Ryan Davis, PhD

*** * ****** ********* ***

Davis, CA 95616

Cell: 530-***-****

Email: ad1cjx@r.postjobfree.com

Profile

I have extensive experience as a scientist creating timelines, designing experiments, developing methods, and analyzing data to meet deliverables on a strict timeline. I have managed several different multi-disciplinary projects involving guidance of members on how to carry out experiments and which experiments to carry out. Projects that I managed required me to plan all aspects including timing/scheduling, organizing and coordinating job tasks for each person, organization and analysis of all collected data.

Education

Ph.D in Chemistry University of California, Davis September 2012

Dissertation Title: Use of glycosyl iodides for the stereoselective synthesis of cholesteryl glucosides of Helicobacter pylori and analogues.

Degree containing a Designated Emphasis in Biotechnology

Advisor: Professor Jacquelyn Gervay-Hague, Department of Chemistry

M.S. in Chemistry Illinois State University June 2006

Dissertation Title: The examination and syntheses of a variety of oxadiazinones in hopes to yield a more efficient chiral auxiliary in the progress towards the synthesis of tolterodine.

Advisor: Professor Shawn R. Hitchcock, Department of Chemistry

B.S. in Chemistry (ACS) & Molecular Biology Illinois State University June 2004

Double Major

Postdoctoral Research University of California, Davis March 2013-2018

Mentor Professor Julie Sutcliffe, Department of Internal Medicine, Division of Hematology and Oncology, Department of Biomedical Engineering, Co-director of Center of Genomic and Molecular Imaging, and Director of Radiochemistry Research and Training Facility, University of California, Davis

Assistant Project Scientist/Radiochemist October 2018-Present

Preclinical and Clinical Research

My research has entailed both preclinical and clinical development of diagnostic positron emission tomography (PET) radiopharmacueticals and therapeutic agents based on targeted drug delivery of the oncology biomarker integrin- v 6 and their evaluation and validation. I have also worked on a variety of collaborative projects involving multidisciplinary teams and have led study designs, experimental design and set-up for everything from preclinical mouse studies to clinical production of compounds. I have design synthesis tailored for clinical production, developed QC methods to evaluate each radiopharmaceutical’s acceptance criteria in order to insure they can be injected into humans and that those criteria meet FDA regulations.

Skills

As a trained synthetic organic chemist, I excel in the design, synthesis and characterization of organic molecules, peptides, and carbohydrates with the ability to evaluate compounds both in vitro and in vivo for their respective biological target. I have extensive purification experience and use of a variety of analytical techniques such as: HPLC (NP, RP), GC, MS (EI, ESI, MALDI), NMR, FTIR (IR), polarimeter (optical rotation), and circular dichroism (CD)). My postdoctoral work has provided a strong background in both clinical and preclinical studies for the development of both diagnostic and therapeutic agents.

GMP-Clinical Trials

GMP lab set up

GMP QC method development, implementation, maintenance, suitability checks, calibration and execution

GMP-SOP writing for procedures ranging from: equipment use, equipment calibration, equipment maintenance, equipment functioning testing (system suitability checks), standard and reagent preparations, compliance related SOPs, and QC analysis SOPs of the final radiopharmaceutical products.

GMP QC analysis of a final radiopharmaceutical product prior to clinical use

Monitoring and documentation of environmental monitoring (radiation swipe tests, temperature and humidity, radiation exhaust reports, etc)

Aiding & Facilitating adequate characterization of peptide information for FDA-approval (MS-MALDI-peptide sequencing and Edman Degradation peptide sequencing), peptide quantification associated with toxicology studies.

