Our Faculty > Thurl E Harris

Thurl E Harris

Thurl E Harris

Education

  • PhD, Baylor University

Primary Appointment

  • Assistant Professor, Pharmacology

Contact

Research Interest(s)

Molecular mechanisms controlling insulin signaling and fat synthesis.

Research Description

As Paleolithic hunter gatherers, the human diet was relatively low in fats and simple carbohydrates.  Technological advances, beginning with the agricultural revolution 12,000 years ago and culminating with the mechanization of food production in the last century, have provided a significant portion of the world’s population with access to inexpensive, energy-dense food.  In the modern age the ready availability of carbohydrates and fats, combined with a large reduction in physical labor, has lead to a predictable rise in obesity.  Two thirds of the U.S. population is defined as overweight or obese. As an underlying risk factor for type II diabetes and cardiovascular disease, understanding how obesity promotes the development of these diseases is of extreme importance for worldwide health.

Food intake triggers the release of insulin, an anabolic hormone that promotes nutrient storage and protein synthesis.  Mechanisms underlying the storage of carbohydrates and fats as triacylglycerol (TAG) in adipose tissue and the dysregulation of insulin signaling that occurs during obesity are the primary focus of the laboratory.

Triacylglcyerol Storage in Adipocytes and Inflammation –An important research interest in the laboratory are the enzymatic pathways by which adipocytes store fatty acids as TAG, and the functional consequences of excess TAG storage.  Lipin 1 has dual functions; 1) it is a phosphatidic acid phosphatase (PAP), catalyzing a crucial step in the synthesis of TAG, and 2) is a transcriptional co-activator and co-repressor. How lipin 1 activity is regulated in adipocytes by insulin is a key component of our studies.  Complementary research in the laboratory investigates the link between lipin 1 and inflammation.  As adipocytes accumulate increasing amount of TAG during obesity (hypertrophy) they activate inflammatory pathways that lead to adipocyte dysfunction, macrophage infiltration of adipose tissue, and eventually contribute to peripheral insulin resistance.  We are actively pursuing both the involvement of lipin 1 in the mechanisms that initiate inflammation in adipocytes, as well as changes in lipid metabolites that occur during the development of adipocyte hypertrophy.

The mTOR Signaling Pathway - A key player in the insulin signaling cascade is the mammalian target of rapamycin (mTOR), a highly conserved Ser-Thr phosphatidylinositol 3-kinase-related protein kinase that integrates cellular energy status and growth factors to regulate cellular growth, survival, and metabolism.  mTOR forms two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) each of which catalyzes the phosphorylation of different substrates in response to insulin.  The rapamycin sensitive mTOR complex (mTORC1) contains mTOR, raptor, PRAS40 and LST8, while the rapamycin insensitive mTOR complex (mTORC2) contains mTOR, rictor, LST8 and Sin1.  Under conditions of caloric excess, such as that seen during diet-induced obesity, both arms of the mTOR pathway can be affected.  We study the molecular mechanisms of how insulin signaling activates the two different mTOR complexes, the targets of mTORC1 and 2, and the functional consequences of obesity on mTOR activity.

Selected Publications

  • Schuliga M, Javeed A, Harris T, Xia Y, Qin C, Wang Z, Zhang X, Lee P, Camoretti-Mercado B, Stewart A. TGF-β-Induced Differentiation of Airway Smooth Muscle Cells is Inhibited by FGF-2. American journal of respiratory cell and molecular biology. 2012. PMID: 23239497
  • Fisher B, Gerber J, Leckerman K, Seif A, Huang Y, Li Y, Harris T, Torp K, Douglas R, Shah A, Walker D, Aplenc R. Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia. Leukemia & lymphoma. 2012. PMID: 23163631
  • Falvey C, Rosano C, Simonsick E, Harris T, Strotmeyer E, Satterfield S, Yaffe K. Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults. Diabetes care. 2012. PMID: 23160721
  • Shah S, Carey I, Harris T, DeWilde S, Victor C, Cook D. Do good health and material circumstances protect older people from the increased risk of death after bereavement? American journal of epidemiology. 2012;176(8): 689-98. PMID: 23051600 | PMCID: PMC3472615
  • Harris T, Davenport R, Hurst T, Jones J. Improving outcome in severe trauma: trauma systems and initial management: intubation, ventilation and resuscitation. Postgraduate medical journal. 2012;88(1044): 588-94. PMID: 23014941
  • Mangino M, Hwang S, Spector T, Hunt S, Kimura M, Fitzpatrick A, Christiansen L, Petersen I, Elbers C, Harris T, Chen W, Srinivasan S, Kark J, Benetos A, El Shamieh S, Visvikis-Siest S, Christensen K, Berenson G, Valdes A, Viñuela A, Garcia M, Arnett D, Broeckel U, Province M, Pankow J, Kammerer C, Liu Y, Nalls M, Tishkoff S, Thomas F, Ziv E, Psaty B, Bis J, Rotter J, Taylor K, Smith E, Schork N, Levy D, Aviv A. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Human molecular genetics. 2012;21(24): 5385-94. PMID: 23001564 | PMCID: PMC3510758
  • Chishti T, Harris T, Conroy R, Oakeshott P, Tulloch J, Coster D, Kerry S, Kerry S. How reliable are stroke patients' reports of their numbers of general practice consultations over 12 months? Family practice. 2012. PMID: 22987457
  • Mitra M, Chen Z, Ren H, Harris T, Chambers K, Hall A, Nadra K, Klein S, Chrast R, Su X, Morris A, Finck B. Mice with an adipocyte-specific lipin 1 separation-of-function allele reveal unexpected roles for phosphatidic acid in metabolic regulation. Proceedings of the National Academy of Sciences of the United States of America. 2012;110(2): 642-7. PMID: 23267081 | PMCID: PMC3545773
  • Mitra M, Chen Z, Ren H, Harris T, Chambers K, Hall A, Nadra K, Klein S, Chrast R, Su X, Morris A, Finck B. Mice with an adipocyte-specific lipin 1 separation-of-function allele reveal unexpected roles for phosphatidic acid in metabolic regulation. Proceedings of the National Academy of Sciences of the United States of America. 2012;110(2): 642-7. PMID: 23267081 | PMCID: PMC3545773
  • Wang J, He Y, Fan F, Liu X, Xia S, Liu Y, Harris T, Li H, Huang J, Mao S, Zhu T. Two-phase electrochemical lithiation in amorphous silicon. Nano letters. 2013. PMID: 23323743
  • Zeki Al Hazzouri A, Newman A, Simonsick E, Sink K, Sutton Tyrrell K, Watson N, Satterfield S, Harris T, Yaffe K. Pulse Wave Velocity and Cognitive Decline in Elders: The Health, Aging, and Body Composition Study. Stroke; a journal of cerebral circulation. 2013;44(2): 388-393. PMID: 23321445 | PMCID: NIHMS435911