As principal scientist and group manager for the Center of Integrative Chemical Biology and Drug Discovery, Emily Hull-Ryde plays a key role in bringing drug discovery expertise to UNC through collaborative projects with faculty. She came to the School from GlaxoSmithKline where she spent more than 20 years in assay development, compound profiling and hit-to-lead progression. During her GSK tenure, she assembled and led multidisciplinary program teams for hit-to-lead discovery, participated in program teams for two products now in the clinic and provided due diligence and therapeutic expertise for business development teams, one of which acquired the recently approved biologic, albiglutide (Tanzeum). In addition to her extensive knowledge of the drug-discovery process, she also has considerable expertise in kinases and cell signaling pathways.
Since joining UNC, Hull-Ryde has overseen the creation and inventory of the CICBDD’s Diversity and Kinase Libraries (120,000 and 15,000 members, respectively) and coordinated successful assay development and screening campaigns for more than 12 targets, including 9 kinase targets and 6 cell-based screens.
Differential Susceptibility of the Subendocardium to Injury during Cardiopulmonary Bypass Grafting (CABG)
As a new researcher guided by Dr. James E Lowe, a thoracic surgeon at Duke University, Hull-Ryde developed analytical methods to quantitate the total adenine nucleotide pool in tissue samples. These techniques enabled their discovery that the endocardium is the most susceptible region of the heart to ischemic injury. Their findings helped to support a change in surgical protocol: lower circulating blood temperatures during CABG procedures in order to better protect the endocardium. The following publications are representative of this early stage of her research career:
- Hull-Ryde EA, Cummings RG, Lowe JE, (1983) Improved Method for High Energy Nucleotide Analysis of Canine Cardiac Muscle Using Reversed-Phase High-Performance Liquid Chromatography. Journal of Chromatography B: Biosciences and Applications 275:411-417 PubMed PMID: 6619246 (accepted before April 2008).
- Lowe JE, Cummings RG, Adams DH, Hull-Ryde EA, (1983) Evidence that Ischemic Cell Death Begins in the Subendocardium Independent of Variations in Collateral Flow or Wall Tension. Circulation 68(1):190-202. PubMed PMID: 6851046 (accepted before April 2008).
- Hull-Ryde EA, Lewis WR, Veronee CD, Lowe JE, (1986) Simple Step Gradient Elution of the Major High Energy Compounds and Their Catabolites in Cardiac Muscle Using High-Performance Liquid Chromatography. Journal of Chromatography B: Biosciences and Applications 377:165-174 PubMed PMID: 3711205 (accepted before April 2008).
Drug Discovery Research at Glaxo, GlaxoWellcome and GlaxoSmithKline
Over her 23 years at Glaxo, GlaxoWellcome and GlaxoSmithKline, Hull-Ryde conducted research across a number of therapeutic areas, including cardiovascular, osteoporosis, oncology and metabolic diseases. She gained extensive drug-discovery experience, particularly expertise in assay development, hit-to-lead progression and lead optimization. Early on, she developed numerous cell-based models for testing small molecule modulation of targeted proteins in cells. Later, she had scientific leadership responsibility for multidisciplinary teams charged with progressing compounds to clinical candidates. Notable are a series of publications midway in her GSK career as part of a team charged with finding and characterizing peroxisome proliferator-activated receptor g agonists and antagonists. These are representative of the work that could be published according to policies of Glaxo, then GlaxoWellcome, and later GlaxoSmithKline:
- Henke BR, Blanchard SG, Brackeen MF, Brown KK, Cobb JE, Collins JL, Harrington WW Jr, Hashim MA, Hull-Ryde EA, Kaldor I, Kliewer SA, Lake DH, Leesnitzer LM, Lehmann JM, Lenhard JM, Orband-Miller LA, Miller JF, Mook RA Jr, Noble SA, Oliver W Jr, Parks DJ, Plunket KD, Szewczyk JR, Willson TM, (1998) N-(2-Benzoylphenyl)-L-tyrosine PPARgamma Agonists. 1. Discovery of a Novel Series of Potent Antihyperglycemic and Antihyperlipidemic Agents. J Med Chem 41:5020-36 PubMed PMID: 9836620 (accepted before April 2008).
