Dave L Roman

Dave L Roman

, PhD
  • Associate Professor, Department of Pharmaceutical Sciences and Experimental Therapeutics / Division of Medicinal and Natural Products Chemistry

Office

S327 PHAR
Medicinal & Natural Products Chemistry, 115 S Grand Av
Iowa City, Iowa 52242

Phone

(319) 335-6920

Dave L Roman Headlines

Research Narrative

Research in the Roman Lab focuses on the role of Regulator of G Protein Signaling (RGS) proteins in normal cellular signal transduction as well as in disease states, such as cancer. Primarily, we are interested in the discovery and development of small molecule interventions, which we call "pre-therapeutic' agents that have potential to become drugs. We are heavily interested and invested in high throughput screening to accomplish our research goals. To do so, we implement the cutting-edge technologies including dynamic mass redistribution, AlphaScreen and fluorometric, genetically encoded biosensors for interrogating RGS protein activity in cells.

One of our projects, currently supported by the National Cancer Institute, is focused on identifying small molecule inhibitors of RGS17. RGS17 is a protein upregulated in both prostate and familial lung cancers. Studies have shown that knockdown of RGS17 in these tumor types causes both tumor shrinkage and a reduction of metastatic potential of those cells. Our prime objective is to recapitulate that phenotype using chemical tools discovered through the use of High Throughput Screening (HTS). In HTS, we screen tens of thousands of diverse small molecules to identify those that inhibit RGS17s function in cancer cells. We utilized highly sophistocated robotics (check out the UI HTS facility page) to perform these screens. After identification of novel inhibitors, they can be optimized for potency, specificity and safety using medicinal chemistry techniques. On this project, we collaborate with Dr. Zhendong Jin, also in the MNPC division at Iowa, who brings his significant synthetic medicinal chemistry expertise to bear on this project. We also collaborate with Dr. Michael Henry, UI Dept. of Molecular Physiology and Biophysics (and Deputy Director of Basic Research for the Cancer Center), who is an expert in prostate cancer.

Curriculum vitae

Education
BS, Chemistry & Biological Sciences, Quincy University, Quincy, IL, 1998
PhD, Medicinal Chemistry & Molecular Pharmacology, Purdue University School of Pharmacy, 2004

Professional Experience
2004 - 2008, Postdoctoral Fellow, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan
2008 - 2014, Assistant Professor of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa
2014 - present, Associate Professor of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa

Awards
ASPET Board of Publications Trustees Travel Award, 2007
ASPET Molecular Pharmacology Young Investigator Award Finalist, 2005
University of Michigan Biomedical Research Council Fellowship, 2004
ASPET Graduate Student Travel Award for Experimental Biology, 2003
Quincy University Senior Chemistry Award, 1998
ACS Mark Twain Section, Outstanding Achievement Award, 1998
Elected to Kappa Gamma Pi National Honor Society, 1997
Phi Eta Sigma National Honor Society, 1995
Quincy University Organic Chemistry Award, 1995
Quincy University Scholarship, 1994-1998
Moorman Manufacturing Science Scholarship, 1995-1998

Research
Dr. Roman's research interests are High Throughput Screening, the development of Regulators of G Protein Signaling (RGS) Proteins as drug targets, and the use of Flow Cytometry for studying protein-protein interactions.

Representative Publications
Bodle CR, Mackie DI, Roman DL. RGS17: an emerging therapeutic target for lung and prostate cancers. Future Med Chem. 2013, 5(9):995-1007.

Monroy CA, Mackie DI, Roman DL. A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation. PLoS One. 2013, 8(4):e62247.

Zhang X, Hagen J, Muniz VP, Smith T, Coombs GS, Eischen CM, Mackie DI, Roman DL, Van Rheeden R, Darbro B, Tompkins VS, Quelle DE. RABL6A, a novel RAB-like protein, controls centrosome amplification and chromosome instability in primary fibroblasts. PLoS One. 2013, 8(11):e80228.

Monroy CA, Doorn JA, Roman DL. Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-hydroxy-2-nonenal. Chem Res Toxicol. 2013, 26(12):1832-9.

Vermeer LM, Higgins CA, Roman DL, Doorn JA. Real-time monitoring of tyrosine hydroxylase activity using a plate reader assay. Anal Biochem. 2013, 432(1):11-5.

Higgins CA, Vermeer LM, Doorn JA, Roman DL. Expression and purification of recombinant human tyrosine hydroxylase as a fusion protein in Escherichia coli. Protein Expr Purif. 2012, 84(2):219-23.

