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Michael Klemba

Associate Professor
  • Director of Biochemistry Study Abroad Programs
Michael Klemba
306 Engel Hall

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 5304: Enzymology

BCHM 5224: Protein Structure and Function

Other Teaching and Advising

  • Undergraduate 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:

  • 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

Current Projects

Discovery of anti-malarial compounds that target the cytostomal endocytic pathway”- funded by the Bill and Melinda Gates Foundation. The objective of this project is to screen 400 validated anti-malarial compounds (the “Malaria Box”) to identify novel inhibitors of host hemoglobin uptake through the ctyostomal endocytic pathway.

“Roles of Two Aminopeptidases in Peptide Catabolism in the Malaria Parasite”- funded by the National Institutes of Health. The goals of this project are to define the biochemical and structural properties of two vacuolar aminopeptidases that participate in hemoglobin catabolism in the human malaria parasite Plasmodium falciparum.

PEER-REVIEWED PUBLICATIONS (since faculty appointment)

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