Department of Structural Biology Jacobs School of Medicine And Biomedical Sciences 955 Main Street Buffalo, New York 14203-1121 Phone: 716-829-3698 mgm22@buffalo.edu
The Malkowski Laboratory is focused on understanding the structure and function of integral membrane enzymes involved in the conversion of lipid precursors into potent bioactive signaling molecules. We utilize a myriad of methods and techniques to characterize these enzymes, including X-ray crystallography, electron spin resonance spectroscopy, protein chemistry, biochemistry, molecular biology, cell biology, and kinetics.
Education and Training:
PhD, Biochemistry, Wayne State University (1997)
BS, Chemistry, University of Detroit, Magna Cum Laude (1991)
Employment:
Professor, Structural Biology, University of Buffalo Jacobs School of Medicine & Biomedical Sciences (2014-present)
Principal Research Scientist, Hauptman-Woodward Medical Research Institute (2012–2017)
Research Assistant Professor, Structural Biology, University of Buffalo Jacobs School of Medicine & Biomedical Sciences (2002–2014)
Senior Research Scientist, Hauptman-Woodward Medical Research Institute (2007–2012)
Research Scientist, Hauptman-Woodward Medical Research Institute (2001–2007)
NIH Postdoctoral Fellow, Biochemistry, Michigan State University (1997–2001)
Awards and Honors:
Eicosanoid Research Foundation Young Investigator Award (2011)
Arthritis Investigator Award, Arthritis Foundation (2005)
NRSA Individual Postdoctoral Fellowship, National Institutes of Health (1999)
NIH Predoctoral Training Fellowship, Wayne State University (1993)
Merck Index Award, Outstanding Chemistry Student, University of Detroit (1991)
Presidential Scholarship, University of Detroit, Detroit, MI (1987)
Research Expertise:
Fatty Acid Metabolism: Interested in membrane associated enzymes involved in the (di)oxygenation of fatty acid substrates. Current systems being studied in the lab include 1) cyclooxygenase-1 and -2 (COX-1 and COX-2); and 2) pathogen-inducible oxygenase (PIOX).
Protein Expression and Purification: Extensive technical expertise in: 1) the expression of prokaryotic and eukaryotic proteins in E. coli, S. cerevisiae, and insect cell expression hosts; 2) purification of soluble and membrane proteins using various modes of column chromatography.
Structural Biology of Membrane Proteins: Expertise in structure-function studies of membrane proteins, including 1) expression in insect cells, E. coli, and S. cerevisiae; 2) detergent solubilization; 3) purification; 4) pre-crystallization screening of protein-detergent complexes; and 5) high-throughput crystallization screening and optimization.
X-ray Crystallography: Expertise in all aspects of structure determination using x-ray crystallographic methods, including: 1) high-throughput crystallization screening and optimization; 2) cryopreservation; 3) in-house and synchrotron data collection; 4) phasing (MIR and MAD); and 5) refinement and model building.
UB 2020 Strategic Strengths:
Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
April 2019–March 2024 Exploring New Virulence Factors of the Oral Spirochete Treponema denticola National Institutes of Health Role: Co-Principal Investigator
September 2017–August 2020 Community Crystallization Resource for Biological Macromolecules National Institutes of Health/NIGMS Role: Principal Investigator
August 2015–July 2019 Structure and Dynamics of Cyclooxygenase Catalysis and Inhibition NIH/NIGMS Role: Principal Investigator
April 2013–March 2017 Characterization of Treponema pallidum Rare Outer Membrane Proteins National Institutes of Health/NIAID Role: Co-Investigator
July 2010–June 2015 Multi-Level Optimization of Membrane Proteins for Crystallography NIGMS Role: Principal Investigator
September 2011–May 2015 Catalysis by Prostaglandin Endoperoxide H Synthases NIGMS Role: Co-Investigator
January 2008–December 2012 T. pallidum Membrane Immunogènes and Anti-Oxidant Defense National Institutes of Health/NIAID Role: Co-Investigator
February 2007–January 2012 Structure Biology of Oxylipin Biosynthesis NIH/NIGMS Role: Principal Investigator
American Society for Biochemistry and Molecular Biology (2009–present)
Presentations:
"New Insights into Cyclooxygenase Catalysis and Inhibition" Seminar Series; University of Connecticut; Department of Molecular Biology and Biochemistry (2016)
"New Perspectives in Cyclooxygenase Structure, Function, and Dynamics" Seminar Series; SUNY at Buffalo; Department of Oral Biology (2014)
"Investigating Cyclooxygenase-2 Catalysis and Inhibition in a Lipid Bilayer" Bioactive Lipids in Cancer, Inflammation, and Related Disease 13th International Conference; Eicosanoid Research Foundation (2013)
"Monotopic Membrane Enzymes: Structural Features that Govern Catalysis at the Membrane Interface" Advanced Photon Source User's Meeting; Argonne National Laboratory (2013)
"Do Plants Have COX? Structural Studies of a Cyclooxygenase-like alpha-dioxygenase from Arabidopsis" ; Hospital for Sick Kids; Department of Molecular and Structural Function (2012)
"Flexibility Drives Substrate Promiscuity in Cyclooxygenase-2" CHESS User's Meeting; Cornell University (2012)
"Insights into the Oxygenation of Substrates by COX-2" ; SUNY-IT; Department of Chemistry (2012)