Roman DL, Traynor JR. Regulators of G protein signaling (RGS) proteins as drug targets: modulating G-protein-coupled receptor (GPCR) signal transduction. J Med Chem. 2011, 54(21):7433-40.

Mackie, DI, Roman, DL. Development of a novel high-throughput screen and identification of small-molecule inhibitors of the Gα-RGS17 protein-protein interaction using AlphaScreen. J Biomol Screen. 2011, 16(8):869-77.

Blazer LL, Roman DL, Chung A, Larsen MJ, Greedy BM, Husbands SM, and Neubig RR. Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Mol Pharmacol. 2010, 78(3):524-33.

Roman DL, Blazer LL, Monroy CA, Neubig RR. Allosteric inhibition of the regulator of G protein signaling-Galpha protein-protein interaction by CCG-4986. Mol Pharmacol. 2010, 78(3):360-5.

Blazer LL, Roman DL, Muxlow MR, and Neubig RR. Use of flow cytometric methods to quantify protein-protein interactions. Current protocols in cytometry [1934-9297] Blazer, 2010 Chapter 13 pp. 13.11.1 - 13.11.15

Talbot JN, Roman DL, Clark MJ, Roof RA, Tesmer JJ, Neubig RR, Traynor JR. Differential modulation of mu-opioid receptor signaling to adenylyl cyclase by regulators of G protein signaling proteins 4 or 8 and 7 in permeabilised C6 cells is Galpha subtype dependent. Journal of Neurochemistry. 2010, 112(4):1026-34.

Roman, DL. Identification of Ligands Targeting RGS Proteins: High-Throughput Screening and Therapeutic Potential. In Rory A. Fisher, editor: Progress in Molecular Biology and Translational Science, Vol. 86, Burlington: Academic Press, 2009, pp. 335-356.

Roof RA, Roman DL, Clements ST, Sobczyk-Kojiro K, Blazer LL, Ota S, Mosberg HI, Neubig RR. A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen. BMC Pharmacol. 2009, 9:(9), PMCID: PMC2700083.

Roman DL, Ota S, Neubig RR. Polyplexed flow cytometry protein interaction assay: a novel high-throughput screening paradigm for RGS protein inhibitors. J Biomol Screen. 2009, 14(6):610-619.

Pei J, Dishinger JF, Roman DL, Rungwanitcha C, Neubig RR, Kennedy RT. Microfabricated channel array electrophoresis for characterization and screening of enzymes using RGS-G protein interactions as a model system. Anal Chem. 2008 Jul 1;80(13):5225-31.

Shankaranarayanan A, Thal DM, Tesmer VM, Roman DL, Neubig RR, Kozasa T, Tesmer JJ. Assembly of High Order G alpha q-Effector Complexes with RGS Proteins. J Biol Chem. 2008 Dec 12;283(50):34923-34.

Roof RA, Sobczyk-Kojiro K, Turbiak AJ, Roman DL, Pogozheva ID, Blazer LL, Neubig RR, Mosberg HI. Novel Peptide Ligands of RGS4 from a Focused One-Bead, One-Compound Library. Chem Biol Drug Des. 2008, 72(2):111-19.

Bernsteel DJ, Roman DL, Neubig RR. In vitro protein kinase activity measurement by flow cytometry. Analytical Biochemistry, Anal Biochem. 2008 Dec 15;383(2):180-5.

Roman DL, Talbot JN, Roof RA, Sunahara RK, Traynor JR, Neubig RR. Identification of small molecule inhibitors of Regulator of G-protein Signaling 4 (RGS4) using a high throughput flow cytometry protein interaction assay (FCPIA). Mol Pharmacol. 2007, 71,1 169-175

Roof RA, Jin Y, Roman DL, Sunahara RK, Ishii M, Mosberg HI, Neubig RR. Mechanism of action and structural requirements of constrained peptide inhibitors of RGS proteins. Chemical Biology & Drug Design, 2006, 67, 266-274.

Roman DL, Walline CC, Rodriguez GJ, Barker EL. Interactions of antidepressants with the serotonin transporter: a contemporary molecular analysis. Eur J Pharmacol. 2003 Oct 31;479(1-3):53-63.

Roman DL, Saldana SN, Nichols DE, Carroll FI, Barker EL. Distinct molecular recognition of psychostimulants by human and Drosophila serotonin transporters. The Journal of Pharmacology and Experimental Therapeutics, 2004, 308, 679-687.