The overall goal of this project is to support my continued professional development as an independent patient-oriented investigator and successfull mentor. My recent research focus has been to establish and validate optimal biochemical endpoints for the therapy of acromegaly. In these efforts, I have established a uniquely large cohort of patients, re-defined its biochemical criteria based on highly sensitive GH and IGF-I measurements and investigated novel therapeutic approaches to this disease. From these studies, we recognized the need to validate the biochemical endpoints for treatment against clinical disease activity in order to ensure truly """"""""normal"""""""" clinical GH/IGF-I status. The scientific aims of this application correlate modern biochemical markers with short and long-term clinical outcomes and with metabolic and clinical disease activity in our cohort. The first 4 aims, funded by R01 DK06420 for which I am the PI, investigate the use of body composition to gauge disease activity, therapy with the novel GH receptor antagonist, pegvisomant, and the effect of dysregulated ghrelin secretion on biochemical and clinical disease activity markers in acromegaly. Two new aims extend those of my R01, investigating, in Aim 5, IGF-I levels as a markers of insulin sensitivity and body composition in acromegaly and in Aim 6, IGF-I as a marker of cardiovascular structure and function during therapy with the GH receptor anagonist, pegvisomant. These studies aim to improve our understanding of the optimal therapeutic endpoints and, in particular, our serum IGF-I goals for the treatment of acromegaly. My productive, ongoing, NIH funded clinical research program and 12 years of experience in patient-oriented research make me well suited to receive the K24 award. The additional funds provided by the K24 would allow me to raise my effort of NIH research support commensurate with the amount of time I currently commit to patient-oriented research and mentoring and also allow me to continue to expand in both these areas. The institutional environment at Columbia University, with a strong and diverse Endocrine Division, GCRC, Diabetes and Obesity Research Centers, is ideal for attracting fellows and conducting our research. The Mid-career Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support I need to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK073040-03
Application #
7279930
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2005-09-30
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$137,918
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Carminucci, Arthur S; Ausiello, John C; Page-Wilson, Gabrielle et al. (2016) OUTCOME OF IMPLEMENTATION OF A MULTIDISCIPLINARY TEAM APPROACH TO THE CARE OF PATIENTS AFTER TRANSSPHENOIDAL SURGERY. Endocr Pract 22:36-44
Geer, Eliza B; Lalazar, Yelena; Couto, Lizette M et al. (2016) A prospective study of appetite and food craving in 30 patients with Cushing's disease. Pituitary 19:117-26
Reyes-Vidal, Carlos M; Mojahed, Hamed; Shen, Wei et al. (2015) Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment. J Clin Endocrinol Metab 100:2946-55
Reid, Tirissa J; Jin, Zhezhen; Shen, Wei et al. (2015) IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition. Pituitary 18:808-19
Zabarovskaja, Stanislava; Freda, Pamela; Williams, Jill J et al. (2014) Acylation of ghrelin is increased in heart failure and decreases post heart transplantation. Scand Cardiovasc J 48:343-8
Reyes-Vidal, Carlos; Fernandez, Jean Carlos; Bruce, Jeffrey N et al. (2014) Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. J Clin Endocrinol Metab 99:4124-32
Geer, Eliza B; Shen, Wei; Strohmayer, Erika et al. (2012) Body composition and cardiovascular risk markers after remission of Cushing's disease: a prospective study using whole-body MRI. J Clin Endocrinol Metab 97:1702-11
Thearle, Marie S; Freda, Pamela U; Bruce, Jeffrey N et al. (2011) Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor. Pituitary 14:418-24
Lund, Lars H; Freda, Pamela; Williams, Jill J et al. (2010) Leptin resistance after heart transplantation. Eur J Heart Fail 12:516-20
Geer, Eliza B; Shen, Wei; Gallagher, Dympna et al. (2010) MRI assessment of lean and adipose tissue distribution in female patients with Cushing's disease. Clin Endocrinol (Oxf) 73:469-75

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