metabolism).

EDUCATION: 

1980	B.A. Biology, Boston University, Boston, MA
1985	M.S. Biological Sciences, University of Massachusetts, Lowell, MA - Thesis title: “Genome Organization of Bovine Herpes Virus”
1994	D.Sc. Nutritional Biochemistry, Harvard University, School of Public Health - Division of Biological Sciences, Boston, MA - Dissertation title: “Studies on Pref-1, a Novel Inhibitory Regulator of Adipogenesis"

ACADEMIC APPOINTMENTS: 

2008 - present	Associate Professor (tenure-track), Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, OH (tenure granted 2011)
2007 - 2009	Cancer Biology Track Vice-Director, Cancer Biology Graduate Program Track, University of Toledo College of Medicine, Toledo, OH
2003 - present	Adjunct Faculty, Department of Nutrition Sciences, Bowling Green State University,  Bowling Green, OH (Volunteer)
2000 - 2007	Assistant Professor (tenure-track), Department of Biochemistry and Cancer Biology (formerly Department of Biochemistry and Molecular Biology), University of Toledo College of Medicine (formerly Medical College of Ohio), Toledo, OH

       
BIBLIOGRAPHY (Published works)

Articles published in scientific journals - peer reviewed primary research articles

Yang, X., Heckmann, B.L., Zhang, X., Smas, C.M., and Liu, J. (2012) Distinctive mechanisms are involved in regulation of ATGL-mediated adipocyte lipolysis by lipid droplet coat proteins. J. Molec. Endocrinol., in press.

Ren, G. Kim, J-Y., and Smas, C.M. (2012) Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am. J. Physiol. Endocrinol. Metab. 303:E334-E351.
 
Lee, J.H., Zhou, S., and Smas, C.M. Identification of RANBP16 and RANBP17 as Novel Interaction Partners for the bHLH Transcription Factor E12.  J. Cell. Biochem, 11:195-206, 2010.

Wang, Y, Zhao, L., Smas, C.M., and Sul, H.S. Pref-1 Interacts with Fibronectin to Inhibit Adipocyte Differentiation. Mol. Cell. Biol., 30:3480-3492, 2010. 
        
Wu, Y., Zhou, S., and Smas, C.M. Downregulated Expression of the Secreted Glycoprotein Follistatin-like 1 (Fstl1) is a Robust Hallmark of Preadipocyte to Adipocyte  Conversion.  Mech. Dev., 127:183-202, 2010. 

Charkrabarti, P., English, T., Shi, J., Smas, C.M., and Kandror, K. Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage.  Diabetes, 59:775-781, 2010.

Liu, K., Zhou, S., Kim, JY, Tillison, K., Majors, D., Rearick, D., Lee, JH, Fernandez-Boyanapalli, R.F., Barricklow, K., Houston, M.S., and Smas, C.M. Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.  Am. J. Physiol. Endocrinol. Metab., 297:E1395-E13413, 2009. 

Wu, Y., and Smas, C.M. Expression and regulation of transcript for the novel transmembrane protein Tmem182 in the adipocyte and muscle lineage.  BMC Res. Notes 1: 85, 2008.

Wu, Y., Kim, J.Y., Zhou, S., and Smas, C.M. Differential screening identifies transcripts with depot-dependent expression in white adipose tissues. BMC Genomics, 9:397, 2008.  

Wu, Y., and Smas, C.M. Wdnm1-like, a new adipokine with a role in MMP-2 activation.  Am. J. Physiol. Endocrinol. Metab., 295:E205-15, 2008.

Kim, J.Y., Lui, K., Zhou, S., Tillison, K., Wu, Y., and Smas, C.M. Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death..  Am. J. Physiol. Endocrinol. Metab., 294:E654-E667, 2008.

Kim, J.Y., Wu, Y., and Smas, C.M. Characterization of ScAP-23, a new cell line from murine subcutaneous adipose tissue, identifies genes for the molecular definition of preadipocytes. Physiol. Genomics. 31:328-42, 2007.

Kim, J.Y., Tillison, K.S., Zhou, S. Lee, J.H., and Smas, C.M. Differentiation-dependent expression of Adhfe1 in adipogenesis.  Arch. Biochem. Biophys. 464:100-111, 2007.

Kim, J.Y., Tillison, K.S., Zhou. S. Wu, Y., and Smas, C.M. The major facilitator superfamily member Slc37a2 is a novel macrophage- specific gene selectively expressed in obese white adipose tissue.  Am. J. Physiol. Endocrinol. Metab., 293: E110—E120, 2007.

Kim, J.Y., Tillison, K., Lee, J.H., Rearick, D.A., and Smas, C.M. The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma.  American J. Phys. Endo. Metabol., 291:E115-E127, 2006. 

Kim, J.Y., Tillison, K. and Smas, C.M.  Cloning, expression, and differentiation-dependent regulation of SMAF1 in adipogenesis.  Biochem. Biophys. Res. Commun. 326:36-44, 2005.

