Laboratory of Clinical Investigation, National Institute on Aging, Maryland, USA

Talk Title : Ligand Fishing and Bioaffinity Chromatography for Natural Product Screening

Education:

Northeastern University, Boston, MA. 07/1999
PhD. Biomedical Sciences (Medicinal Chemistry/Pharmacology)
Thesis: Synthesis and Characterization of Novel Bifunctional Probes for the Nicotinic Receptors.

Carleton University, Ottawa, Ont. 04/1994
B.Sc with Honors
Thesis: Synthesis of pi-acceptor pi-donor bridging ligands.

 

Brief Chronology of Employment:

11/07-Present: Staff Scientist, National Institute on Aging, NIH

Carry out independent research, supervise, advise and design research for visiting professors, post-doctoral fellows, post-bacculaureate students and undergraduate students in the minority program for NIH. Trained and supervised research-operation of staff of 11 visiting professors (4), post-doctoral fellows (4), technicians (2), and chemists (1). Initiated collaborations with academic institution labs in US and other countries. Served as single point-of-contact to collaborators for ongoing study updates, weekly teleconferences etc. Oversaw the overall operation and administration of the laboratory. Troubleshooted all technical problems and assured the highest level of quality and compliance of the lab with regulations and guidelines. Directed a research team on managing several bioanalytical studies for intramural and extramural collaborations. Assist in planning, organizing and assigning work and advises and guides co-workers for clarification on their projects. Put quality improvements into practice that ensure attainment of objectives.

 Topics

Bioanalytical analysis: of plasma, urine and tissues (humans, mouse, rat and monkey) and cellular matrices using LC-MS/MS with an API-4000 and/or API-5500QTRAP.

Studies included the determination of ketamine and its downstream metabolites in human plasma, rat plasma and rat brains; the determination of Fenoterol and Methoxy Naphthyl Fenoterol in human and rat plasma and rat brains; determination of Resveratrol and its metabolites in mouse, human and monkey plasma and tissues; determination of endogenous levels of homocysteine in plasma samples of rats and rat brains; determination of alfentanil and noralfentanil in human plasma; determination of a series of endocannabinoids in plasma and mouse brains; determination of curcumin and its metabolites in colorectal tissue; determination of cardiolipin in human and monkey skeletal muscle.

Metabolomics: Setup the Biocrates metabolomics system on the API-5500 Qtrap. Metabolites were extracted and concentrations were obtained using the AbsoluteIDQ kit p180 (Biocrates Life Science AG, Austria) following the manufactures protocol. Determined changes between healthy and disease state in plasma samples as well as skeletal muscle.  Developed HPLC-MS/MS assays targeting specific metabolomes.

Proteomics: Oversaw post-doctoral fellows (2), carrying out targeted proteomics for the determination of CB1 and its isoform CB1B in human plasma; determination of GDF11 and GDF8 in human plasma on the API-5500 QTrap. In addition, obtained training on the API 5600 Triple TOF and the Thermo Orbitrap XL. Currently overseeing a chemist and technician carrying out sample analysis on the equipment.

Plate-Based Assays: Developed Plate-Based assays for the CB1, CB2 and GPR55 receptors, measuring the internalization of Win 55212 and CP 55940. Carried out Rubidium efflux studies of the nicotinic receptors for the identification of positive allosteric modulators in order to identify new drug candidates.

CMAC: Creation of Cellular membrane affinity chromatography columns, including human Organic Cation Transporter columns, human organic anion transporter columns (hOAT1 and hOAT2), nicotinic receptor columns (including a3b4, a4b2 and a7), Odorant binding protein column and the P-glycoprotein transporter column. Creation of Nuclear and Mitochondrial membrane affinity chromatography columns.

Ligand Fishing: Developed a novel method with the immobilization of a targeted protein for ligand/protein fishing in complex matrices, including cells and botanical extracts. Identified novel modulators of the SIRT6 protein, CB1/CB2 receptors as well as for the AChE protein using this technique.

9/04-11/07:    Senior Research Scientist, Contractor at NIA/ MedStar Research Institute.

12/01-9/04:    Research Scientist at NIA /Johns Hopkins University

6/01-12/01:    Research Fellow for Dr. Clarke, Department of Oncology, Lombardi Cancer Center, Georgetown University.

9/99-6/01:      Research Fellow for Dr. Wainer, Bioanalytical Center, Georgetown University Medical Center.

