Obesity prevalence and its complications of diabetes mellitus and cardiovascular disease are increasing. Understanding the mechanisms controlling adipose tissue development are critical if effective strategies are to be developed for prevention and treatment. We are investigating the signaling pathways used by Insulin-like growth factor-I to mediate adipogenesis, which is the proliferation and differentiation of adipocyte precusor cells and leads to adipose tissue expansion and obesity.

We have been investigating the signaling pathways controlling adipogenesis, the process of proliferation and differentiation of adipocyte precursor cells, or preadipocytes. Insulin-like growth factor-I (IGF-I) plays a critical role in adipogenesis. We are investigating novel signal transduction pathways used by IGF-I to mediate proliferation and differentation of adipocytes in vitro. Our previous work identified Src as a critical mediator of IGF-I-activated Shc and MAPK in preadipocyte proliferation. We demonstrated that loss of Src-activated MAPK occurs with growth arrest, thus allowing IGF-I to promote adipocyte differentiation through the IRS/PI3K/AKT pathway. We have identified a novel, multi-protein signaling complex including integrins and the focal adhesion kinase Pyk2 that mediates IGF-I action in proliferation. Ongoing studies will determine the mechanism of IGF-I activation of integrins and assembly of the multi-protein complex in preadipocyte proliferation; in addition, studies will elucidate the complex change in signaling that occurs at growth arrest involving loss of mitogenic signaling and modification of IRS/PI3K/AKT signaling required for adipocyte differentiation.

Principal Investigator: Lifespan Developmental Grant
"Modulation of Mitogenic Signal Transduction in Preadipocyte Differentiation"
Total direct costs: $19,979, 12/1/1996 to 5/31/1998

Principal Investigator: Charles H. Hood Foundation Child
Health Research Grant
"Modulation of Mitogenic Signal
Transduction during Preadipocyte Differentiation"
Total direct costs: $44,740, 1/1/1998 to 12/31/1998

Principal Investigator: Knoll Pharmaceutical Company
Weight Risk Investigators Study Council Grant
"Modulation of Mitogenic Signal Transduction in Preadipocyte Differentiation"
Total direct costs: $79,589, 1/1/1999 to 12/31/2000

Principal Investigator: NIH/NIDDK RO1DK59339
"The Role of Src Kinases in IGF-I-mediated Adipogenesis"
Total Direct Costs: $670,000, 3/15/2002 to 1/31/2007

Boney CM, Verma A, Tucker R, Vohr BR. Metabolic Syndrome in Childhood: Association with Birthweight, Maternal Obesity and Gestational Diabetes. Pediatrics, 2005; 115:e290-296

Sekimoto H, Eipper-Mains J, Sunthorn P, Boney CM. avb3 integrins and Pyk2 mediate IGF-I activation of Src and MAPK in 3T3-L1 cells. Mol Endocrinol, 2005; 19:1859-1867

Sekimoto H, Boney CM. C-terminal Src Kinase modulates Insulin-like Growth Factor-I mitogenic signaling in 3T3-L1 adipogenesis. Endocrinol, 2003; 144:2546-2552

Verma A, Boney C, Tucker R, Vohr BR. Insulin Resistance Syndrome in Women with Prior History of Gestational Diabetes Mellitus. J Clin Endocrinol Metab, 2002; 87:3227-3235

Boney CM, Sekimoto H, Gruppuso PA, Frackelton AR. Src family kinases participate in IGF-I mitogenic signaling in 3T3-L1 cells. Cell Growth Diff, 2001; 12:379-386

Kadmon PM, Noto RB, Boney CM, Goodwin G, Gruppuso PA. Thyroid storm in a child following radioactive iodine (RAI) therapy: A consequence of RAI versus withdrawal of antithyroid medication. J Clin Endocrinol Metab, 2001; 86:1865-1867

Boney CM, Gruppuso PA, Faris RA, Frackelton AR. The critical role of Shc in IGF-I-mediated mitogenesis and differentiation of 3T3-L1 preadipocytes. Mol Endocrinol,2000; 14:805-813

Lefebvre D, Boney CM, Ketelsllegers JM, Thissen JP. Inhibition of insulin-like growth factor-I mitogenic action by zinc chelation is associated with decreased mitogen-activated protein kinase activation in rat-1 fibroblasts. FEBS Letters, 1999; 449:284-8

Boney CM, Smith RM, Gruppuso PA. Modulation of insulin-like growth factor-1 mitogenic signaling in 3T3-L1 preadipocyte differentiation. Endocrinology, 1998; 139:1638-1644.

Phornphutkul C, Boney CM, Gruppuso PA. A novel presentation of Addison's disease: Hypoglycemia unawareness in an adolescent with IDDM. J Pediat, 1998; 132:882-884.

Boney CM, Fiedorek FT, Paul SR, Gruppuso PA. Regulation of preadipocyte factor-1 gene expression during 3T3-L1 cell differentiation. Endocrinology, 1996; 137:2923-2928.

D'Ercole AJ, Dai Z, Xing Y, Boney CM, Wilkie MB, Lauder JM, Han VKM, Clemmons DR. Brain growth retardation due to the expression of human IGFBP-1 in transgenic mice: An in vivo model for analysis of IGF function in the brain. Dev Brain Res,1994; 82:213-222.

Boney CM, Moats-Staats BM, Stiles AD, D'Ercole AJ. Expression of insulin-like growth factor-I and insulin-like growth factor binding proteins during adipogenesis. Endocrinology, 1994; 135:1863-1868.

Alpha Omega Alpha, September 1987

College of Medicine Special Commendation for Scholarship and Leadership, University of Tennessee, June 1988

Society for Pediatric Research, 2000

Rhode Island Hospital Faculty Teaching Award in Pediatrics, 2001

Dean's Teaching Excellence Award, Brown Medical School, 2004, 2005, 2006, 2007

Member, Intersex Society of North America, Medical Advisory Board, 2003-present

Charles Hood Foundation Scientific Advisory Board, Boston, MA, 2005-2010

Member, USMlE Step 2 Pediatrics Test Material Development Committee,
Natonal Board of Medical Examiners, Philadelphia, PA, 2005-2008

Member, The Endocrine Society, 1996-present

Member, Lawson Wilkins Pediatric Endocrine Society, 1998-present

Member, Society for Pediatric Research, 2000-present

Member, editorial board, Contemporary Pediatrics

Member, March of Dimes Scientific Review Committee 2006-2011