Moon#, Y.S., Smas#, C. M., Lee#, K., Villena, J. A., Kim. K.H., Yun E.J., and Sul, H.S. Mice Lacking Paternally Expressed Pref-1/Dlk1 Display Growth Retardation and Accelerated Adiposity. Mol. Cell. Biol. 22:5585-92, 2002. (#: equal first co-authorship)

Smas, C.M., Chen, L., Zhao, L., Latasa, M.J., and Sul, H.S. Transcriptional Repression of Preadipocyte Factor-1 by Glucocorticoids Promotes 3T3-L1 Adipocyte Differentiation.  J. Biol. Chem. 274:12632-12641, 1999.
    
Smas, C.M., Kachinskas, D., Liu, C., Xie, X., Dircks, L.K., and Sul, H.S. Transcriptional Control of the Pref-1 Gene in 3T3-L1 Adipocyte Differentiation.  Sequence Requirement for Differentiation-Dependent Suppression.  J. Biol. Chem. 273:31751-31758, 1998.

Smas, C.M., Chen, L., and Sul, H.S. Cleavage of Membrane-Associated Pref-1 Generates a Soluble Inhibitor of Adipocyte Differentiation.  Mol. Cell. Biol. 17:977-988, 1997.
           
Smas, C.M., Green, D., and Sul, H.S. Structural Characterization and Alternate Splicing of the Gene Encoding the Preadipocyte EGF-like Protein Pref-1.  Biochemistry 33:9257-9265, 1994.

Smas, C.M., and Sul, H.S. Pref-1, a Protein Containing EGF-like Repeats, Inhibits Adipocyte Differentiation.  Cell 73:725-734, 1993.

Adler, G.K., Smas, C.M., Fiandaca, M., Frim, D.M., and Majzoub, J.A. (1990).  Regulated Expression of the Human Corticotropin-Releasing Hormone Gene by Cyclic AMP.  Mol. Cell. Endocrinol. 70:165-174.

Gravallese, E.M., Boothby, M.R., Smas, C.M., and Glimcher, L.H. A Lipopolysaccharide-Induced DNA-binding Protein for a Class II Gene in B cells is Distinct from NF-kappa B.  Mol. Cell. Biol. 9:3184-3192, 1989.

Frim, D.M., Emanuel, R.L., Robinson, B.G., Smas, C.M., Adler, G.K., and Majzoub, J.A. Characterization and Gestational Regulation of Corticotropin-Releasing Hormone Messenger RNA in Human Placenta.  J. Clin. Invest. 82:287-292, 1988.

Adler, G.K., Smas, C.M., and Majzoub, J.A. Expression and Dexamethasone Regulation of the Human Corticotropin-Releasing Hormone Gene in a Mouse Anterior Pituitary Cell Line.  J. Biol. Chem. 263:5846-5852, 1988.


Articles published in scientific journals - peer reviewed review articles

Wolf, G., and Smas, C.M. Retinoic Acid Induces the Degradation of the Leukemogenic Protein Encoded by the Promyelocytic Leukemia Gene Fused to the Retinoic Acid Receptor Alpha Gene. Nutr. Rev. 58:211-214, 2000.

Sul, H.S., Smas, C.M., Mei, B., and Zhou, L. Function of Pref-1 as an Inhibitor of Adipocyte Differentiation. Int. J. Obes. 24 Suppl 4:S15-9, 2000.

Gregoire, F.M., Smas, C.M., and Sul, H.S. Understanding Adipocyte Differentiation. Physiol. Rev. 78:783-809, 1998.

Sul, H.S., Smas, C.M., Wang, D., Chen, L., and Fong, S. Regulation of Fat Synthesis and Adipose Differentiation. Prog. Nucleic Acid Res. and Mol. Biol. 60:317-345, 1998.

Smas, C.M., and Sul, H.S. Molecular Mechanisms of Adipocyte Differentiation and Inhibitory Action of Pref-1. Crit. Rev. Eukaryotic Gene Expr. 7:281-298, 1997.

Smas, C.M., and Sul, H.S. Characterization of Pref-1 and its Inhibitory Role in Adipocyte Differentiation. Int. J. Obesity 20:S65-S72, 1996.
   
Smas, C.M., and Sul, H.S. Control of Adipocyte Differentiation.  Biochem. J. 309:697-710, 1995.

Sul, H.S., Smas, C.M., and Moustaid, N. Positive and Negative Regulators of Adipocyte Differentiation. J. Nutr. Biochem. 4:554-562, 1993.


Chapters in books

Smas, C.M. and Sul, H. S. Control of Adipocyte Differentiation. Book chapter in: Biochemical Journal Reviews, Portland Press Ltd London, 1995, pages: 113-126.

Sul, H.S., Smas, C.M., Chen, L., Mei, B., and Zhao, L.  Pref-1, an Inhibitor of Adipogenesis.  Book chapter in: 27th Steenbock Symposium: Adipocyte Biology and Hormone Signaling, University of Wisconsin Press, WI, 2000, pages 185 - 199.

Sul, H.S., Moustaid, N., Sakamoto, K., Smas, C.M., Gekakis, N., and Jerkins, A. Nutritional and Hormonal Regulation of Genes Encoding Enzymes Involved in Fat Synthesis.  Book chapter in:  Nutrition and Gene Expression,.  Berdanier, J.L. and Hargrove, C.D. (eds.).  CRC Press, Inc., Boca Raton, FL, 1993, pages 207-226.