4/94-7/99:      Research Assistant, Department of Pharmaceutical Sciences, Northeastern University. Topics: Synthesis of novel bifunctional ligands for muscular and neuronal nicotinic receptors. Containing organoarsenicals and either: biotin, radiolabel, photoaffinity label.

 Teaching

9/00-2007:     Adjunct Faculty, Department of Chemistry, Marymount University

05/03-07/03: Lecturer, Organic Chemistry II, Catonsville College at Baltimore County,    Catonsville, MD. Responsibilities included teaching and supervising a class of 27 students, generating lesson plans and exams.

9/93-4/94:      Teaching Assistant, Department of Chemistry, Carleton University. Responsibilities included the supervision of multiple laboratories and teaching of laboratory techniques in general chemistry.

 

Thesis Committee:

04/15                   Ed Tuan, PhD. Georgetown University, Washington D.C.

Committee member.

09/15                   Kaia-Lisa Habicht, PhD Student. Tallinn University

Co-advisor

Societies:

Rho-Chi Honor Society

American Chemical Society (Inactive)

American Association of Pharmaceutical Sciences (Active)

 

Honors and Other Special Scientific Recognition:

07/16 International Scientific Committee for the 27th International Symposium on PBA

07/15 Secretary of the PBA Steering Committee

07/15 Chaired a session at the PBA 2015 conference

07/15 Scientific Committee of the 26th International Symposium on PBA

10/14 Recipient of Special Act Award from the NIA

11/13 Invited Chair of the Eastern Analytical Symposium Award ceremony.

03/12 Honorary Professor at Jinan University, Guangzhou, China.

10/11 Chaired a session at the PBA 2011 conference

10/10 Recipient of Special Act Award from the NIA

10/09 Recipient of Special Act Award from the NIA

10/08 Recipient of Special Act Award from the NIA

06/08 Chaired a session at the PBA 2008 conference

1/03 Recipient of Johns Hopkins Award for Employee Performance

6/97 Recipient of Parke-Davis Travel Grant Award for September 1997 ACS Meeting.

5/97 Inducted into the Beta-Tau Chapter of the Rho-Chi Honor Society.

4/97  Recipient for Smith-Kline Beecham Award for Excellence in a Podium Presentation.

 

Invited Podium Presentation:

