Skip to Main Content

Ronald S. Kaplan, PhD

Ronald S.  Kaplan, PhD
Executive Vice President for Research, RFUMS; Vice Dean for Research, CMS; Professor

Biochemistry and Molecular Biology Discipline

Center for Proteomics and Molecular Therapeutics

Dr. Ronald S. Kaplan received his B.A. (1973), M.S. (1975), and PhD (1981) in Biology/ Biochemistry from New York University. His doctoral research focused on the characterization of citrate transport in mitochondria from tumor cells. Subsequently, he received postdoctoral training at The Johns Hopkins University School of Medicine from 1980-1986. His research there focused on molecular and functional characterization of the mitochondrial dicarboxylate and phosphate transporters.

Dr. Kaplan joined the faculty of the Department of Pharmacology at the University of South Alabama College of Medicine in 1986 as a tenure-track Assistant Professor. He was promoted to Associate Professor with tenure in 1991 and to Professor in 1996. Dr. Kaplan then joined the faculty of the Department of Biochemistry & Molecular Biology at Rosalind Franklin University of Medicine and Science as a tenured Professor in 1997. He became Vice-Chair of the Department in 2002 and Chair in 2006. In August 2010, Dr. Kaplan assumed responsibilities of the Vice Dean for Research of Chicago Medical School and in July 2011, he stepped down as Department Chair to become the Vice President for Research at the University.

Dr. Kaplan’s research focuses on the structure, function, and regulation of mitochondrial and plasma membrane citrate transport proteins at the molecular level. These transporters are key to the energy metabolism of numerous cell types. He is recognized as an international expert in the field of mitochondrial transporters and has been funded by NIH for over 20 years, as well as by NSF and numerous private granting agencies. In addition to his research efforts, Dr. Kaplan directed the Medical Biochemistry course for 9 years and has served the University community as Chair of the Faculty Compensation Committee and as the faculty representative to the University Board of Trustees.

As the Executive Vice President for Research, Dr. Kaplan provides leadership for the vision, development, implementation, and oversight of research activities throughout the university. As Vice Dean for Research, he provides leadership for research activities within the Chicago Medical School. Dr. Kaplan also continues his research endeavors and teaching responsibilities in the Department of Biochemistry & Molecular Biology.

Research

Dr. Kaplan's research interest is the structure, function, and regulation of mitochondrial anion transport proteins at the molecular and atomic levels. A major focus of this laboratory concerns the mitochondrial citrate transport protein (i.e., CTP) since this carrier occupies a fundamentally important position within hepatic intermediary metabolism. Using an array of biochemical and biophysical we are attempting to:

  • Identify those amino acid residues which comprise the substrate binding site(s) and translocation pathway through the CTP;
  • Identify residues that form the dimer interface.
  • Develop conditions permitting the growth of X-ray quality crystals of the CTP, thereby setting the stage for a high resolution 3-dimensional structure of this metabolically important carrier.

Depiction of elements of the substrate translocation pathway within the homology-modeled structure of the mitochondrial citrate transport protein. This panel depicts a view into the transport pathway from the cytosolic face of the lipid bilayer. Residues within transmembrane domain III that are protected by substrate and thus likely line the pathway are depicted in red, while those that are not protected and face away from the pathway are depicted in blue. Q182 (orange) may sterically block L120 (blue) even though L120 faces the pathway.

Two citrate binding sites within the CTP transport pathway viewed in the plane of the membrane bilayer. Two citrate binding sites, viewed in the plane of the membrane bilayer (i.e., a side view) are presented. The backbone of the CTP is represented as a green ribbon. Important side chains are shown as stick structures, and citrate molecules are shown as space filling structures. Citrate oxygens are red. In site one, the citrate carbons and the directly interacting side chains are magenta; in site two, the citrate carbons and the directly interacting side chains are cyan. The distance between the two sites (measuring at the central carbon atoms of the two citrates) is 9.2 Å. Portions of TMDs I, II, and VI have been cut away for clarity. Black horizontal lines at right indicate the approximate boundaries of the bilayer and the atomic ruler at the left indicates approximate dimensions.

