BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
Roepe, Paul David
POSITION TITLE
Professor, Dept. Chemistry, Georgetown Univ. eRA COMMONS USER NAME
Professor, Dept. Biochem., Cell. & Mol. Biol. proepe GU Medical Center
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Boston University, Boston, MA
Boston University, Boston, MA
DEGREE
(if applicable)
B.S.
M.S. / Ph.D.
YEAR(s)
05/82
05/97
FIELD OF STUDY
Chemistry
Chemistry (Physical)
A. Personal Statement
The Roepe laboratory endeavors to elucidate mechanisms of resistance to cytotoxic drugs, and to design, synthesize and test new drugs based on that information. Defects in transmembraneous drug transport, ion transport, and cellular drug accumulation contribute to drug resistance, so a major focus of the laboratory is to understand these in molecular terms. Current projects include cloning and expression of antimalarial drug resistance proteins, development of biochemical and chemical biology approaches for studying their function, and design, synthesis and testing of novel antimalarial drugs based on that information. There are intriguing molecular similarities between drug resistance in tumors, certain bacteria and parasites, thus, this work may have broad implications. Our laboratory work is highly interdisciplinary, and involves the use of recombinant
DNA technology, cell biological, immunological and biochemical techniques, synthetic chemistry, and modern biophysical techniques such as single - cell photometry, laser confocal, and spinning disk confocal microscopy.
The PI of the laboratory (Roepe) has purposefully pursued interdisciplinary training and currently maintains multiple appointments in order to better address interdisciplinary issues as they arise, since drug resistance research requires an interdisciplinary approach. The Roepe laboratory takes great pride in long-term collaborative work, and key collaborations with laboratories at the NIH, The Scripps Institute, Walter Reed
Army Institute of Research, Notre Dame University, Case Western Reserve, Columbia University, the Johns
Hopkins University, and at Georgetown have been particularly productive.
B. Positions and Honors
Positions and Employment
8/97 - present Member Lombardi Cancer Center;
8/01, 8/06 - present Assoc., Full Professor Department of Biochemistry and Cellular & Molecular Biology ;
97,00,06 present Assist., Assoc., Full Professor, Chair (08 – 10), Department of Chemistry
Georgetown University
5/90 - 8/97 Assistant Member
Memorial Sloan-Kettering Cancer Center
5/90- 8/97 Assistant Professor Department of Pharmacology
Cornell University Medical College
7/89 - 4/90 Research Associate Howard Hughes Medical Institute
UCLA School of Medicine/Molecular Biology Institute (Sponsor, H.R. Kaback)
8/87 - 7/89 Postdoctoral Fellow Biochemistry
Roche Institute of Molecular Biology (Sponsor, H.R. Kaback)
5/87 - 5/88 Postdoctoral Fellow Physics
Boston University (Sponsor, K.J. Rothschild)
Other Experience and Professional Memberships
NIH College of Reviewers (2009 – present)
Defense Threat Reduction Agency (DTRA) ( JSTO Panel, Bacterial Experimental Therapeutics 2004 - )

National Institutes of Health ( Study Section Member and Vice Chair
“
Private Partnerships”” 2010)
NIAID Product Development Public
National Institutes of Health ( Study Section Member
“Pathogenic Eukaryota” 2004-2006)
National Institutes of Health ( Study Section Member
“Trop. Med. & Parasitol.” 2001-2004)
National Science Foundation ( Panel Member
, “Biosensors A” 2004)
Defense Threat Reduction Agency (DTRA) ( Panel Member, Viral / Toxin Experimental Therapeutics 2004)
Dept. of Defense Joint Military Command ( Panel Chair Review of Malaria Therapeutics Program 2003)
Dept. of Defense PRMRP ( Panel Chair , "Molecular Biology and Cancer Research" 2001)
Dept. of Defense BCI ( Panel Member , "Cell and Tissue Biology" 1993-1994)
National Science Foundation, numerous Ad Hoc review 1993 – present; Molecular Biochemistry,
Macromolecular Biochemistry, Biochemistry of Gene Expression, Molecular Biophysics, etc.
National Institutes of Health, numerous additional Ad Hoc review 1995 – present; LRP, ZRG, Minority representation in sciences, etc.
