My primary research interest involves rational development of antisickling agents to treat sickle cell anemia, and also antiischemic agents that may be useful for the treatment of brain tumors with irradiation, heart diseases (unstable angina), blood loss, wound healing, and as blood additives to lengthen the storage life of blood. The research integrates molecular modeling, synthesis, testing, biological evaluation, and x-ray crystallography to design small molecules to bind to human pyruvate kinase and hemoglobin proteins.

Other research interests include x-ray structure determination and structure-function studies of (1) hemoglobin; (2) enzymes in Vitamin B6 Metabolism: The goal of the research is to elucidate the structures of the enzymes that are involved in the metabolic cycle of vitamin B6 and to elucidate how nutritional insufficiency in levels of folic acid and vitamin B6 affect the metabolic pathways in homocysteine metabolism.; and (3) methicillin inhibitor (MecI): A transcriptional inhibitor that binds promotor-operator of methicillin resistance gene in staphylococcus aurerus and functions as an antibiotic resistance protein. The long-term goals would be to translate the basic understandings of the results from these researches into therapeutic agents.

Selected Patents and Publications:
D. J. Abraham, M. K. Safo, T. Boyiri, and R. E. Danso-Danquah. "Aldehydic Agents for Allosteric Modification of Hemoglobin". US Patent No. 5,599,974.

D. J. Abraham, G. S. Joshi, S. J. Hoffman, M. Grella, R. Danso-Danquah, A. Yousseff, M. K. Safo, S. Kulkarni. "Substituted Chiral Allosteric Hemoglobin Modifiers". US Patent No. 6,486,342 B1, 2002.

L. W. Hardy, D. J. Abraham, and M. K. Safo in D. J. Abraham, Ed., Burger’s Medicinal Chemistry and Drug Discovery, Vol. 1, Structure-based Drug Design, John Wiley and Sons, Inc., Hoboken, NJ, 2002, p.417.

M. K. Safo, J. C. Burnett, F. N. Musayev, S. S. Nokuri, and D. J. "Abraham Crystal Structure of Human Carbonmonoxy Hemoglobin at 2.16 Å: A Snapshot of the Allosteric Transition" Acta Crystallog., Sec. D58, 2031-2037.

M. L. di Salvo, T.-P. Ko, F. N. Musayev, S. Raboni, V. Schirch, and M. K. Safo. "Active Site Structure and Stereospecificity of Escherichia coli Pyridoxine 5'-phosphate Oxidase" J. Mol. Biol. 315, 2002, 385-397.

M. C Marden, M. Cabanes-Macheteau, A. Babes, L. Kiger, N. Griffon, C. Poyart, T. Boyiri, M. K. Safo, D. J. Abraham. "Control of the allosteric equilibrium of hemoglobin by cross-linking agents". Protein Sci. 11, 2002, 1376-83

M. K. Safo, T. Boyiri, J. C. Burnett, R. Danso-Danquah, C. M. Moure, G. S. Joshi and D. J. Abraham. "X-ray Crystallographic Analyses of Symmetrical Allosteric Effectors of Hemoglobin. Compounds Designed to Link Primary and Secondary Binding Sites". Acta Crystallogr Sec. D. 58, 2002, 634-44.

A. M. Youssef, M. K. Safo, R. Danso-Danquah, G. S. Joshi, J. Kister, M. Marden, and D. J. Abraham. "Synthesis and X-ray Studies of Chiral Allosteric Modifiers of Hemoglobin". J. Med. Chem. 2002, 45, 1184-95.

M. K. Safo, F.N.Musayev, M.L.Di Salvo, and V.Schirch. X-ray structure of Escherichia coli pyridoxine 5'-phosphate oxidase complexed with Pyridoxal 5'-phosphate at 2.0 Å resolution. J. Mol. Biol. 310, 2001, 817-826.

M. K. Safo, D. J. Abraham. "Refined Crystal Structure of Bovine Carbonmonoxy Hemoglobin at 2.1 Å Resolution". PROTEIN SCI. 10, 2001, 1091.

M. K. Safo, C. M. Moure, James Burnett, G. S. Joshi, and D. J. Abraham. "High Resolution Crystal Structure of Deoxy T-state Hemoglobin Complexed with a Potent Allosteric Effector". PROTEIN SCI. 10, 2001, 951-957.

M K. Safo, F. N. Musayev, S.-H. Wu, D. J. Abraham and T.-P. Ko. "Structure of Tetragonal Crystals of Human Erythrocyte" Catalase Acta Crystallog., Sec.. D57, 2001, 1-7.