Publications

  • Sun, J., Mayor, J.A., Kotaria, R., Walters, D.E., and Kaplan, R.S. Molecular Characterization of the Plasma Membrane Citrate Transporter. In preparation for submission to J. Biol. Chem. (2020).
  • Nie, R., Stark, S., Symersky, J., Kaplan, R.S., and Lu, M. Structure and function of the divalent anion/Na+ sympter from Vibrio cholera and a humanized variant. Nature Comm. 8:15009 (2017).
  • Aluvila, S., Kotaria, R., Sun, J., Mayor, J.A., Walters, D.E., Harrison, D.H.T., and Kaplan, R.S., The Yeast Mitochondrial Citrate Transport Protein: Molecular Determinants of its Substrate Specificity. J. Biol. Chem. 285:27314-27326 (2010).
  • Sun, J., Aluvila, S., Kotaria, R., Mayor, J.A., Walters, D.E., and Kaplan, R.S., Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis. Mol. Cell. Pharmacol. 2:101-110 (2010).
  • Mayor, J.A., Sun, J., Kotaria, R., Walters, D.E., Oh, K.J., and Kaplan, R.S., Probing the Effect of Transport Inhibitors on the Conformation of the Mitochondrial Ctirate Transport Protein via a Site-Directed Spin Labeling Approach. J. Bioenerg. Biomembr. 42:99-109 (2010).
  • Aluvila, S., Sun, J., Harrison, D.H.T., Walters, D.E., and Kaplan, R.S., Inhibitors of the Mitochondrial Citrate Transport Protein: Validation of the Role of Substrate Binding Residues and Discovery of the First Purely Competitive Inhibitor. Molecular Pharmacology 77:26-34 (2010).
  • Remani, S., Sun, J., Kotaria, R., Mayor, J.A., Brownlee, J.M., Harrison, D.H.T., Walters, D.E., and Kaplan, R.S., The Yeast Mitochondrial Citrate Transport Protein: Identification of the Lysine Residues Responsible for Inhibition Mediated by Pryidoxal 5’-phosphate. J. Bioenerg. Biomembr. 40:577-585 (2008).
  • Kaplan, R.S. and June A. Mayor, Molecular Structure of the Mitochondrial Citrate Transport Protein, In: Advances in Biochemistry in Health and Disease: Mitochondria – The Dynamic Organelle, (Schafer, S.W., and Suleiman, M.-S. Eds.), Springer, New York, pp. 97 - 116 (2007).
  • Ma, C., Remani, S., Sun, J., Kotaria, R., Mayor, J.A., Walters, D.E., and Kaplan, R.S., Identification of the Substrate Binding Sites within the Yeast Mitochondrial Citrate Transport Protein. J. Biol. Chem. 282:17210-17220 (2007).
  • Ma, C., Remani, S., Kotaria, R., Mayor, J.A., Walters, D.E., and Kaplan, R.S., The Mitochondrial Citrate Transport Protein: Evidence for a Steric Interaction Between Glutamine 182 and Leucine 120 and its Relationship to the Substrate Translocation Pathway and Identification of Other Mechanistically Essential Residues. Biochim. Biophys. Acta, 1757:1271-1276 (2006).
  • Ma, C., Kotaria, R., Mayor, J.A., Remani, S., Walters, D.E., and Kaplan, R.S., The Yeast Mitochondrial Citrate Transport Protein: Characterization of Transmembrane Domain III Residue Involvement in Substrate Translocation. J. Biol. Chem., 280: 2331- 2340 (2005).
  • Cascio, M., Mayor, J.A., and Kaplan, R.S., Analysis of the Secondary Structure of the Cys-less Yeast Mitochondrial Citrate Transport Protein and Four Single-Cys Variants by Circular Dichroism. J. Bionerg. and Biomembr. 36: 429-438 (2004).
