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Hedley C. Freake

Professor

Email: hedley.freake@uconn.edu

Research Interests

My laboratory uses molecular approaches to address questions of nutritional significance. There are two overlapping areas of study. The first is the regulation of long chain fatty acid synthesis by hormones and diet, in particular thyroid hormones and dietary carbohydrate. This regulation, which appears to be transcriptional in nature, varies depending on the tissue in question. For example, lipogenesis in liver is extremely sensitive to changes in thyroid hormone or dietary status, whereas the process is unaffected in other actively lipogenic tissues, such as lung and brain. We are seeking to determine the molecular differences between tissues which explain this differential regulation. The second area relates to the trace mineral zinc, which has recently been implicated in the pathway by which several hormones, including thyroid hormone, regulate gene expression. We are assessing the extent to which thyroid hormone action depends on zinc, using both bacterially expressed human thyroid hormone receptors and a well-characterized thyroid hormone responsive cell line. This work has now been extended, in collaboration with faculty in the Departments of Chemistry and Animal Science, to a more basic investigation of zinc homeostasis and action.

Longer research summaries may be found below under Recent funding

Teaching Interests

At the undergraduate level, I teach NUSC165 Fundamentals of Nutrition, which is an introductory course taken by a wide range of students. The number of students and the amount of information requires a lecture format, for the most part, which I break up with discussion and other activities. I enjoy making the complexities of the science of nutrition alive and interesting.

At the graduate level, I teach NUSC301 Concepts of Nutrition, which is required of all entering graduate students. Its prime goal is to introduce nutrition as a research discipline. The course also serves to introduce the new students to each other and to an unfamiliar academic environment. The very active participation of all students is expected and occurs.

A second graduate course, NUSC313 Nutrition and Gene Expression is co-taught with Mary McGrane. It is offered in the spring semester of odd numbered years. The course introduces students to the world of molecular biology and discusses the latest findings in this area of nutrition research.

A general philosophy which guides my approach to teaching is a belief that all students are inherently intelligent. My job is to assist them with the skills required for the accessing and thoughtful evaluation of information, which leads to a successful learning experience.

Education

  • 1983-86 - Fellowship in Molecular Endocrinology, Department of Medicine, University of Minnesota
  • 1979-83 - Ph.D. degree in Physiology, Royal Postgraduate Medical School, University of London
  • 1976-79 - B.Sc. degree in Nutrition, first class honours, Queen Elizabeth College, University of London

Employment

  • 2002-present - Professor of Nutritional Sciences and Molecular and Cell Biology, University of Connecticut
  • 2001-present - Affiliate Associate Professor of Animal and Nutritional Sciences, University of New Hampshire
  • 1994-2002 - Associate Professor of Nutritional Sciences and Molecular and Cell Biology, University of Connecticut
  • 1988-94 - Assistant Professor of Nutritional Sciences and Molecular and Cell Biology, University of Connecticut
  • 1983-88 - Postdoctoral Fellow and Research Associate in the laboratory of Dr Jack Oppenheimer, Department of Medicine, University of Minnesota
  • Research Associate in the laboratory of Professor Iain MacInytre, Royal Postgraduate Medical School, University of London

Other Scholarly Activities

  • 2006-2009  Member University Senate Executive Committee
  • 2005-present.  Director, STRONG-CT, Science and Technology, Reaching Out to New Generations in Connecticut program.
  • 2004-present - Chair, General Education Oversight Committee, University of Connecticut
  • 2003-2004 - Chair, Faculty Staff Mentoring Committee, University of Connecticut
  • 2003-2005 - Editorial Advisory Board, Encyclopedia of Human Nutrition
  • 2001 - Co-organizer, FASEB Summer Conference on Molecular Mechanisms of Regulation by Dietary Constituents, Saxtons River , VT
  • 2000-2005 - American Society for Nutritional Sciences, Long Range Planning Committee. Chair 2001-2004.
  • 2000 - Chairperson, USDA subcommittee for FASEB Consensus Conference on Federal Funding for Biomedical and Related Life Science Research FY2002
  • 1999-2000 - Chair, Nutrient-Gene Interaction Research Interest Section, American Society for Nutritional Sciences
  • 1998-2004 - Editorial Board, Journal of Nutrition
  • 1998-2001 - Contributing Editor, Nutrition Reviews
  • 1998-present - University Senate
  • 1990 - Elected to American Institute of Nutrition/American Society for Nutritional Sciences