NASA, Ad Hoc Review 2002 –2003; Cell Science and Tissue Engineering
American Chemical Society, Biophysical Society
Honors
National Institutes of Health CSR College of Reviewers (2010 – present)
Faculty of 1000 (Microbiology) (2007 – present)
Georgetown University Center for Infectious Diseases ( co – Director ; 2004 – present)
Burroughs Wellcome New Initiative Awardee (1999-2004)
Sackler Biomedical Scholar (1990-1997)
Jane Coffin Childs Postdoctoral Fellow (1987-1990)
Biophysical Society Young Investigator Award (1988)
C. Selected Peer-reviewed Publications (Selected from >100 peer-reviewed publications)
Most relevant to the current application
Fidock, D.A., Nomura, T., Talley, A.K., Cooper, R.A., Dzekunov, S.D., Ferdig, M.T., Ursos, L.M.B., Su,
X.-z., Wooton, J.C., Roepe, P.D. & Wellems, T.E. (2000) "Mutations in the Digestive Vacuole Transmembrane
Protein PfCRT and Evidence for Their Role in Chloroquine Resistance" Mol. Cell. 6: 861 - 871. PMID:
11090624
Zhang, H., Howard, E.M. & Roepe, P.D. (2002) “Analysis of the Antimalarial Drug Resistance Protein
PfCRT Expressed in Yeast” J. Biol. Chem.
277: 49767 – 49775. PMID: 12351620
Zhang, H., Paguio, M. & Roepe, P.D. (2004) “The Antimalarial Drug Resistance Protein PfCRT Binds
Chloroquine” Biochemistry 43(26): 8290-8296. PMID: 15222741
Amoah, L., Lekostaj, J. & Roepe, P.D. (2007) “High Level Heterologous Expression of the P. falciparum
P- glycoprotein homologue PfMDR1 and Characterization of ATPase Activity” Biochemistry 46: 6060 - 6073.
PMID: 17469853
Paguio, M., Cabrera, M. & Roepe, P.D. (2 009) “Chloroquine Transport in Plasmodium falciparum II:
Analysis of PfCRT Mediated Drug Transport Using Proteoliposomes and a Fluorescent Chloroquine Probe”
Biochemistry 48: 9482 - 9491. PMID: 19725576
Additional recent publications of importance to the field (in chronological order)
Leed, A. DuBay, K., Ursos, L.M.B., Sears, D., de Dios, A.C., & Roepe, P.D.
(2002) " Solution Structures of Antimalarial Drug / Heme Complexes " Biochemistry 41: 10245 – 10255. PMID: 12162739
De Dios, A.C., Tycko, R., Ursos, L.
M.B. & Roepe, P.D. (2003) “NMR Studies of Chloroquine –
Ferriprotoporphyrin IX Complex” J. Phys Chem .
107: 5821 – 5825.
Howard, E.M. & Roepe, P.D. (2003) “Purified Reconstituted hu MDR 1 Protein Modulates Membrane
Potential” Biochemistry 42(12): 3544 - 3555. PMID: 12653559
Waller, K.L., Muhle, R.A., Ursos, L.M.B., Verdier-Pinard, D., Fujioka, H., Roepe, P.D. & Fidock, D.A.
(2003) “Chloroquine resistance modulated in vitro by expression levels of the Plasmodium falciparum chloroquine resistance transporter (
PfCRT)” J. Biol. Chem.
278: 33593 - 33601. PMID: 12813054

Bennett, T.N., Kosar, A.D., Ursos, L.M.B., Dzekunov, S., Sidhu, A.B.S., Fidock, D.A. & Roepe, P.D.
(2004) “Drug resistance-associated PfCRT mutations confer decreased Plasmodium falciparum digestive vacuolar pH.” Mol. Biochem. Parasitol. 133: 99 – 114. PMID: 14668017
Bennett, T.N., Paguio, M., Gligorijevic, B., Sidieu, C., Kosar, A.D., Davidson, E. & Roepe, P.D. (2004)
“Novel, Rapid and Inexpensive Cell – Based Quantitation of Antimalarial Drug Efficacy”Antimicrobial Agents &
Chemotherapy 48: 1807 - 1810. PMID: 15105139
De Dios, A.C., Cassabianca, L., Kosar, A. & Roepe, P.D. (2004) “Structure of the Amodiaquine – FPIX
µ oxo Dimer Solution Complex at Atomic Resolution” Inorg. Chem.
