Michael Klemba
- Director of Biochemistry Study Abroad Programs
- Research area(s): Biochemistry and Drug Discovery of Malaria
Education
Ph.D., Molecular Biophysics and Biochemistry, Yale University, 1996
B.S., Biology and Chemistry, University of Waterloo, 1990
Experience
- 2011 – present: Associate Professor, Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg
- 2005 – 2011: Assistant Professor, Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg
Courses Taught
BCHM 3114: Biochemistry for Biotechnology and Life Sciences
BCHM 4784: Applications in Molecular Life Sciences
BCHM 5784G: Advanced Applications in Molecular Life Sciences
Other Teaching and Advising
Mentor for undergraduate research (e.g., BCHM 4994)
Mentor for doctoral students in the Biochemistry graduate program
Program Focus
Malaria is one of the most devastating infectious diseases in the world today. The objective of my research is to understand how the human malaria parasite Plasmodium falciparum thrives in its host red blood cell. We employ biochemical and cell biological approaches to study:
- Identification of the target of mefloquine in the malaria parasite
- Fatty acid uptake and lipid metabolism by the malaria parasite
- Endocytosis and catabolism of erythrocyte hemoglobin by the parasite
- Lipid catabolism and utilization of host lipid species for fatty acid scavenging
- Protein sorting and trafficking to the parasite’s vacuole and specialized apical secretory organelles
- Mechanisms of action of anti-malarial compounds
PEER-REVIEWED PUBLICATIONS (since faculty appointment)
Dapper, C, Liu, J & Klemba, M (2022) Leveraging a fluorescent fatty acid probe to discover cell-permeable inhibitors of Plasmodium falciparum glycerolipid synthesis. Microbiology Spectrum 10 e0245622.
Ding, S, Fike, KR, Klemba, M & Carlier, PR (2020) In vitro and in vivo evaluation of the antimalarial MMV665831 and structural analogs. Bioorganic & Medicinal Chemistry Letters 30 127348.
Elahi, R, Ray, WK, Dapper, C, Dalal, S, Helm, RF & Klemba, M (2019) Functional annotation of serine hydrolases in the asexual erythrocytic stage of Plasmodium falciparum. Scientific Reports 9 17532.
Elahi, R, Dapper, C & Klemba M (2019) Internalization of erythrocyte acylpeptide hydrolase is required for asexual replication of Plasmodium falciparum. mSphere 8 e00077-19.
Lee, AH, Dhingra, SK, Lewis, IA, Singh, MK, Siriwardana, A, Dalal, S, Rubiano, K, Klein, MS, Baska, KS, Krishna, S, Klemba, M, Roepe, PD, Llinás, M, Garcia, CRS & Fidock DA (2018) Evidence for regulation of hemoglobin metabolism and intracellular ionic flux by the Plasmodium falciparum chloroquine resistance transporter. Scientific Reports 8 13578.
Rosati, M, Dalal, S, & Klemba, M (2017) Two cap residues in the S1 subsite of a Plasmodium falciparum M1-family aminopeptidase promote broad specificity and enhance catalytic activity. Molecular and Biochemal Parasitology 217 7-12.
Ghavami, M, Dapper, CH, Dalal, S, Holzschneider, K, Klemba, M & Carlier PR (2016) Parallel inhibition of amino acid efflux and growth of erythrocytic Plasmodium falciparum by mefloquine and non-piperidine analogs: implication for the mechanism of antimalarial action. Bioorganic & Medicinal Chemistry Letters, 26 4846-50.
Suárez-Cortes, P, Sharma, V, Bertuccini, L, Costa, G, Bannerman, NL, Sannella, AR, Williamson, K, Klemba, M, Levashina, EA, Lasonder, E & Alano P (2016) Comparative proteomics and functional analysis reveal a role of P. falciparum osmiophilic bodies in malaria parasite transmission. Molecular and Cellular Proteomics, 15 3242-55.
Dalal, S & Klemba, M (2015) Amino acid efflux by asexual blood-stage Plasmodium falciparum and its utility in interrogating the kinetics of hemoglobin endocytosis and catabolism in vivo. Molecular and Biochemical Parasitology, 201 116-22.
Wiley JD, Merino EF, Krai PM, McLean KJ, Tripathi AK, Vega-Rodríguez J, Jacobs-Lorena M, Klemba M, Cassera MB (2015) Isoprenoid precursor biosynthesis is the essential metabolic role of the apicoplast during gametocytogenesis in Plasmodium falciparum. Eukaryotic Cell, 14 128-39.
Krai, P, Dalal, S & Klemba, M (2014) Evidence for a Golgi-to-endosome protein sorting pathway in Plasmodium falciparum. PLoS One 9 e89771.
Poreba M, Mihelic M, Krai P, Rajkovic J, Krezel A, Pawelczak M, Klemba M, Turk D, Turk B, Latajka R & Drag M (2014) Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C. Amino Acids 46 931-43.
Dalal, S, Ragheb, RT, Schubot, FD & Klemba, M (2013) A naturally variable residue in the S1 subsite of M1 family aminopeptidases modulates catalytic properties and promotes functional specialization. Journal of Biological Chemistry 288 26004-12.
Denloye, T, Dalal, S & Klemba, M (2012) Characterization of a glycerophosphodiesterase with an unusual tripartite distribution and an important role in the asexual blood stages of Plasmodium falciparum. Molecular and Biochemical Parasitology 186 29-37
Dalal, S, Ragheb, DRT & Klemba, M (2012) Engagement of the S1, S1’ and S2’ subsites drives efficient catalysis of peptide bond hydrolysis by the M1-family aminopeptidase from Plasmodium falciparum. Molecular and Biochemical Parasitology 183 70-77
Ragheb, D, Dalal, S, Bompiani, KM, Ray, WK & Klemba, M (2011) Distribution and biochemical properties of an M1-family aminopeptidase in Plasmodium falciparum indicate a role in vacuolar hemoglobin catabolism. Journal of Biological Chemistry 286 27255-65
Velmourougane, G, Harbut, M, Dalal, S, McGowan, S, Oellig, CA, Whisstock, JC, Klemba, M & Greenbaum, DC (2011). Synthesis of new (-)-Bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase. Journal of Medicinal Chemistry, 54 1655-66
Wang, F, Krai, P, Deu, E, Bibb, B, Lauritzen, C, Pedersen J, Bogyo M & Klemba, M (2011) Biochemical characterization of Plasmodium falciparum dipeptidyl aminopeptidase I. Molecular and Biochemical Parasitology, 175 10-20
Deu, E, Yang, Z, Wang, F, Klemba, M & Bogyo, M (2010) Use of activity-based probes to develop high throughput screening assays that can be performed in complex cell extracts. PLoS One 5 e11985
Ragheb, D, Bompiani, K, Dalal, S & Klemba, M (2009) Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in the food vacuole and cytosol. Journal of Biological Chemistry 284 24806-15
Dalal, S, & Klemba, M (2007) Roles for two aminopeptidases in vacuolar hemoglobin catabolism in Plasmodium falciparum. Journal of Biological Chemistry 282 35978-87