All three projects rely on genetically modified mice and the production of purified proteins and polyclonal and monoclonal antibodies. Accordingly, all three projects will be supported by the Mouse Model and Protein Expression Core (Core A), led by Dr. Loren Fong. Dr. Fong is an expert in a wide variety of practical techniques in cellular and molecular biology, including growing and manipulating mouse embryonic stem cells and the use of mouse models in biomedical research. This expertise has paid huge dividends for this PPG. Dr. Fong, working with Drs. Reue, Young, and Tontonoz, has generated conventional and tissue- specific Lipin2, Lipin3, Idol, and Tle3 knockout mice. In addition, the Core houses and genotypes mice, backcrosses mice onto inbred strains, maintains animal protocols, and organizes histological studies on mouse models. The Core also produces purified proteins for biochemical studies and for generating polyclonal and monoclonal antibodies; this has been an essential function, since our PPG has focused on newly discovered molecules, for which few reagents exist. During the prior funding period, Drs. Bensadoun, Fong and Young produced multiple antibody reagents for this PPG. Their expertise and experience will be a boon for the new antibody projects proposed in this application. Aside from antibody reagents, the Core will also produce purified recombinant proteins for biochemical and structural biology studies. All three projects of the PPG will use Core A.

Public Health Relevance

This Program Project Grant proposes to define the molecular mechanisms that regulate lipid metabolism and adiposity-two events that play centrol roles in the pathogenesis of metablic disesase (e.g., obeisity and atherosclerosis). The Mouse Model and Protein Expression Core will support the PPG's goals by providing new mouse models, antibodies, and recombinant proteins to all three projects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL090553-09
Application #
9195124
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Olive, Michelle
Project Start
2008-08-01
Project End
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kristensen, Kristian K; Midtgaard, Søren Roi; Mysling, Simon et al. (2018) A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase. Proc Natl Acad Sci U S A 115:E6020-E6029
Allan, Christopher M; Heizer, Patrick J; Jung, Cris J et al. (2018) Palmoplantar keratoderma in Slurp1/Slurp2 double-knockout mice. J Dermatol Sci 89:85-87
He, Cuiwen; Weston, Thomas A; Jung, Rachel S et al. (2018) NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes. Cell Metab 27:1055-1066.e3
Larsson, Mikael; Allan, Christopher M; Heizer, Patrick J et al. (2018) Impaired thermogenesis and sharp increases in plasma triglyceride levels in GPIHBP1-deficient mice during cold exposure. J Lipid Res 59:706-713
Goldberg, Ira J; Reue, Karen; Abumrad, Nada A et al. (2018) Deciphering the Role of Lipid Droplets in Cardiovascular Disease: A Report From the 2017 National Heart, Lung, and Blood Institute Workshop. Circulation 138:305-315
Rajbhandari, Prashant; Thomas, Brandon J; Feng, An-Chieh et al. (2018) IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure. Cell 172:218-233.e17
He, Cuiwen; Hu, Xuchen; Weston, Thomas A et al. (2018) Macrophages release plasma membrane-derived particles rich in accessible cholesterol. Proc Natl Acad Sci U S A 115:E8499-E8508
Zhang, Li; Rajbhandari, Prashant; Priest, Christina et al. (2017) Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. Elife 6:
Hu, Xuchen; Sleeman, Mark W; Miyashita, Kazuya et al. (2017) Monoclonal antibodies that bind to the Ly6 domain of GPIHBP1 abolish the binding of LPL. J Lipid Res 58:208-215
Allan, Christopher M; Larsson, Mikael; Jung, Rachel S et al. (2017) Mobility of ""HSPG-bound"" LPL explains how LPL is able to reach GPIHBP1 on capillaries. J Lipid Res 58:216-225

Showing the most recent 10 out of 143 publications