43 (25): 8078 – 8084. PMID: 15578847
Gligorijevic, B., Bennett, T.N., McAllister, R., Urbach, J & Roepe, P.D. (2006) “Spinning Disk Confocal
Microscopy of Intraerythrocytic Malarial Parasites I: Quantification of Hemozoin Development” Biochemistry 45:
12400-12410. PMID: 17029396
Gligorijevic, B., McAllister, R., Urbach, J & Roepe, P.D. (2006) “Spinning Disk Confocal Microscopy of
Intraerythrocytic Malarial Parasites II: Quantification of Digestive Vacuolar Volume” Biochemistry 45: 12411-
12424. PMID: 17029397
Bennett TN, Patel J, Ferdig MT, Roepe PD. (2007) “Plasmodium falciparum Na+/H+ exchanger activity and quinine resistance.” Mol Biochem Parasitol. 153(1):48-58.PMID: 17353059
Glikoreijevic, B., Purdy, K., Elliot, D.A., Cooper, R.A. & Roepe, P.D. (2008) “Stage Independent
C hloroquine Resistance and Chloroquine Toxicity Revealed via Spinning Disk Confocal Microscopy” Mol.
Biochem. Parasitol. 159: 7 – 23. PMID: 18281110
Lekostaj JK, Amoah LE, Roepe PD. (2008) “A single S1034C mutation confers altered drug sensitivity to
PfMD R1 ATPase activity that is characteristic of the 7G8 isoform.” Mol Biochem Parasitol. 157(1):107-11.
PMID: 18006157
Natarajan, J.K., Alumusa, J., Yearick, K., Ekoue - Kovi, K.A., Casabianca, L.B., de Dios, A., Wolf, C. &
Roepe, P.D. (2008) “4-N, 4-S & 4-O Chloroquine Analogues: Influence of Side Chain Length and Quinolyl
Nitrogen pKa on Activity vs. Chloroquine Resistant Malaria ” J. Med. Chem .
51: 3466 - 3479. PMID: 18512900
Lekostaj, J., Natarajan, J.K., Paguio, M., Wolf, C. & Roepe, P.D. (2008) “Photolabelling of the Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) with a Novel per – Fluoroazido Chloroquine”
Biochemistry . 47(39):10394-406 PMID: 18767816
Casabianca
(2009)
, L.B., Kallgren , J.B., Natarajan , J.K., Alumasa, J.N., Roepe, P.D., Wolf, C., & de Dios, A.C.
“ Antimalarial Drugs and Heme in Detergent Micelles: An NMR Study ”
J. Inorg. Chem.
47(13):6077-
81. PMID: 19223262
Ekoue-Kovi, K., Yearick, K., Iwaniuk, D., Natarajan, J. K., Alumasa, J., de Dios, A. C. , Roepe, P. D. &
Wolf, C. (2009 ) “Synthesis and Antimalarial Activity of New 4 – amino – 7 – Chloroquinolyl amides,
Sulfonamides, Ureas, and Thioureas” Bioorg. Med. Chem. 1;17(1):270-83. PMID: 19041248
Hou, Y. Cao, S. Brodie, P.J., Callmander, M.W., Ratovoson, F., Rakotobe, E., Rasamison, V.E.,
Ratsimbason, M., Alumasa, J.N., Roepe, P.D. & Kingston, D.G.I. (2009) “Antiproliferative and Antimalarial
Anthraquinones of Scutia myrtina from the Madagascar Forest” Bioorg. Med. Chem. 17(7):2871-6. PMID:
19282186
Cabrera, M., Nataraj an, J.K., Paguio, M.F., Wolf, C., Urbach, J. S. & Roepe, P.D. (2009) “Chloroquine
Transport in Plasmodium falciparum I: Influx and Efflux Kinetics for Live Trophozoite Parasites using a Novel
Fluorescent Chloroquine Probe” Biochemistry 48: 9471 - 9481 .
PMID: 19728740
Cabrera M, Paguio MF, Xie C, Roepe PD. (2009) “Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity” Biochemistry. 48(47):11152-4.PMID: 19883122