Produce detail cost analysis for production runs of various radiotracers

General Lab Research & Duties

Screening compounds for a target and lead compound design and optimization

Radiochemistry incorporation of radionuclides for positron emission tomography (PET) manual synthesis or use of robotic manipulator arms for synthesis (Radioisotopes used: Ga-68, F-18, Cu-64, Lu-177)

Radiochemical automated synthesis using automated devices such as ELIXYS Flex/Chem radiosynthesizer®, NEPTIS, GE-Tracer lab (development of synthetic programs and their use for automated radiopharmaceutical production)

Aiding in in vitro experiments by performing the radiosynthesis, metabolite analysis of urine, blood, tumor and stability analysis in serum and autoradiography slicing of tissue.

Radiopharmaceutical and drug therapeutic formulations, dosing, and dispensing.

Experience with in vivo experiments that examine the pharmacokinetic profile of radiolabeled compounds in mice and PET/CT-imaging of radiolabeled molecules in mice.

Whole cell assays to probe target ability and selectivity, ELISA assays for relative affinity, other assays to determine inhibition or effective dose, etc..

General laboratory SOPs writing associated with radiation monitoring, and chemical specific SOPs and use.

Maintaining equipment, rotary evaporators, vacuum pumps, lyophilizer, Agilent GC, and Agilent HPLC.

In charge of waste management, ordering of consumables, gas supplies, and liquid nitrogen.

Peptide Synthesis

Nanoparticle Radiolabeling and characterization (SEM, TEM, Zeta-potential, purification)

Small Molecule Synthesis from precursors, prosthetic groups, linkers, multimeric scaffolds and therapeutic agents

Characterization analysis for lab by ESI-MS and MALDI-TOF-MS and NMR experiments

Predoctoral Resarch University of California, Davis January 2007-February 2013

Synthesis of steroidal glycosides with specific stereochemistry about the anomeric carbon for the study of H. pylori.

Train undergrads, help with inventory, in charge of waste management, order chemicals and solvents, and maintain the lyophilizer and vacuum pumps. Ran low resolution and high-resolution mass spectra samples for the group members.

Quarter Abroad Internship Academia Sinica, Taipei, Taiwan March-June 2012

Lab of Professor Chun-Hung Lin

Synthesized cholesteryl glucosides containing azido linkers

Studied metabolites of cholesteryl glycosides in H. pylori cell cultures

Master Research Illinois State University May 2004-May 2006

Synthesized and used chiral auxiliaries in asymmetric Aldol or conjugate addition reactions.

Undergraduate Research Illinois State University August 2002-May 2004

Synthesized gram quantities of a novel chiral auxiliary based from D-camphor and perform asymmetric Aldol reactions.

Work Experience

Bloomington/Normal Water Reclamation District June 2004-August 2005

Lab Manager Mark Beach

Tested sewage water at various treatment stages to make sure they met EPA standards.

Test required included: suspended solids test, fecal coliform, biological oxygen demand, nitrogen quantification, turbidity (optical density), and pH determination.

Overview of Discoveries

Radiochemical Development and Preclinical/Clinical

FLEX-CHEM radiosynthesizer automated radiolabeling of peptides showed the ability to automate a multistep complicated radiosynthesis process for peptides in a robust, efficient manner, which could be translated to multiple patient dose synthesis for eventual GMP-production.

The OBOC library screening research helped to more rapidly identify lead peptide sequences that would bind to integrin- v 6 while eliminating nonspecific binders simultaneously. The work also illustrated what chemical modifications were tolerated by the lead sequence in order to optimize that peptide’s properties towards a better PET-imaging agent.

Preclinical/Clinical production of [18F] v 6-BP, this work determined the optimal sequence of the peptide and showed we could remove a lysine which may radiolabel in solution to provide mixtures and lower yields. This work also demonstrated the ability to image both primary and metastatic disease in a variety of cancers. The PET-images showed low background uptake in normal tissue with high uptake in cancerous lesions with the ability to image subcentimeter metastasis. The clinical impact of this study is immediate as pretreatment molecular imaging can prevent a patients from undergoing surgery unnecessarily and can help monitor success of treatments for of a broad spectrum of malignancies; furthermore, this peptide may serve as a cancer-specific drug delivery platform for future treatment of metastatic disease.