Recent Publications

  • Aggarwal D, Freake HC, Soliman GA, Dutta A, Fernandez ML.  Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism.  Lipids Health Dis. 15:22, 2006.
  • Freake HC.  Iodine.  In: Biochemical, Physiological and Molecular Aspects of Human Nutrition. 2nd edition.  Stipanuk M, ed.  Saunders Elsevier, St Louis, MO, pp 1068-1090.  2006.
  • Kim YJ, Lee MS, Lee HJ, Wu Y, Freake HC, Chun HS, Kim Y.  Hormones and nutrients regulate acetyl-CoA carboxylase promoter I in rat primary hepatocytes.  J Nutr Sci Vitaminol 51,124-128, 2005.
  • Berdanier, Catherine and Freake, Hedley  Nutrient Gene Interactions, Health Implications. In: Encyclopedia of Human Nutrition, 2nd edition. Editors Benjamin Caballero, Lindsay Allen and Andrew Prentice.  Elsevier, 2005.
  • Berdanier, Catherine and Freake, Hedley  Nutrient Gene Interactions, Molecular Aspects. In: Encyclopedia of Human Nutrition, 2nd edition. Editors Benjamin Caballero, Lindsay Allen and Andrew Prentice.  Elsevier, 2005.
  • Patalay M, Lofgren IE, Freake HC, Koo SI and Fernandez ML. The lowering of plasma lipids following a weight reduction program is related to increased expression of the LDL receptor and lipoprotein lipase. J Nutr135, 735-739, 2005.
  • Lim NC, Freake HC and Bruckner C.  Illuminating zinc in biological systems.  Chem Eur J 11, 38-49, 2005.
  • Lim NC, Schuster JV, Porto MC, Tanundra MA, Yao L, Freake HC and Bruckner C.  Coumarin-based chemosensors for zinc(II): toward the determination of the design algorithm for CHEF-type and ratiometric probes.  Inorg Chem 44, 2018-2030, 2005.
  • Freake Hedley   Zinc. Berdanier, Catherine and Freake, Hedley  Nutrient Gene Interactions, Molecular Aspects. Berdanier, Catherine and Freake, Hedley  Nutrient Gene Interactions, Health Implications. All in: Encyclopedia of Human Nutrition, 2nd edition. Editors Benjamin Caballero, Lindsay Allen and Andrew Prentice.  Elsevier, 2005.
  • Zeisel SH, Freake HC, Bauman DE, Bier DM, Burrin DG, German JB, Klein S, Marquis GS, Milner JA, Pelto GH, Rasmussen KM. The nutritional phenotype in the age of metabolomics. J Nutr. 135, 1613-6, 2005.
  • German JB, Bauman DE, Burrin DG, Failla ML, Freake HC, King JC, Klein S, Milner JA, Pelto GH, Rasmussen KM, Zeisel SH.  Metabolomics in the opening decade of the 21st century: building the roads to individualized health.  J Nutr. 134, 2729-32, 2004.
  • Lim NC, Schuster JV, Porto MC, Tanundra MA, Yao L, Freake HC and Bruckner C. Coumarin-based chemosensors for zinc(II): toward the determination of the design algorithm for CHEF-type and ratiometric probes.  Inorg Chem 44, 2018-2030, 2005.
  • Lim NC, Freake HC and Bruckner C.  Illuminating zinc in biological systems.  Chem Eur J 11, 38-49, 2005.
  • Sciaudone MP, Yao L, Schaller M, Zinn SA and Freake HC. Diethylenetriaminepentaacetic acid enhances thyroid hormone action by a transcriptional mechanism. Biological Trace Element Research. 99, 219-231, 2004.
  • Lim, N. C., Yao, L., Freake HC. and Brückner, C., Synthesis of a fluorescent chemosensor suitable for the imaging of zinc(II) in live cells. Bioorg. Med. Chem. Lett. 13, 2251-2254, 2003.
  • Pelto GH and Freake HC. Social research in an integrated science of nutrition: future directions. J Nutr. 2003 Apr;133(4):1231-4.
  • Moon YK and Freake HC. Nutritional and hormonal regulation of lipogenesis in rat white and brown adipocytes. J Nutr Sci Vitaminol. 49, 40-46, 2003.
  • Vega-Lopez S, Freake HC and Fernandez ML. Sex and hormonal status modulate the effects of psyllium on plasma lipids and monocyte gene expression in humans. J Nutr, 133, 67-70, 2003.
  • Ramjiganesh T, Roy S, Freake HC, McIntyre JC and Fernandez ML. Corn fiber oil lowers plasma cholesterol by altering hepatic cholesterol metabolism and upregulating LDL receptors in guinea pigs. J Nutr, 132, 335-340,2002.
  • Roy S, Freake HC and Fernandez ML. Gender and hormonal status affect the regulation of hepatic cholesterol 7alpha-hydroxylase activity and mRNA abundance by dietary soluble fiber in the guinea pig. Atherosclerosis,163, 28-37, 2002.
  • Freake HC, Govoni KE, Guda K, Huang C and Zinn SA. Actions and interactions of thyroid hormone and zinc status in growing rats. J Nutr,131, 1135-1141, 2001.
  • Zeisel SH, Allen LH, Coburn SP, Erdman JW, Failla ML, Freake HC, King JC and Storch J. Nutrition: a reservoir for integrative science. J Nutr,131, 1319-1321, 2001.
  • O'Callaghan B, Koo S-H, Wu Y, Freake HC and Towle HC. Glucose regulation of the acetyl-coA carboxylase PI promoter in rat hepatocytes. J Biol Chem, 276, 16033-16039, 2001.