- Oberfield JL, Collins JL, Holmes CP, Goreham DM, Cooper JP, Cobb JE, Lenhard JM, Hull-Ryde EA, Mohr CP, Blanchard SG, Parks DJ, Moore LB, Lehmann JM, Plunket K, Miller AB, Milburn MV, Kliewer SA, Willson TM, (1999) A Peroxisome Proliferator-Activated Receptor g Ligand Inhibits Adipocyte Differentiation. PNAS 96:6102-6106 PubMed PMID: 10339548; PubMed Central PMCID: PMC26842 (accepted before April 2008).
- Su JS, Winegar DA, Wisely GB, Sigel CS, Hull-Ryde EA, (1999) Use of A PPAR Gamma-Specific Monoclonal Antibody to Demonstrate Thiazolidinediones Induce PPAR Gamma Receptor Expression In Vitro. Hybridoma 18:273-280 PubMed PMID: 10475242 (accepted before April 2008).
- Leesnitzer LM, Parks DJ, Bledsoe RK, Cobb JE, Collins JL, Consler TG, Davis RG, Hull-Ryde EA, Lenhard JM, Patel L, Plunkett KD, Shenk JL, Stimmel JB, Therapontos C, Willson TM, Blanchard SG, (2002) Functional Consequences of Cysteine Modification in the Ligand Binding Sites of Peroxisome Proliferator Activated Receptors by GW9662. Biochemistry 41:6640-50 PubMed PMID: 12022867 (accepted before April 2008)
Please note: substantial proprietary and unpublishable work was performed that has not been disclosed due to GlaxoSmithKline’s policies for public disclosure and publication.
Business Development at GlaxoSmithKline
In later years, Hull-Ryde performed due diligence and provided therapeutic expertise for metabolic disease business development teams, one of which acquired the recently approved biologic, albiglutide/Tanzeum.
Early Stage Academic Drug Discovery at UNC
Since joining the Center for Integrative Chemical Biology and Drug Discovery in 2009, Hull-Ryde has collaborated with numerous labs to develop and validate high throughput screening assays for more than 30 targets and have guided most of the small molecule library screening efforts. Additionally, I have directed ADCP activities for 15 of these, 8 of which are oncology targets. The following publications represent some of my UNC collaborations:
- Korboukh I, Hull-Ryde EA, Rittiner JE, Randhawa AS, Coleman J, Fitzpatrick BJ, Setola V, Janzen WP, Frye SV, Zylka MJ, Jin J. (2012) Orally active adenosine A(1) receptor agonists with antinociceptive effects in mice. J Med Chem. 55:6467-77. PubMed PMID: 22738238. PMCID: PMC3501123
- Lee SK, Cheng N, Hull-Ryde E, Potempa M, Schiffer CA, Janzen W,Swanstrom R. (2013) A Sensitive Assay Using a Native Protein Substrate for Screening HIV-1 Maturation Inhibitors Targeting the Protease Cleavage Site between the Matrix and Capsid. PubMed PMID: 23763575. PMCID: PMC3855639
- Christoph, S, DeRyckere, D, Schlegel, J, Frazer, JK, Batchelor, LA, Trakhimets, AY, Sather, S, Hunter, DM, Cummings, C, Liu, J, Yang, C, Kireev, D, Simpson, C, Norris-Drouin, J, Hull-Ryde, EA, Janzen, WP, Johnson, GL, Wang, X, Frye, SV, Earp, HS, Graham, DK. (2013) UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Molecular Cancer Therapeutics. 12:2367-77. PubMed PMID: 23997116. PMCID: PMC3823742
- Yang B, Ming X, Cao C, Laing B, Yuan A, Porter MA, Hull-Ryde EA, Maddry J, Suto M, Janzen WP, Juliano RL. (2015) High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides. Nucleic Acids Research. 43:1987-96 PubMed PMID: 25662226. PMCID: PMC4344505
Positions and Employment
Gaston Memorial Hospital, Gastonia, N.C.
1978–1982 Emergency Room Technician (part-time during school year, summers)
Duke University, Department of Thoracic Surgery, Durham, N.C.