The x-ray crystal structure of a [18F]FPy-TFP precursor provided evidence that the synthesis efficiently switched counter anions required for successful future 18F-radiolabelings.

Tracking of [64Cu]Cu-nanoparticles in lettuce showed that the size of nanoparticle was important in plant uptake of nanoparticles and that plants could uptake nanoparticles intact.

Solid-phase synthesis, cyclization, and radiolabeling of cRGDyK showed that cyclic-peptide radiotracers could be produced from start to finish on solid support resin in a robust, efficient manner leading to cleaner products that require a single semiprep HPLC purification.

Glycolipid and Carbohydrate Synthesis

The trapping of -glycosyl iodides is possible and they are intermediates that hang around for minutes and can be reacted with directly to form -glycosylated products as the major product not requiring in-situ anomerization.

The synthesis of three unique Helicobacter pylori -cholesteryl phosphatidyl glucosides, provided methods to install a phosphatidyl group at the 6-position on a sugar and characterization showed that the chiral-phosphate underwent pyramidal inversion readily giving two diastereomers as products.

The glycosylation followed by enzymatic acylation showed that this route of production of cholesteryl galactosides and glucosides was more efficient than the reverse acylation followed by glycosylation reaction pathway and could be used with either sugar.

The use of trimethylene oxide reaction with glycosyl iodides could afford methods to create sugars with azide linkers that could be clicked to afford multimeric constructs. This work also showed various cyclic ethers could be reacted with glycosyl idodides.

The production of a fused [3.3.0]-neoglycoside lactone showed an unusual product could be formed as a major product from glucuronic acid.

The chemoenzymatic synthesis of cholesteryl-6-O-tetradecanoyl- -D-glucopyranoside showed that these complicated sugars could be made by first acylation followed by glycosylation.

Chiral Auxiliaries for Asymmetric Synthesis

This work showed that six membered chiral auxiliaries based on norephedrine or amino acids known as oxadiazinones could be used to make chiral drug fragments and the larger steric bulk of the R-group at the 4-position of the chiral auxiliary could enhance the diastereomeric ratio and ultimately the enantiomeric ratio of the chiral drug fragment.

Book Chapters

Davis, R. A.; Ganguly, T.; Hausner, S. H.; Sutcliffe, J. L. “Peptides as Vectors for Radiopharmaceutical Therapy.” In: Bodei, L.; Lewis, J. S.; Zeglis, B. M. (2023). Radiopharmaceutical Therapy. pp. 275-296. Springer, Cham. https://doi.org/10.1007/978-3-031-39005-0.

Davis, R. A.; Hausner, S. H.; Sutcliffe, J. L. “Peptides as Radiopharmaceutical Vectors.” In: Lewis, J. S.; Windhorst, A. D.; Zeglis, B. M. (2019). Radiopharmaceutical Chemistry. pp. 137-162. Springer, Cham. https://doi.org/10.1007/978-3-319-98947-1_1.

Radiochemical Development and Preclinical/Clinical Publications

Davis, R. A.; Ganguly, T.; Harris, R. E.; Hausner, S. H.; Kovacs, L.; Sutcliffe, J. L. “Synthesis and evaluation of a monomethyl auristatin E-integrin v 6 binding peptide-drug conjugate for tumor targeted drug delivery.” J.Med.Chem., 2023, 66(14), 9842-9852.

Ganguly, T.; Bauer, N.; Davis, R. A.; Foster, C. C.; Harris, R. E.; Hausner, S. H.; Roncali, E.; Tang, S. Y.; Sutcliffe, J. L. “Preclinical evaluation of 68Ga- and 177Lu-labeled integrin v 6-targeting radiotheranostic peptides.” J. Nucl. Med., 2023, 64(4), 639-644.