  1. Biology of Healthy Aging Weekly Meeting. 12.19.17. Guest Speaker: Repositioning of Old Drugs: Ketamine.
  2. 24th International Symposium on Electro- and Liquid Phase- Separation Techniques. September 13, 2017. Invited Plenary Lecture: Natural Product Screening for the identification of SIRT6 modulators.
  3. NIA Summer Retreat, June 19, 2017. Reposition of Old Drugs: Ketamine.
  4. 27th International Symposium on Pharmaceutical and Biomedical Analysis 2016 Keynote Lecture: The identification of novel modulators of the SIRT6 protein.
  5. Johns Hopkins University, Clinical Pharmacology Series (04/06/2016) Invited Speaker: Natural Product Screening: SIRT6”
  6. 2015 Eastern Analytical Symposium (EAS) Separation Science Session (11.17.15). Invited Speaker: Natural Product Screening Using Affinity Chromatography.
  7. Jinan University, Guanghzhou, China (10/2015) Invited Speaker: Bioaffinity Chromatography and its application to ligand fishing in botanical extracts.
  8. 26th International Symposium on Pharmaceutical and Biomedical Analysis 2015 (07/06/15) Tbilsi, Georgia. Keynote Lecture: The identification of novel modulators of the SIRT6 protein.
  9. Tallin University (5/7/15) Tallinn, Estonia. Invited Speaker: Bioaffinity Chromatography and its application to ligand fishing.
  10. Tallinn University (5/6/15) Tallinn, Estonia. Invited Speaker: Bioaffinity Chromatography and Drug Screening.
  11. Fujian University of Traditional Chinese Medicine (11/20/2014) Fuzhou, China. Invited Speaker: SIRT6 Protein Immobilization and its application to ligand fishing in botanical matrices.
  12. Fuzhou University (11/18/2014) Fuzhou, China. Invited Speaker: Protein Immobilization and its application to ligand fishing in botanical matrices.
  13. Virginia Commonwealth University (10/7/2014). Invited Speaker: Repositioning of Old Drugs: Ketamine. VCU-AAPS Student Chapter.
  14. University of Maryland School of Medicine (07/31/2014) Downstream Ketamine Metabolites for the Treatment of Depression.
  15. Jinan University, Guanghzhou, China (03/2014) Invited Speaker: The Synthesis and Characterization of SIRT6 Protein Open Tubular Column (SIRT6-OT): Characterization of the Quercetin Binding Site.
  16. 2013 Pittsburgh Conference (PittCon) (03/2013). Invited Speaker: The Synthesis and Characterization of SIRT6 Protein Open Tubular Column (SIRT6-OT): Characterization of the Quercetin Binding Site
  17. Johns Hopkins University, Clinical Pharmacology Special Conference (09/24/2012) Invited Speaker: Bioaffinity Chromatography: Applications and versatility”
  18. Lublin University (06/2012) Lublin, Poland. Invited Speaker: The versatility of Magnetic Beads in Ligand and Protein Fishing.
  19. Jinan University (03/2012) Guangzhou, China. Invited Speaker: Cellular Membrane Affinity Chromatography: Applications and Versatility.
  20. Washington Chromatographic Society, NIST, Rockville, MD. (01/2012) Invited Speaker: Studying Drug-Protein and Protein-Protein Interactions.
  21. PBA 2011 (10/2011) Joao Pessoa, Brazil. Invited Plenary Lecture: Bioaffinity Chromatography: Studying Drug-Protein and Protein-Protein Interactions.
  22. PBA 2008 (06/2008) Gdansk, Poland. Invited Keynote Speaker: Immobilized Proteins on the Surface of Magnetic Beads for Ligand and Protein Fishing. Gdansk, Poland.
  23. HPLC 2008, Baltimore, MD. Immobilized Heat Shock 90 (Hsp90) Magnetic Beads for Ligand and Protein Fishing.
  24. Midwestern University, Glendale, AZ. (2008) Invited Speaker: Characterization and application of the immobilized nicotinic receptor using cellular membrane affinity chromatography .
  25. Recent Developments in Pharmaceutical Analysis (2007) Elba, Italy. Invited Keynote Speaker: Online determination of substrates and inhibitors of the P-glycoprotein and Organic Anion Transporters.
  26. CSPS 10th Annual Symposium, Montreal, Quebec, Canada. (2007) Invited Speaker: Online determination of substrates and inhibitors of the P-glycoprotein and organic cation transporters.
  27. 224th ACS National Meeting, Boston, MA. (2002) Synthesis and Characterization of immobilized neuronal nicotinic receptors and the online screening of nicotinic binding affinities.

 

Other Academic Activities

02/05- Present:      Editor for the Journal of Pharmaceutical and Biomedical Analysis.

Elsevier.

2015-Present:            Editorial Board for the Journal of Pharmaceutical Analysis.

2016-Present          Editorial Board for Gerontology & Geriatrics: Research

2013-Present:            Consulting Editor for Pharmacology Research and Perspectives

2014-Present:            Data Review Committee for BPMS, NIA

2008- Present:        Authorized User from the Division of Radiation Safety

2008-Present:            Technology Transfer Committee

2010-Present:            Chairperson of the NIA IRP Safety Committee

2009- Present:           Reviewer for FARE awards/NIH

2005-Present:         Floor team coordinator for the evacuation protocol at the NIA

2003                    Book Reviewer for Elsevier Science.

2002-Present:            Representative for the NIH Recreation and Welfare at the NIA.

 

Reviewer

2001- Reviewer for Journal of Chromatography Biomedical Sciences and Applications.

2003- Reviewer for Journal of Pharmaceutical and Biomedical Analysis

2005- Reviewer for Analytical Chemistry

2005- Reviewer for Talanta

2005- Reviewer for Journal of Pharmaceutical and Experimental Therapeutics

2006- Reviewer for Analytica Chimica Acta

2007- Reviewer for Journal of Chromatography A

2008- Reviewer for Analytical Biochemistry

2008- Reviewer for Chromatographia

2008- Reviewer for Analytical Bioanalytical Chemistry

2008- Reviewer for Journal of Seperation Science

2009- Reviewer for Analyst

2009- Reviewer for Xenobiotica

2010- Reviewer for Analytical Methods

2010- Reviewer for Free Radical Biology and Medicine

2010- Reviewer for Frontiers Pharmacology

2013- Reviewer for Trends in Analytical Chemistry

2014- Reviewer for PLOS One

2015- Reviewer for Journal of Pharmaceutical Analysis

2015- Reviewer for Molecules

 

