Michael Blaber, Ph.D. Professor of Biomedical Sciences College of Medicine Florida State University College of Medicine Dept. of Biomedical Sciences 1115 West Call Street Tallahassee, FL 32306-4300 Dr. Blaber's Faculty Profile
Research Interests
Research in the Blaber Laboratory is interdisciplinary and includes aspects of protein chemistry, biophysics, structural biology and enzymology; we are fundamentally a protein chemistry laboratory. The training in the lab is in high demand in both academia and industry, and graduates of the lab have gone on to research positions at the NIH, Pfizer, Amgen, Coulter-Beckman, MD Anderson Cancer Center, Brown University, Izmir Institute of Technology, and India Institute of Technology Guwahati. Specific proteins being studied include human acidic fibroblast growth factor (FGF1), and the human kallikrein-related peptidase family. We have utilized FGF1 as a model system to understand protein structure, folding and stability for many years; however, this protein is also a potent angiogenic factor with application in “angiogenic therapy” to treat ”no option” coronary heart disease. The human kallikreins-related peptidases are a novel family of serine proteases implicated in a variety of cancers and neurodegenerative diseases; specific inhibition of select members of this family may prove useful in novel treatment of such diseases. Human Acidic Fibroblast Growth Factor (FGF1) FGF1 is the broadest-specificity human mitogen known (it causes more types of cells to divide and growth than any other known growth factor). FGF1 is being evaluated by several different drugs companies for use in “angiogenic therapy” – the induced growth of new blood vessels to treat ischemia. Protein folding is a major unsolved problem in modern biochemistry, and protein misfolding contributes to important diseased states (e.g. Alzheimer’s disease). We are using FGF1 as a model protein to better understand issues associated with protein structure, folding and stability. We have constructed dozens of mutant forms of FGF1 designed to probe various aspects of the folding and stability of the protein. Several of these mutants have subsequently been shown to have some remarkable functional consequences, including dramatically enhanced functional properties. In collaboration with industrial partners we are evaluating the use of these mutant forms of FGF1 as potential “second generation” therapeutics. Our biophysical studies of FGF1 have also provided important insights into protein folding and mechanisms of protein evolution - involving gene duplication and fusion events to produce complex architectures from simpler structural motifs. Students have an opportunity to participate in both fundamental and applied research.   The Human Kallikrein-related Peptidases (KLKs) For many years it was believed that the human kallikrein-related peptidase (KLK) family comprised only three members (KLK1-3); however, in the mid-1990’s it was realized that there are actually 15 different members (KLK1-15). The KLKs are serine-type proteases (related to trypsin/chymotrypsin); however, the physiological function of the majority of the human KLKs remains a mystery. We have expressed recombinant forms of several human KLKs and have begun to characterize their function. In particular, KLK6 has been a focus of attention. In collaboration with Dr. Isobel Scarisbrick of the Mayo Clinic, Rochester, we have shown that KLK6 is upregulated in response to damage in the CNS, and inhibition of KLK6 can delay the onset and severity of inflammatory demyelination (i.e. a model of Multiple Sclerosis). We are currently focused upon understanding the regulation of action of the human KLKs – i.e. how they are activated, how they are inhibited, and what are the targets of their activity. We have also solved the x-ray structures of human KLK1 and 6.  We have recently reported details of the human KLK “activome” – the activation relationships between the human KLKs. This information will permit the generation of hypotheses regarding regulatory activation cascades involving the human KLK family.
Current Laboratory Members
Sachiko Inoue Blaber, Laboratory Manager Dr. Jihun Lee, Postdoctoral Research Associate Dr. Akshaya Kumar Meher, Postdoctoral Research Associate Gurunathan Laxmikanthan, Graduate Student Hyesook Yoon, Graduate Student Zhe Xu, Graduate Student Cristina Russo, Graduate Student Liam Longo, Undergraduate Student
Selected References
Activation Profiles and Regulatory Cascades of the Human Kallikrein-related Peptidases, Yoon, H., Laxmikanthan, G., Lee, J., Blaber, S.I., Rodriguez, A., Kogot, J.M., Scarisbrick. I.A. and Blaber, M., J. Biol. Chem. (in press)   Spackling the Crack: Stabilizing Human Fibroblast Growth Factor-1 by Targeting the N- and C-terminus b-strand Interactions, Dubey, V.K., Lee, J., Somasundaram, T., Blaber, S. and Blaber, M., J. Mol. Biol. 371, 256-268 (2007)   The Autolytic Regulation of Human Kallikrein-Related Peptidase 6, Blaber, S., Yoon, H., Scarisbrick, I.A., Juliano, M.A., and Blaber, M. Biochemistry 46, 5209-5217 (2007)   Dynamic Role of Kallikrein 6 in Traumatic Spinal Cord Injury, Scarisbrick, I.A., Sabharwal, P., Blaber, S.I., Cruz, H., Ameednuddin, S., Papke, L.M., Larsen, N., Fehlings, M.G., Reeves, R.K., Blaber, M., Windebank, A.J. and Rodriguez, M., Eur. J. Neurosci. 24, 1457-1469 (2006)   Conversion of type I 4:6 to 3:5 b-turn Types in Human Acidic Fibroblast Growth Factor: Effects upon Structure, Stability, Folding and Mitogenic Function, Lee, J., Dubey, V.K., Somasundaram, T. and Blaber, M. Proteins 62, 686-697(2006)   Redesigning Symmetry-Related "Mini-Core" Regions of FGF-1 to Increase Primary Structure Symmetry: Thermodynamic and Functional Consequences of Structural Symmetry, Dubey, V.K., Lee, J. and Blaber, M., Protein Science 14:2315-2323 (2005)