Davis, R. A.; Hausner, S. H.; Harris, R.; Sutcliffe, J. L. “A comparison of Evans blue and 4-(p-iodophenyl)butyryl albumin binding moieties on an integrin v 6 binding peptide.” Pharmaceutics, 2022, 14(4), 745.

Kovacs, L.; Davis, R. A.; Ganguly, T.; Chammas, R.; Sutcliffe, J. L. “Repurposing an atherosclerosis targeting peptide for tumor imaging.” Biomed.Pharmacother., 2022, 145, 112469.

Ganguly, T.; Bauer, N.; Davis, R. A.; Hausner, S. H.; Tang, Y. C.; Sutcliffe, J. L. “Evaluation of copper-64-labeled v 6-targeting peptides: Addition of an albumin binding moiety to improve pharmacokinetics.” Mol. Pharmaceutics, 2021, 18(12), 4437-4447.

Foster, C. C.; Davis, R. A.; Hausner, S. H.; Sutcliffe, J. L. “Alphavbeta6 targeted molecular PET/CT imaging of lung post SARS-CoV-2 infection.” J. Nucl. Med., 2020, 61(12), 1717-1719.

Hausner, S. H.; Bauer, N.; Davis, R. A.; Ganguly, T.; Tang, Y. C.; Sutcliffe, J. L. “The effects of an albumin binding moiety on the targeting and pharmacokinetics of an integrin αvβ6-selective peptide labeled with aluminum [18F]fluoride.” Mol. Imaging Biol., 2020, 22, 1543-1552.

Davis, R. A.; Drake, C.; Ippisch, R. C.; Moore, M.; Sutcliffe, J. L. “Fully automated peptide radiolabeling from [18F]fluoride.” RSC Adv., 2019, 9, 8638-8649.

Tang, Y. C.; Davis, R. A.; Ganguly, T.; Sutcliffe, J. L. “Identification, characterization, and optimization of integrin v -targeting peptides from a one-bead one-compound (OBOC) library: Towards the development of positron emission tomography (PET) imaging agents.” Molecules, 2019, 24, 309.

Hausner, S. H.; Bold, R. J.; Cheuy, L. Y.; Chew, H. K.; Daly, M. E.; Davis, R. A.; Foster, C. C.; Kim, E. J.; Sutcliffe, J. L. “Preclinical development and first-in human imaging of integrin v -binding peptide in metastatic carcinoma.” Clinic. Cancer Res., 2019, 25(4), 1206-1215.

Davis, R. A.; Fettinger, J. C. “Crystal structure of N,N,N- trimethyl-5-((2,3,5,6-tetrafluorophenoxy)carbonyl)pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 6-[18F]-fluoronicotinyl-2,3,5,6-tetrafluorophenylester.” Acta Cryst. C, 2018, C74, 604-607.

Davis, R. A.; Rippner, D. A.; Hausner, S. H.; Parikh, S. J.; McElrone, A. J.; Sutcliffe, J. L. “In vivo tracking of copper-64 radiolabeled nanoparticles in Lactuca sativa.” Environ. Sci. Technol. 2017, 51, 125**-*****.

Davis, R. A.; Lau, K.; Hausner, S. H.; Sutcliffe, J. L. “Solid-phase synthesis and fluorine-18 radiolabeling of cycloRGDyK. Org. Biomol. Chem. 2016, 14, 8659-8663.

Glycolipid and Carbohydrate Synthesis Publications

Davis, R. A.; Fettinger, J. C.; Gervay-Hague, J. Synthesis of cholesteryl- -lactoside via generation and trapping of a stable -lactosyl iodide. Tetrahedron Lett. 2015, 56, 3690-3694.

Nguyen, H. Q.; Davis, R. A.; Gervay-Hague, J. Synthesis and structural characterization of three unique Helicobacter pylori -cholesteryl phosphatidyl glucosides. Angew. Chem. Int. Ed. 2014, 53, 134**-*****.

