The applicant has a funded research program in Leptin and Adipokine Physiology and is a Clinical Research Overseer at the BIDMC and the Joslin Diabetes Center. In addition, he has a well established track record in mentoring clinical researchers. The candidate's immediate goal is to determine the role leptin and other adipokines play in normal physiology and the pathophysiology of disease states in humans. His long-term goal is to further our understanding of adipokine biology which will eventually lead to new treatments for metabolic syndrome, diabetes, cardiovascular disease, and obesity-associated malignancies. In working towards these goals, the candidate has and will continue to be training and establishing a group of outstanding clinical investigators studying complementary aspects of energy homeostasis and metabolic disorders. A K24 award will enable the applicant to realize these goals by providing more protected time for both patient-oriented research and mentoring. The environment for this research is outstanding with many successful faculty involved in this general area of research across the Harvard Medical System. The PI has access to """"""""state of the art"""""""" facilities in the General Clinical Research Center (GCRC) as well as ongoing large cohort studies including the Nurses Health Study and the Health Professionals Study. The indicative research protocols described herein involve the administration of recombinant human leptin in the context of GCRC-based, randomized, placebo-controlled trials, to subjects with hypothalamic amenorrhea or the HIV-associated metabolic syndrome and/or to healthy volunteers to study physiology outcomes, leptin signaling, and/or activation of hypothalamic centers by leptin in humans. Moreover, the PI is presenting some of his studies on the role of adiponectin as the link between obesity, insulin resistance and colon cancer, ranging from large observational cohort studies, to studies of human samples ex vivo, to molecular biology and mechanistic animal studies in the laboratory. The applicant is also actively participating in several other observational cohort studies as well as GCRC-based interventional studies on the treatment of obese diabetic subjects. Human obesity and its associated metabolic disorders are among the largest public health challenges of our time. Understanding the mechanisms underlying these disorders is key to finding safe and effective treatments.

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 #
5K24DK081913-05
Application #
8325619
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2008-09-15
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$121,782
Indirect Cost
$9,021
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Li, L-J; Rifas-Shiman, S L; Aris, I M et al. (2018) Associations of maternal and cord blood adipokines with offspring adiposity in Project Viva: is there an interaction with child age? Int J Obes (Lond) 42:608-617
Farr, Olivia M; Mantzoros, Christos S (2018) Obese individuals with type 2 diabetes demonstrate decreased activation of the salience-related insula and increased activation of the emotion/salience-related amygdala to visual food cues compared to non-obese individuals with diabetes: A preliminary stu Diabetes Obes Metab 20:2500-2503
Perakakis, Nikolaos; Yazdani, Alireza; Karniadakis, George E et al. (2018) Omics, big data and machine learning as tools to propel understanding of biological mechanisms and to discover novel diagnostics and therapeutics. Metabolism 87:A1-A9
Farr, Olivia M; Tuccinardi, Dario; Upadhyay, Jagriti et al. (2018) Walnut consumption increases activation of the insula to highly desirable food cues: A randomized, double-blind, placebo-controlled, cross-over fMRI study. Diabetes Obes Metab 20:173-177
Perakakis, Nikolaos; Mougios, Vassilis; Fatouros, Ioannis et al. (2018) Physiology of Activins/Follistatins: Associations With Metabolic and Anthropometric Variables and Response to Exercise. J Clin Endocrinol Metab 103:3890-3899
Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael et al. (2018) Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism 85:240-249
Farr, O M; Mantzoros, C S (2017) Obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate decreased activation of reward-related brain centers in response to food cues in both the fed and fasting states: a preliminary fMRI study. Int J Obes (Lond) 41:471-474
Perakakis, Nikolaos; Farr, Olivia M; Tuccinardi, Dario et al. (2017) Research advances in metabolism 2016. Metabolism 67:41-53
Perakakis, Nikolaos; Triantafyllou, Georgios A; Fernández-Real, José Manuel et al. (2017) Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 13:324-337
Farr, Olivia M; Mantzoros, Christos S (2017) Sleep apnea in relation to metabolism: An urgent need to study underlying mechanisms and to develop novel treatments for this unmet clinical need. Metabolism 69:207-210

Showing the most recent 10 out of 88 publications