Patents

  1. C.Thomas, P.Morris, T.Gould, C.A.Zarate, R.Moaddel, I.W.Wainer, P.Zanos (2016) Crystal forms and methods of synthesis of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine. E-116-2016/0-US-01.
  2. I.W.Wainer, C.A.Zarate, R.Moaddel, P.Zanos, T.Gould, C.Thomas, P.Morris. USE OF THE KETAMINE METABOLITE (2R,6R)-HYDROXYNORKETAMINE IN DEPRESSION. EIR E-053-2016/0-US-01
  3. I.W.Wainer, C.A.Zarate, R.Moaddel, P.Zanos, T.Gould, C.Thomas, P.Morris (2015). Methods of using (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post traumatic stress disorders. EIR E-036-2016/0-US-01/NIH0105US
  4. I.W.Wainer, Ruin Moaddel, C.Zarate (2013) Method for prediction of antidepressant response after the administration of ketamine. EIR submitted.
  5. I.W. Wainer, Ruin Moaddel, Michel Bernier, Michael E. Goldberg, Marc C. Torjman, Donald E. Mager. (2011) The use of (2R, 6R)-Hydroxynorketamine, (S)-dehydronorketamine and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)- ketamine in the treatment of depression and neuropathic pain.  US Application Serial No. 61/547336 filed 10/14/2011; DHHS Reference No.:  E-092-2011/0-US-01.
  6. I.W.Wainer, K. Jozwiak, S. Ravichandran, R. Moaddel, J. R. Collins (2004) Computer based model for identification and characterization of non-competitive inhibitors of nicotinic acetylcholine receptors and related ligand gated ion channel receptors. This is a Continuation-In-Part of U.S. Application No. 10/411,206
  7. I.W.Wainer, R.Moaddel. (2002). Multiple Receptor Chromatograph.US Application No. 60/337,172.
  8. I.W. Wainer, Y. Zhang, F.Beigi, R. Moaddel (2002) Immobilization of Membrane Receptors on HPLC. US 6,387,268.
  9. I.W. Wainer, R.Moaddel, J.F. Cloix, G.Ertem. (2001) Multiple Binding Moiety Chromatography Device, Methods of Making and Methods of Using Same. PCT/US02/39439.

 

Service on Advisory Boards:

 02/14 Added as reviewer of post-doctoral fellow applications for the Research Foundation Flanders – FWO, an independent funding agency that supports fundamental research in all disciplines in Flanders (Belgium).

05/13 Added peer reviewer database for the University of Bologna to evaluate research projects submitted by members of their scientific community (Bologna, Italy)

03/13 Included as korpus recenzentow (reviewers register for grant proposals) of the National Science Center of Poland (www.ncn.gov.pl)

 

 

Grants

2017: Combining FTIR-based Screening with Ligand Fishing Technologies for Facilitated Discovery of Antidiabetic Peptides in Protein Hydrolysates. Norwegian Research Council. Application Number: ES568778

01/01/2017-12/31/2108: (2R,6R)-Hydroxynorketamine for the treatment of major depressive disorder. P.I.Todd Gould. Role: Co-Investigator

2016: 1R01MH107615 – 01A1. Therapeutic Efficacy of Ketamine Metabolites for Depression Treatment.  P.I. Todd Gould.

Role: Co-Investigator: R.Moaddel

2015: Reyhan Westbrook, Ph.D. received Glenn Foundation for Medical Research, in partnership with the American Federation for Aging Research (AFAR). Longitudinal study of serum metabolomics in IL-10 ko mice, in sterile abscess inflammation induced mice, and in control mice. Mentors include Dr. Rafael de Cabo, Dr. Ruin Moaddel, and Dr. Jeremy Walston of the Johns Hopkins Division of Geriatric Medicine and Gerontology.

2015: OAIC grant.  Altered skeletal muscle metabolic pathways in the pathogenesis of sarcopenia. Pingbo Zhang, R.Moaddel, Richard Semba, Luigi Ferrucci.

2013-Present: IACTRS FDA/NIH Collaborative Grant. Screening for active component patterns from Tobacco Smoke Condensates. PI. Irving W.Wainer, Luigi Ferrucci, Co-PIs: R.Moaddel and L. Toll.