"Molecular Features that Govern the Oxygenation of Substrates by COX-2" 14th Winter Eicosanoid Conference (2012)
"The Structure of alpha-Dioxygenase: a Case Study in the Use of Detergent Phase Boundaries to Crystallize Membrane Proteins" ; Michigan State University; Department of Biochemistry (2011)
"The Who, What, and Why of Structural Biology" ; University of Detroit-Mercy; Department of Chemistry (2011)
"Substrate Binding to Cyclooxygenase-2: Insight into Specificity and Catalysis" Bioactive Lipids in Cancer, Inflammation, and related Diseases 12th International Conference; Eicosanoid Research Foundation (2011)
"High-Throughput Crystallization Screening for the Structural Biology Community" American Crystallographic Association Annual Meeting; American Crystallographic Association (2011)
"Structural Studies of Fatty Acid Oxygenation by Membrane Bound Enzymes" The Institute for Molecular Diversity and Drug Design 13th Annual Symposium; University of Louisville (2011)
"Using Experimentally Derived Detergent Phase Boundaries to Facilitate Crystallization of Membrane Proteins" 13th International Conference on the Crystallization of Biomolecules (2010)
"Multi-Level Optimization of Membrane Proteins" PSI:Biology Kickoff Meeting; National Institutes of Health; National Institute for General Medical Sciences (2010)
"Just a Phase? Using Experimentally-derived Detergent Phase Boundaries to Facilitate Crystallization of Membrane Proteins" 40th Mid-Atlantic Crystallography Meeting (2010)
"Using Experimentally-Derived Detergent Phase Boundaries to Facilitate Crystallization of Membrane Proteins" ; GlaxoSmithKline (2010)
"Then and Now: Structural Biology of Cyclooxygenase-2" ; Vanderbilt University; Institute of Chemical Biology (2010)
"CHTSB: Technology Development Highlights" Protein Structure Initiative Annual Meeting; National Institutes of Health; National Institute of General Medical Sciences (2009)
"Molecular Determinants Governing Oxylipin Biosynthesis in Fatty Acid Oxygenases" ; Johns Hopkins University; Department of Chemistry (2009)
"Recent Advances in Membrane Protein Crystallization: Determination and Application of Empirically-Derived Detergent Phase Boundaries for Crystallization" 2009 SSRL/LCLS User's Meeting; Stanford University (2009)
"Molecular Determinants Governing Fatty Acid Oxygenation in alpha-dioxygenases" Regulatory Oxylipins: an International Symposium (2009)
"Technology Development Efforts at the Center for High-Throughput Structural Biology" Protein Structure Initiative Annual Meeting; National Institutes of Health; National Institute of General Medical Sciences (2008)
"Using Detergent Phase Boundaries to Crystallize Membrane Proteins" Protein Structure Initiative 7th Bottlenecks Workshop; National Institutes of Health; National Institute of General Medical Sciences (2008)
"Technology Developments at the CHTSB" Protein Structure Initiative Annual Meeting; National Institues of Health; National Institute of General Medical Sciences (2007)
"The Utilization of Detergent Phase Boundary Information for Crystallizing Membrane Proteins" 65th Annual Pittsburgh Diffraction Conference; Pittsburgh Diffraction Society (2007)
"The Center for High-Throughput Structural Biology: Show Me the Bottlenecks" Protein Structure Initiative's 6th Bottlenecks Workshop; National Institutes of Health; National Institute of General Medical Sciences (2007)
"Oxylipin Biosynthesis in Pathogen-Inducible Oxygenase" Biophysics and Structural Biology Retreat; University of Rochester (2007)
"Novel Oxygenations of Arachidonic Acid by Cyclooxygenases" Segal Osteoarthritis Symposium; Northwestern University (2006)
"Technology Development at the Center for High-Throughput Structural Biology" Protein Structure Initiative Annual Meeting; National Institues of Health; National Institute of General Medical Sciences (2006)
"The Center for High-Throughput Structural Biology" Protein Structure Initiative's 5th Bottlenecks Workshop; National Institutes of Health; National Institute of General Medical Sciences (2006)
"Novel Oxygenations of Polyunsaturated Fatty Acids" Upstate New York Structural Biology Day; University of Rochester (2003)
"Fatty Acid Interactions with Cyclooxygenases" ; Roswell Park Cancer Institute; Department of Molecular and Cellular Biophysics (2001)
JSMBS Research Strategic Plan Steering Committee; Member (2017–present)
ZRG1 BCMD-T (01) I;; Panel Member (2016)
BioXFEL Faculty Search Committee; Committee Member (2016–present)
ZRG1 BCMB-D (02) M;; Ad Hoc Reviewer (2016)
MSFB;; Ad Hoc Reviewer (2015)
PPBS Admissions Commitee; Committee Member (2015–2016)
NIH; ZGM1 CBB-0 (EM);; Panel Member (2015)
PPBS Steering Committee Department of Structural Biology representative; Committee Member (2013–present)
ZRG1 BCMB-D (0);; Panel Member (2013)
IGPBS Admissions Assessment Committee Department of Structural Biology representative; Committee Member (2008)
IGPBS Steering Committee Department of Structural Biology representative; Committee Member (2001–2009)
IGPBS Admissions Committee Department of Structural Biology representative; Committee Member (2001–2003)
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Department of Structural Biology Jacobs School of Medicine And Biomedical Sciences 955 Main Street Buffalo, New York 14203-1121 Phone: 716-829-3698 mgm22@buffalo.edu