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James L. McManaman, Professor

Ph.D. (1978) University of Colorado, Boulder



Departments of Obstetrics &Gynecology, Physiology and Biophysics
Chief, Division of Basic Reproductive Sciences
Director, Graduate Program in Integrated Physiology 

Mail Stop 8613
RC-2 , P15-3013
Phone: 303-724-3500
Fax     303-724-3512

Jim.McManaman@UCDenver.edu

Research in the McManaman laboratory investigates how cells store, metabolize, and traffic lipids at the molecular, structural, cellular and organ systems levels.  We use biochemical, molecular modeling, and live-cell imaging approaches to define the basic mechanisms by which cells store and traffic lipids.  We use mouse genetic models and systems biology approaches, including proteomics and metabolomics, to understand the molecular physiology of lipid storage, metabolism and secretion, and how disruption of these processes contribute to metabolic disorders such as obesity.   Major areas of research in the laboratory include:

Regulation of cellular lipid storage and utilization.  In eukaryotic cells, specialized organelle-like structures, termed cytoplasmic lipid droplets (CLD), regulate storage, utilization, and trafficking of lipids.  Perilipins are a family of CLD scaffolding proteins that are required for CLD formation, and that modulate the lipid storage and trafficking functions of CLD.  A primary focus in this area of research is to define the molecular and structural features of perilipin’s that mediate their scaffolding properties and that control the biological functions of CLD.

new Plin2 domain and legend.jpg​​​​​​

Molecular Systems Biology of Lipid Metabolism.  Imbalances in lipid metabolism are central features of obesity, diabetes, hypertension, heart disease and cancer.  Projects in the laboratory are directed at understanding the mechanisms by which cells balance lipid metabolism at the molecular, ultrastructural and systems levels, and how disruption of these processes leads to metabolic dysregulation and disease.  Research in this area focuses on the cell biology of CLD and the consequences of disrupting their functions on the cells metabolic properties.

new CLD organelle.jpg

Defining the intergenerational determinants of metabolic health.​​​A mother’s metabolic state can influence the health of her children.  Projects in the laboratory use transgenic mouse models to understand the molecular and physiological mechanisms that underlie the effects of obesity on maternal adaptations to pregnancy and lactation, and how maternal metabolic abnormalities lead to impaired neonatal growth and metabolism.  

Media Coverage of Research:​

CU Researchers slim down mice by deleting obesity gene​

Denver Post: Fat Cure?​

Obesity Gene​

CU researchers one step closer to combating obesity​

Orlicky, D.J., Degala, G. Greenwood, C., Bales, E.S., Russell, T.D. and McManaman, J.L. Multiple Functions Encoded by the N-terminal PAT domain of Adipophilin, J. Cell Sci. 121: 2921-2929, 2008

Huang, X., Gao, L., Wang, S. McManaman, J.L., Thor, A.D., Yang, XH, Esteva, F.J. and Liu, B. Heterotrimerization of ErbB3/ErbB2/IGF-1R in Trastuzumab-resistant Breast Cancer Cells, Canc Res 70: 1204-1214, 2010

Strong foreign promoters contribute to innate inflammatory responses induced by adenovirus transducing vectors, Virol. 312: 28-35, 2011

Chong, B.M., Russell, T.D., Schaack, J., Orlicky, D.J., Reigan, P., Ladinsky, M. and McManaman, J.L. The adipophilin C-terminus is a self-folding membrane binding domain that is important for milk lipid secretion, J. Biol. Chem. 286: 23254-23265, 2011

Orlic

ky, D.J., Roede, J. Bales, E., Greenwood, C., Greenberg, A., Petersen, D. and McManaman, J.L.  Chronic ethanol consumption in mice alters lipid droplet properties. Alcoholism: Clinc. Expt. Res. 35: 1020-1033, 2011

Chong, B.M., Reigan, P., Mayle-Combs, K.D., Orlicky, D.J. and McManaman, J.L. Determinants of adipophilin function in milk lipid formation and secretion.  Trends Endocrionol. Metab.  22: 211-217, 2011

Russell, T.D., Schaack, J., Orlicky, D.J., Palmer, C.A., Chang, B. H-J., Chan, L. and McManaman, J.L. Adipophilin regulates cytoplasmic lipid droplet accumulation and alveolar maturation in differentiating nulliparous mouse mammary glands J. Cell Sci. 124: 3247-3253, 2011. 


Latest Publications in PubMed