  • Walters, D.E. and Kaplan, R.S., Homology Modeled Structure of the Yeast Mitochondrial Citrate Transport Protein. Biophys. J. 87: 907-911 (2004).
  • Ma, C. Kotaria, R., Mayor, J.A., Eriks, L.R., Dean, A.M., Walters, D.E., and Kaplan, R.S., The Mitochondrial Citrate Transport Protein: Probing the Secondary Structure of Transmembrane Domain III, Identification of Residues that Likely Comprise a Portion of the Citrate Transport Pathway, and Development of a Model for the Putative TMDIII-TMDIII' Interface, J. Biol. Chem. 279:1533-1540 (2004).
  • Eriks, L.R., Mayor, J.A., and Kaplan, R.S., A Strategy for Identification and Quantification of Detergents Frequently Used in the Purification of Membrane Proteins. Anal. Biochem. 323:234-241 (2003).
  • Kaplan, R.S., Methanethiosulfonate Reagent Accessibility Studies, Cysteine-scanning Mutagenesis, Protein Overexpression, and Functional Reconstitution: A Strategy for Studying the Structure/Function Relationships within the Mitochondrial Citrate Transport Protein. In: Transmembrane Transporters, Quick, M.W., Ed., Wiley-Liss, New Jersey, pp. 143-159 (2002).
  • Kaplan, R.S., Structure and Function of Mitochondrial Anion Transport Proteins, J. Membrane Biol. 179: 165-183 (2001).
  • Walters, D.E., and Kaplan, R.S., Models of the Transmembrane Domains of the Yeast Mitochondrial Citrate Transport Protein. J. Molec. Modeling 6: 587-594 (2000).
  • Kaplan, R.S., Mayor, J.A., Kotaria, R., Walters, D.E., and Mchaourab, H.S., The Yeast Mitochondrial Citrate Transport Protein: Determination of Secondary Structure and Solvent Accessibility of Transmembrane Domain IV Using Site-Directed Spin Labeling. Biochemistry 39: 9157-9163 (2000).
  • Kaplan, R.S., Mayor, J.A., Brauer, D., Kotaria, R., Walters, D.E., and Dean, A.M., The Yeast Mitochondrial Citrate Transport Protein: Probing the Secondary Structure of Transmembrane Domain IV and Identification of Residues that Likely Comprise a Portion of the Citrate Translocation Pathway. J. Biol. Chem. 275: 12009-12016 (2000).
  • Xu, Y., Kakhniashvili, D.A., Gremse, D.A., Wood, D.O., Mayor, J.A., Walters, D.E., and Kaplan, R.S.,  The Yeast Mitochondrial Citrate Transport Protein: Probing the Roles of Cysteines, Arg181, And Arg189 in Transporter Function. J. Biol. Chem. 275: 7117-1724 (2000).
  • Kotaria, R., Mayor, J.A., Walters, D.E., and Kaplan, R.S., Oligomeric State of Wild-type and Cysteine-Less Yeast Mitochondrial Citrate Transport Proteins. J. Bioenerg. Bioemembr. 31: 543-549 (1999).
  • Mayor, J.A., Kakhniashvili, D., Gremse, D.A., Campbell, C., Kramer, R., Schroers, A., and Kaplan, R.S., Bacterial Overexpression of Putative Yeast Mitochondrial Transport Proteins, J. Bioenerg. Biomembr. 29: 541-547 (1997).
  • Kaplan, R.S. and Pedersen, P.L., Sensitive Protein Assay in Presence of High Levels of Lipid. In: Biomembranes: Selected Methods in Enzymology, (Packer, L. and Fleischer, S.), Academic Press, New York, pp. 397-403 (1997).
