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Marcos Milla

MARCOS E. MILLA , Ph.D.

Assistant Professor of Biochemistry and Biophysics

Location: 805B Stellar-Chance Building / 6059
Tel: (215) 898-7500
Fax: (215) 573-4764
Email: mmilla@mail.med.upenn.edu

Ph.D. Saint Louis University (1990)

DESCRIPTION OF RESEARCH INTERESTS:

Dr. Milla's laboratory is interested in mammalian cell signal transduction, looking at the conformational changes, protein-protein interactions and subcellular distribution of proteins mediating intracellular signalling, using a combination of approaches from biophysical chemistry, molecular and structural biology. He is focusing on two model systems for these studies:

• The conversion of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF- a ) from its membrane-bound precursor form into the secreted mature form by the TNF- a converting enzyme (TACE). For this, the biogenesis, structure, function and regulation of TACE are being investigated both in vivo and in vitro.
• Structure and function studies on the bone-degrading cytokine RANKL (receptor activator of NFkB ligand) and its interaction with the cellular receptor RANK and the soluble, scavenging receptor Osteoprotegerin.

1. Leonard, J. D., Lin, F. and Milla, M. E. (2004) Chaperone-like properties of the pro-domain of TACE and the role of its cysteine switch. Biochem. J. , (In press)
2. Gonzales, P., Solomon, A., Leesnitzer, M.A., Miller, A.B., Sagi, I. and Milla, M. E. (2004) Inhibition of TACE by its pro domain. J. Biol. Chem . 279 :31638-31645
3. Solomon, A., Rosenblum, G., Gonzales, P. E., Leonard, J. D., Mobashery, S., Milla, M. E. and Sagi, I. (2004) Pronounced chemical diversity between the catalytic zinc sites of TACE and MMPs despite of their high structural homology. J. Biol. Chem. 279 :31646-31654
4. Hinkle, C. L., Mohan, M. J., Lin, P., Yeung, N., Rasmussen, F., Milla, M. E. and Moss, M. L. (2003) Multiple metalloproteinases process protransforming growth factor- a (ProTGF- a ). Biochemistry 42 :2127-2136.
5. Mohan, M. J., Seaton, T., Hassler, D., Blackburn, R. K., Burkhart, W., Moyer, M., Mitchell, J., Waitt, S., Becherer J. D., Moss, M. L. and Milla, M. E. (2002) Substrate requirements of the Tumor Necrosis Factor-Alpha Converting Enzyme (TACE). Biochemistry 41 :9462-9469.
6. Milla, M. E., Leesnitzer, M. A., Moss, M. L., Clay, W. C., Carter, H. L., Miller, A. B., Su, J.-L., Lambert, M. H., Willard, D. H., Sheeley, D. M., Kost, T. A., Burkhart, W., Moyer, M., Blackburn, R. K., Pahel, G. L., Mitchell, J. L., Hoffman, C. R. and Becherer, J. D. (1999) Specific sequence elements are required for the expression of functional Tumor Necrosis Factor-Alpha Converting Enzyme (TACE). J. Biol. Chem . 274 :30563-30570.
7. Skovronsky, D.M., D.B. Moore, M.E. Milla, R.W. Doms and V.M.-Y. Lee (2000) Protein kinase C-dependent a -secretase competes with ß -secretase for cleavage of amyloid- ß precursor protein in the trans-Golgi network. J. Biol. Chem . 275 :2568-2575.
   
8. Skovronsky, D.M., S. Fath, V.M.-Y. Lee and M.E. Milla (2001) Neuronal expression of TACE and its correlation to ß -amyloid plaques. J. Neurobiol . 49 :40-46.