M. P. Grella, R. Danso-Danquah, M. K. Safo, G. S. Joshi, J. Kister, S. J. Hoffman, M. Marden, and D. J. Abraham "Synthesis and Structure-Activity Relationships of Chiral Allosteric Modifiers of Hemoglobin". J. Med. Chem.43, 2000, 4726-4737

T.-P. Ko, M. K. Safo, F. N. Musayev, M. L Di Salvo, C. Wang, S.-H. Wu and D. J. Abraham. "Crystal Structure of Human Erythrocyte Catalase". Acta Crystallog., Sec. D56, 2000, 241-245.

M. K. Safo, I. Mathews, F.N.Musayev, M.L.Di Salvo, D.Thiel, D.J.Abraham and V.Schirch. "X-ray structure of Escherichia coli pyridoxine 5'-phosphate oxidase complexed with FMN at 1.8 Å resolution". Structure, 2000, 8, 751-762.

M. K. Safo, W. -Z. Yang, L. Corselli, S. Crampton, H. S. Yuan, and R. C. Johnson. "The Regulatory Region of the Fis Protein that Activates Site-Specific DNA Inversion Contains Extended Mobile b-Hairpin Arms". EMBO J. 1997, 16 6860-6873.

M. K. Safo, M. J. M. Nesset, F. A. Walker, P. G. Debrunner, and W. R. Scheidt. "Models of the Cytochromes. Axial Ligand Orientation and Complex Stability in Iron(II) Porphyrinates: The Case of the Non-Interacting dB Orbitals". Journal of the American Chemical Society. 1997, 119 9438-9448.

K. -F. Chak, M. K. Safo, W. -Y. Ku, H. S. -Y Hsieh, and H. S. Yuan. "The Crystal Structure of the ImmE7 Protein Suggests a Possible Colicin Colicin-Interacting Surface". Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 6437-6442.

D. J. Abraham, M. K. Safo, T. Boyiri, R. E. Danso-Danquah, J. Kister, and C. Poyart "How Allosteric Effectors Can Bind to the Same Protein Residue and Produce Opposite Shifts in the Allosteric Equilibrium". Biochemistry, 1995, 34, 15006-15020.

T. Boyiri, M. K. Safo, R. E. Danso-Danquah, J. Kister, C. Poyart, and D. J. Abraham. "Bis-Aldehyde Allosteric Effectors as Molecular Ratchets and Probes". Biochemistry, 1995, 34, 15021-15036.

M. K. Safo, F. A. Walker, P. G. Debrunner, and W. R. Scheidt. "Axial Ligand Orientation in Iron(III) Porphyrinates. Effect of Axial pi-Acceptors. Characterization of the Low-Spin Complex [Fe(TPP)(4-CNPy)2]ClO4". Journal of the American Chemical Society, 1994, 116, 7760-7770.

W. R. Scheidt, H. Song, K. J. Haller, M. K. Safo, R. D. Orosz, C. A. Reed, P. G. Debrunner, and C. E. Schulz. "Characterization of Fe(OEP) pi-Cation Radicals". Inorganic Chemistry, 1992, 31, 939-941.

W. R. Scheidt, B. Cheng, M. K. Safo, F. Cukiernik, J. C. Marchon, and P. G. Debrunner. "New Class of Bridged Diiron(III) Complexes with a Single Hydroxo Bridge. The Preparation and Structure of (u-Hydroxo)bis-((octaethylporphinato)iron(III)) Perchlorate". Journal of the American Chemical Society, 1992, 114, 4420-4421.

M. K. Safo, G. P. Gupta, T. Watson, U. Simonis, F. A. Walker, and W. R. Scheidt. "Models of the Cytochromes b. Low-Spin Bis-Ligated (porphinato)iron(III) Complexes with 'Unusual' Molecular Structures and NMR, EPR, and Mossbauer Spectra". Journal of the American Chemical Society, 1992, 114, 7066-7075.

M. K. Safo, G. P. Gupta, F. A. Walker, and W. R. Scheidt. "Models of the Cytochromes b. Attempts to Control Axial Ligand Orientation with a 'Hindered' Porphyrin System". Journal of the American Chemical Society, 1991, 113, 5497-5510.

M. K. Safo, W. R. Scheidt, and G. P. Gupta. "Axial Ligand Orientation in Iron(II) Porphyrinates. Preparation and Characterization of Low-Spin Bis(imidazole)(tetraphenylporphinato)iron(II) Complexes". Inorganic Chemistry, 1990, 29, 626-633.