  • Kakhniashvili, D., Mayor, J.A., Gremse, D.A., Xu, Y., and Kaplan, R.S., Identification of a Novel  Gene Encoding the Yeast Mitochondrial Dicarboxylate Transport Protein via  Overexpression, Purification and Characterization  of its Protein Product, J. Biol. Chem. 272: 4516-4521(1997).
  • Kaplan, R.S., Mayor, J.A., Kakhniashvili, D., and Nelson, D., Deletion of the Nuclear        Gene Encoding the Mitochondrial Citrate Transport Protein From Saccharomyces cerevisiae, Biochem. Biophys. Res. Commun. 226: 657-662 (1996).
  • Kaplan, R.S., Mitochondrial Transport Processes. In: Molecular Biology of Membrane Transport Disorders, (Schultz, S.G., Andreoli, T., Brown, A., Fambrough,  D., Hoffman, J. and Welsh, J. eds.), Plenum, New York, pp. 277-302, (1996).
  • Kaplan, R.S., High-Level Bacterial Expression Of Mitochondrial Transport Proteins.  J. Bioenerg. Biomembr. 28: 41-47 (1996).
  • Gremse, D.A., Dean, B., and Kaplan, R.S., Effect of Pyridoxal 5'-Phosphate On the Function of the Purified Mitochondrial Tricarboxylate Transport Protein. Arch. Biochem. Biophys 316: 215-219 (1995).
  • Kaplan, R.S., Mayor, J.A., Gremse, D.A., and Wood, D.O., High-Level Expression and Characterization of the Mitochondrial Citrate Transport Protein From the Yeast Saccharomyces cerevisiae. J. Biol. Chem. 270: 4108-4114 (1995).
  • Xu, Y., Mayor, J.A., Gremse, D.A., Wood, D.O., and Kaplan, R.S., High-Yield Bacterial Expression, Purification, and Functional Reconstitution of the Tricarboxylate Transport Protein From Rat Liver Mitochondria.  Biochem. Biophys. Res.  Commun. 207: 783-789 (1995).
  • Kaplan, R.S. and Mayor, J.A., The Structure, Function, and Regulation of the Tricarboxylate Transport Protein From Rat Liver Mitochondria, J. Bioenerg. Biomembr. 25: 503-514 (1993).
  • Kaplan, R.S., Mayor, J.A. and Wood, D.O., The Mitochondrial Tricarboxylate Trans- port Protein: cDNA Cloning, Primary Structure, and Comparison With Other Mitochondrial Transport Proteins, J. Biol. Chem. 268: 13682-13690 (1993).
  • Tahiliani, A.G., Keene, T. and Kaplan, R.S., Characterization of the Inhibitor Sensitivity of the Coenzyme A Transport System In Isolated Rat Heart Mitochondria, J. Bioenerg. Biomembr. 24: 635-640 (1992).
  • Kaplan, R.S., Mayor, J.A., Blackwell, R., Wilson, G.L. and Schaffer, S.W., Functional Levels of Mitochondrial Anion Transport Proteins in Non-Insulin-Dependent Diabetes Mellitus.  Molec. Cell. Biochem. 107: 79-86 (1991).
  • Kaplan, R.S., Mayor, J.A., Blackwell, R., Maughon, R.H., and Wilson, G.L., The Effect of Insulin Supplementation on Diabetes-Induced Alterations In The Extractable Levels of Functional Mitochondrial Anion Transport Proteins.  Arch. Biochem. Biophys. 287: 305-311 (1991).
  • Hutson, S.M., Roten, S., Oliveira, D.L. and Kaplan, R.S., Solubilization and Functional Reconstitution of the Mitochondrial Branched Chain -Keto Acid Transporter.  In: Amino Acids:Chemistry, Biology and Medicine, (Lubec, G. and Rosenthal, G.A. eds.), ESCOM Science Publishers B.V., Leidon, The Netherlands, pp. 875-880 (1990).
