• Agarwal, Rajesh, Ph.D.
• Anchordoquy, Thomas J., Ph.D.
• Anderson, Peter, Pharm.D.
• Aquilante, Christina, Pharm.D.
• Bain, David L., Ph.D.
• Carpenter, John, Ph.D.
• Franklin, Christopher, Ph.D.
• Hail, Jr., Numsen, Ph.D.
• Irons, Richard D., Ph.D.
• Jones Braun, LaToya, Ph.D.
• Ju, Cynthia, Ph.D.
• Kiser, Jennifer, Pharm.D.
• Kompella Uday B., PhD
• Malkinson, Alvin M., Ph.D.
• Mallela, Krishna M. G., Ph.D.
• Maluf, N. Karl, Ph.D.
• Patel, Manisha, Ph.D.
• Petersen, Dennis R., Ph.D.
• Radcliffe, Richard, Ph.D.
• Ross, David, Ph.D.
• Ruth, James. A., Ph.D.
• Scheinman, Robert I., Ph.D.
• Thompson, John A., Ph.D.
• Vasiliou, Vasilis, Ph.D.

Krishna M. G. Mallela, Ph.D.

Assistant Professor of Biophysical Chemistry, Department of Pharmaceutical Sciences

Mailing address:
4200 E. 9th Ave, C238
Denver, CO 80262

Telephone:
Voice:    303-315-7226
Fax:       303-315-0274
E-Mail:  Krishna.Mallela@uchsc.edu

Affiliations:
Pharmaceutical Sciences Graduate Program
Center for Pharmaceutical Biotechnology
Biomolecular Structure Program
University of Colorado Cancer Center

Training and Education:
B.Sc., P. B. Siddhartha College of Arts and Science, India (Chemistry, Mathematics and Physics)
M.Sc., Central University of Hyderabad, India (Chemistry)
Ph.D., Tata Institute of University of Fundamental Research, Bombay, India (Physical Chemistry)
Postdoctoral Research Associate, University of Pennsylvania (Biophysics)
Research Assistant Professor, University of Pennsylvania, Philadelphia (Biophysics and Biochemistry)

Research Interests:
Research in Dr. Mallela's laboratory focuses on understanding the fundamental mechanisms of protein folding, stability and misfolding, and their applications to pharmaceutical sciences and human disease control. Detailed structural information from his previous work using hydrogen exchange and related experiments indicated the following three physical principles underlying protein folding pathways. (1) Proteins are made up of small cooperative unfolding/folding submolecular units known as foldons. (2) Proteins construct these foldon pieces to progressively build their final native states using the sequential stabilization principle where prior structure guides and templates the subsequent foldons. (3) Optional misfolding errors, which are ubiquitous, can corrupt different naturally occurring on-pathway intermediates and cause intermediates to accumulate by inserting error-repair barriers at different points along the pathway. The first two principles dictate that the folding pathway of a protein is predetermined by its component foldon substructure, and the order of steps is set by the way the foldon units are organized in the native structure. The third principle determines whether the pathway appears to be kinetically 2-state or multi-state or heterogeneous. Preliminary evidence shows that proteins may use the same foldons to control their function. For example, in the case of Cytochrome c, the process that triggers the intracellular apoptotic pathway is the unfolding of its least stable or most flexible foldon.

Teaching:
Graduate Program: PHSC & TXCL 7310 - Fundamentals of Pharmaceutical Sciences
                            TXCL 7561 Drug Metabolism & Pharmacogenetics
Pharm D Program: Science Foundations II PHRD: Biochemistry and Cell Biology

Representative Publications:
Krishna, M.M.G., Maity, H., Rumbley, J.N., and Englander, S.W. (2007) “Branching in the sequential folding pathway of cytochrome c” Protein Science, In Press.
Krishna, M.M.G. and Englander, S. W. (2007) “A unified mechanism for protein folding: Predetermined pathways with optional errors” Protein Science, 16: 449-464.
Krishna, M.M.G., Maity, H., Rumbley, J.N., Lin, Y., and Englander, S.W. (2006) “Order of steps in the cytochrome c folding pathway: Evidence for a sequential stabilization mechanism” Journal of Molecular Biology, 359: 1410-1419.
Maity, H., Maity, M., Krishna, M.M.G., Mayne. L., and Englander, S.W. (2005) “Protein folding: The stepwise assembly of foldon units” Proceedings of the National Academy of Sciences of the United States of America, 102: 4741-4746.
Krishna, M.M.G. and Englander, S.W. (2005) “The N-terminal to C-terminal motif in protein folding and function” Proceedings of the National Academy of Sciences of the United States of America, 102: 1053-1058.
Krishna, M.M.G., Lin, Y., and Englander, S.W. (2004) “Protein misfolding: Optional barriers, misfolded intermediates, and pathway heterogeneity” Journal of Molecular Biology, 343: 1095-1109.
Krishna, M.M.G., Hoang, L., Lin, Y. and Englander, S.W. (2004) “Hydrogen exchange methods to study protein folding” Methods, 34: 51-64.
Krishna, M.M.G., Lin, Y., Mayne, L., and Englander, S.W. (2003) “Intimate view of a kinetic protein folding intermediate: Residue-resolved structure, interactions, stability, folding and unfolding rates, homogeneity” Journal of Molecular Biology, 334: 501-513.
Hoang, L., Maity, H., Krishna, M.M.G., Lin, Y., and Englander, S.W. (2003) “Folding units govern the cytochrome c alkaline transition” Journal of Molecular Biology, 331: 37-43.
Krishna, M.M.G., Lin, Y., Rumbley, J., and Englander, S.W. (2003) “Cooperative omega loops in cytochrome c: Role in folding and function” Journal of Molecular Biology, 331: 29-36.

Keywords: Protein folding, stability and misfolding; Molecular mechanism of disease; Biophysical Chemistry; Biomolecular Spectroscopy.

Curriculum Vitae
Recent Publications
Full List of Mallela Publications
Postdoc position available

Last updated: 2/14/08