Recent Funding

STRONG-CT, Science and Technology, Reaching Out to New Generations in Connecticut.
10/1/05-9/30/10.  NSF-STEP $1,999,905.  C0-PIs Damon Williams, Eleanor Weseloh, Diba Khan-Bureau and Melissa Philion.

Cellular zinc transport.
10/1/04-9/30/07.  USDA/Hatch.  $29,000 (approx).

Characterization and responsiveness of proteins key to zinc homeostasis in cultured cells.
6/1/2003-5/31/2004. UConn Research Foundation $6,081.

Fluorescent probes for intracellular zinc detection.
1/1/2002-12/31/2002. UConn Research Foundation $16,568. Co-PI, PI Christian Bruckner.

Capillary electrophoresis to enable zinc speciation for studies of zinc homeostasis.
7/1/02-6/30/03. USDA/NRICGP/Equipment $26,473 (plus $26,473 matching from internal sources at the University of Connecticut). Co-PI, PI Robert Michel.

Effects of zinc on nuclear actions of thyroid hormone.
11/1/00-10/31/03, USDA/NRICGP $130,000 (S Zinn, ANSC, Co-PI).

Molecular Mechanisms of Thyroid Hormone Regulation of Lipogenesis
USDA/Hatch CONS00665

Thyroid hormone (T3) regulates fatty acid synthesis in the rat in a tissue specific manner. The largest effects are seen in liver, whereas tissues such as brain and lung are non-responsive. Parallel changes occur in levels of mRNA encoding acetyl-CoA carboxylase (ACC) and fatty acid synthase, indicating the pretranslational location of these effects. In white adipose tissue, lipogenesis is inhibited in the hyperthyroid state, despite elevated levels of lipogenic mRNAs. However, in cultured adipocytes, T3 directly enhances both fatty acid synthesis and lipogenic mRNA expression, suggesting that the inhibitory effects of hyperthyroidism on lipogenesis in vivo are secondary, presumably at the level of ACC activity. In brown adipose tissue, lipogenesis and associated mRNAs are highest in the hypothyroid state. However effects of T3 in cultured brown adipocytes are stimulatory, again indicating secondary effects of hypothyroidism in vivo. The ACC gene has a complex structure including two promoters (PI and PII) and splicing variations in the 5'-untranslated region giving rise to multiple mRNAs. We have used the reverse transcription-polymerase chain reaction to investigate the tissue specific use of these promoters. We find that PII products are uniformly expressed across all tissues examined. PI expression is more variable, with appreciable levels only being found in liver and adipose tissues. Furthermore, levels of mRNA produced from PI are increased by T3 treatment, whereas those derived from PII are unaffected. The PI, but not the PII, promoter is also responsive to starving/refeeding suggesting that PI is responsible for adjusting fatty acid synthesis to changing physiological situations, whereas PII directs basal enzyme activity.

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