  • Kaplan, R.S., Mayor, J.A., Johnston, N. and Oliveira, D.L., Purification and Characterization of the Reconstitutively Active Tricarboxylate Transporter From Rat Liver Mitochondria. J. Biol. Chem. 265: 13379-13385 (1990).
  • Kaplan, R.S., Oliveira, D.L. and Wilson, G.L., Streptozotocin-Induced Alterations In The levels of Functional Mitochondrial Anion Transport Proteins,  Arch. Biochem. Biophys 280: 181-191 (1990).
  • Hutson, S.M., Roten, S. and Kaplan, R.S., Solubilization and Functional Reconstitution of the Branched Chain -Keto Acid Transporter from Rat Heart Mitochondria.  Proc. Natl. Acad. Sci. U.S.A. 87: 1028-1031 (1990).
  • Kaplan, R.S., Pratt, R.D. and Pedersen, P.L., Purification and Reconstitution of the Phosphate Transporter From Rat Liver Mitochondria.  Methods Enzymol.173: 732-745 (1989).
  • Kaplan, R.S., Mayor, J.A., Oliveira, D.L. and Johnston, N., Recent Developments In the Extraction, Reconstitution, and Purification of the Mitochondrial Citrate Transporter From Normal and Diabetic Rats.  In: Anion Carriers of Mitochondrial Membranes, (Azzi, A., Nalecz, K.A., Nalecz, M.J. and Wojtczak, L., eds.), pp. 59-69, Springer-Verlag, New York, (1989).
  • Kaplan, R.S. and Pedersen, P.L., Sensitive Protein Assay in the Presence of High Lipid.  Methods Enzymol.172: 393-399  (1989).
  • Kaplan, R.S., Pratt, R.D. and Pedersen, P.L., Purification and Characterization of the Reconstitutively Active Phosphate Transporter From Rat Liver Mitochondria. J. Biol. Chem. 261: 12767-12773  (1986).
  • Kaplan, R.S., Pratt, R.D. and Pedersen, P.L., Rat Liver Mitochondrial Phosphate Carrier: Purification and Reconstitution. In: Fourth European Bioenergetics Conference Short Reports, Vol. 4, ICSU Press, Prague, Czech., p. 298 (1986).
  • Kaplan, R.S., Parlo, R.A. and Coleman, P.S., Measurement of Citrate Transport in Tumor Mitochondria.  Methods Enzymol. 125: 671-691 (1986).
  • Kaplan, R.S. and Pedersen, P.L., Determination of Microgram Quantities of Protein in the Presence of Milligram Levels of Lipid with Amido Black 10B.  Anal. Biochem. 150: 97-104 (1985).
  • Kaplan, R.S. and Pedersen, P.L., Isolation and Reconstitution of the n-Butylmalonate-sensitive Dicarboxylate Transporter from Rat Liver Mitochondria.  J. Biol. Chem. 260: 10293-10298 (1985).
  • Kaplan, R.S., Williams, N., Hullihen, J., McEnery, M., Nakashima, R.A., Paggi, M.G. and Pedersen, P.L., Anion Transport, ATP Synthesis, and ATP Export in Liver Mitochondria - Recent Progress on Molecular Components Catalyzing These Processes.  In: Third European Bioenergetics Conference: EBEC Reports Vol. 3A: pp. 345-348 (1984).
  • Kaplan, R.S. and Pedersen, P.L., Characterization of Phosphate Efflux Pathways in Rat Liver Mitochondria.  Biochem. J. 212: 279-288 (1983).
  • Kaplan, R.S. and Coleman, P.S., The Extent of Mitochondrial F1-ATPase and Adenine       Nucleotide Carrier Activity with -ATP.  Biochim. Biophys. Acta 501: 269-274 (1978).
  • Kaplan, R.S. and Coleman, P.S., Mitochondrial ATPase Activity and AdN Translocation with -ATP as Substrate.  FEBS Lett.63: 179-183 (1976).