The candidate has a Ph.D. in mathematics, with a strong research background in mathematical physics, including dynamical systems, differential equations, spectral theory, geometry etc. Since 1997 he has been working on an interdisciplinary biomedical study with the University of Virginia (UVA), establishing new bioanalytical tools for modeling of blood glucose fluctuations related to hypoglycemia in IDDM. In April 1999, the candidate joined the department of Internal Medicine at UVA, working on dynamic feedback control of the growth hormone (GH) axis. The studies resulted in the creation of a new deterministic model, describing the male rat GH secretory pattern, and shaped the foundation of the present research/training application. On a research level, we propose to investigate our general hypothesis that a parsimonious feedback model can approximate the secretory pattern in both male and female rats, with the observed gender differences explained solely by parameter transitions. The model will be tested/refined using data collected by other projects and will be further extended to approximate the GH release network in the human. We believe that the results will offer new insights into the functional organization of the neuroendocrine hypothalamo-pituitary mechanisms that mediate the dynamic activity of the GH axis. On a training level, the candidate's immediate goal is to establish a sufficient background in the field of hormone pulsatility that will promote his efforts to approach analytically problems related to GH release in the rodent and human. To meet this goal, the career development plan anticipates two formally different parts. The first half of the award period includes four basic medical courses combined with supervised research. The second half is dedicated exclusively to extensive supervised research in the framework of the research plan. The proposed four-year research/training will be performed at the UVA, a university with rich traditions and a large network of facilities supporting research and education in the life sciences. The candidate will interact extensively with outstanding scholars across multiple laboratories, which will help him to achieve the long-term goal of this award - to become an independent investigator able to apply advanced mathematics in biomedical research related to endocrinology.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25HD001474-03
Application #
6636743
Study Section
Special Emphasis Panel (ZHD1-DRG-S (05))
Program Officer
Winer, Karen
Project Start
2001-06-01
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$103,237
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Johnson, Michael L; Veldhuis, Paula P; Grimmichova, Tereza et al. (2010) Validation of a deconvolution procedure (AutoDecon) for identification and characterization of fasting insulin secretory bursts. J Diabetes Sci Technol 4:1205-13
Evans, William S; Farhy, Leon S; Johnson, Michael L (2009) Biomathematical modeling of pulsatile hormone secretion: a historical perspective. Methods Enzymol 454:345-66
Johnson, Michael L; Pipes, Lenore; Veldhuis, Paula P et al. (2008) AutoDecon, a deconvolution algorithm for identification and characterization of luteinizing hormone secretory bursts: description and validation using synthetic data. Anal Biochem 381:8-17
Iuorno, Maria J; Islam, Leila Z; Veldhuis, Paula P et al. (2007) Leptin secretory burst mass correlates with body mass index and insulin in normal women but not in women with polycystic ovary syndrome. Metabolism 56:1561-5
Farhy, Leon S; Bowers, Cyril Y; Veldhuis, Johannes D (2007) Model-projected mechanistic bases for sex differences in growth hormone regulation in humans. Am J Physiol Regul Integr Comp Physiol 292:R1577-93
Farhy, Leon S; Veldhuis, Johannes D (2005) Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion. Am J Physiol Regul Integr Comp Physiol 288:R1649-63
Erickson, Dana; Keenan, Daniel M; Farhy, Leon et al. (2005) Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp. J Clin Endocrinol Metab 90:1741-51
Soares-Welch, Cacia; Farhy, Leon; Mielke, Kristi L et al. (2005) Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults. J Clin Endocrinol Metab 90:2225-32
Veldhuis, Johannes D; Farhy, Leon; Weltman, Arthur L et al. (2005) Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults. J Clin Endocrinol Metab 90:2874-81
Veldhuis, Johannes D; Erickson, Dana; Mielke, Kristi et al. (2005) Distinctive inhibitory mechanisms of age and relative visceral adiposity on growth hormone secretion in pre- and postmenopausal women studied under a hypogonadal clamp. J Clin Endocrinol Metab 90:6006-13

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