Davis, R. A.; Fettinger, J. C.; Gervay-Hague, J. Tandem glycosyl iodide glycosylation and regioselective enzymatic acylation affords 6-O-tetradecanoyl- -D-cholesterylglycosides. J. Org. Chem. 2014, 79, 8447-8452.

Hsieh, H.-W.; Davis, R. A.; Hoch, J. A.; Gervay-Hague, J. Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its application to multivalent glycoconjugates. Chem. Eur. J. 2014, 20, 6444-6454.

Schombs, M. W.; Davis, R. A.; Fettinger, J. C.; Gervay-Hague, J. A fused [3.3.0]-neoglycoside lactone derived from glucuronic acid. Acta Crystallographica, C, 2013, 69(9), 1062-1066.

Davis, R. A.; Lin, C.-H.; Gervay-Hague, J., Chemoenzymatic synthesis of cholesteryl-6-O-tetradecanoyl- -D-glucopyranoside: a product of host cholesterol efflux promoted by Helicobacter pylori. Chem. Commun. 2012, 48(72), 9083-9085.

Chiral Auxiliaries for Asymmetric Synthesis Publications

Obe, F. O.; Davis, R. A.; Spurlock, J.; Barnes, M. M. G.; Lindvall, T.; Wendorf, M. S.; Delach, C.; Ferrence, G. M.; Standard, J. M.; Hitchcock, S. R., Asymmetric conjugate addition reactions with chiral oxadiazinones: Unusual conformational properties of the oxadiazinones. Tetrahedron, 2021, 83, 132002.

Edler, K. L.; Kirk, S. E. E.; Davis, R. A.; Hitchcock, S. R.; Ferrence, G. M., (5S)-4-(2,2-Dimethylpropyl)-5-isopropyl-1,3,4-oxadiazinan-2-one. javascript:;Acta Crystallographica E, 2010, E66(12), o3329-o3330.

Hitchcock, S. R.; Davis, R. A.; Richmond, D. M.; Dore, D. D.; Kuschel, S. L.; Vaughn, J. F.; Wolfe, J. A.; Hamaker, C. G.; Casper, D. M.; Dingle, J., Synthesis, asymmetric aldol reactions, and X-ray crystallography of some oxadiazinanone derivatives. Journal of Heterocyclic Chemistry, 2008, 45(5), 1265-1274.

Dore, D. D.; Burgson, B. J.; Davis, R. A.; Hitchcock, S. R., Synthesis, reactivity and conformational stability of an L-phenylalanine derived oxadiazinone. Tetrahedron Asymmetry, 2006, 25(16), 2386-2392.

Squire, M. D.; Davis, R. A.; Chianakas, K. A.; Ferrence, G. M.; Standard, J. M.;

Hitchcock, S. R., Synthesis, X-ray crystallography and computational studies concerning an oxadiazinone derived from D-camphor: a structural limitation of oxadiazinones as chiral auxiliaries. Tetrahedron Asymmetry, 2005, 16(5), 1047-1053.

References

Julie Sutcliffe, PhD

Professor, Biomedical Engineer and Internal Medicine, Department of Internal Medicine/ Hematology and Oncology

Co-Director Center of Genomic and Molecular Imaging

Institute of Regenerative Cures

2921 Stockton Blvd.

University of California

Sacramento, CA 95817

E-mail: ad1cjx@r.postjobfree.com

Office: 916-***-****

Jacquelyn Gervay-Hague, PhD

Professor, Department of Chemistry

One Shields Avenue

University of California, Davis

Davis, CA 95616

E-mail: ad1cjx@r.postjobfree.com

Office: 530-***-****

Shawn R. Hitchcock, PhD

Professor, Department of Chemistry

Julian Hall 214

Campus Box 4160

Illinois State University

Normal, IL 61790

E-mail: ad1cjx@r.postjobfree.com

Office: 309-***-****

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