1982–1983 Research Technician
1983–1985 Senior Research Technician
1985–1986 Research Analyst
GlaxoSmithKline / Glaxo Wellcome / Glaxo, Inc., RTP, N.C.
1986–1987 Assistant Scientist, Department of Cardiovascular Pharmacology
1987–1990 Associate Scientist, Department of Cardiovascular Pharmacology
1990–2000 Research Scientist, Department of Cellular and Molecular Pharmacology
2000–2002 Senior Scientist, Metabolic Diseases Center for Expertise in Drug Discovery
2002–2008 Investigator, Metabolic Diseases Center for Expertise in Drug Discovery
University of North Carolina at Chapel Hill, N.C.
2009–2011 Research Operations Manager, Assay Development and Compound Profiling (ADCP), Center for Integrative Chemical Biology and Drug Discovery, Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy
2011–Current Principal Scientist and Group Manager, ADCP, CICBDD, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy
- Silver Research Awards (2), GlaxoSmithKline, Inc. 2002-2007
- Graduate of UNC’s University Leadership Education and Development program (ULEAD) that aims to ‘develop highly skilled and motivated leaders to meet the challenges of the University’s changing environment’. Dec, 2014
- Most Recent Invited Presentation: ‘The Role of Academic Drug Discovery in De-Risking Public Data Mining’, Society for Laboratory Automation and Screening (SLAS). Feb, 2015
Ongoing Research Support
Tier 2 Eshelman Institute for Innovation
Hull-Ryde, Emily (PI)
Controlling the Mucus that Kills Pulmonary Patients
50 million Americans suffer from asthma, chronic obstructive pulmonary disease, and cystic fibrosis. A hallmark of these diseases is excess thick and sticky mucus that can lead to ‘plugging’ of airways and increased morbidity and mortality. Current therapies are not effective in reducing airway mucus overproduction. Our work will lay the foundation for developing novel inhibitors of a protein whose role in airway mucus overproduction was discovered recently at UNC.
R21 AI 111667, NIH
Braunstein, Miriam (PI)
Targeting SecA1 of Mycobacterium tuberculosis for Novel Drug Development
With the rise in drug resistant Mycobacterium tuberculosis (Mtb) strains, the need to develop new drugs for tuberculosis is greater than ever. The research in this proposal will assess the potential of targeting a novel pathway for Mtb drug development: the Mtb Sec export pathway. More specifically, we will investigate the potential of targeting the SecA1 component of the pathway. Because SecA proteins are conserved throughout bacteria, the results of this study may also aid efforts to develop new drugs for other bacterial pathogens.
R01 GM 105883_01, NIH
Vaziri, Cyrus (PI)
Targeting the TLS DNA Damage Tolerance Pathway for Cancer Therapy.
We propose to develop small molecules that inhibit an interaction between the Trans Lesion Synthesis proteins DNA Polymerase eta (Polη) and PCNA that is crucial for DNA damage tolerance and resistance to chemotherapies.
K08 HL 111205-03
Coghill, James (PI)
Attenuating graft-versus-host disease by inhibiting CC-chemokine receptor 7
The primary goal of this grant is to support the development and execution of a high throughput screen against CCR7 for GVHD.
Completed Research Support
R01 AI 099969-01, NIH
Braunstein, Miriam (PI)
Developing High-Throughput Assays for M. tuberculosis Tat Pathway Inhibitors
With the emergence of multiply and extensively drug resistant Mycobacterium tuberculosis strains, the need to develop new drugs for tuberculosis is greater than ever. The twin arginine translocation (Tat) pathway of M. tuberculosis is a good candidate for being a novel drug target. In this project, we will develop automated highthroughput screening assays to use for identifying inhibitors of the twin arginine translocation (Tat) pathway of M. tuberculosis. The compounds identified with these assays will validate the Tat pathway as a novel drug target and serve as leads for development of new tuberculosis drugs.
550KR41219, UNC-CH North Carolina Translational and Clinical Sciences Institute
Hull-Ryde, Emily (PI), Ribeiro, Carla (co-PI)
IRE1β Kinase, a Novel Target for Mucin Production in Cystic Fibrosis, COPD and Asthma Patients
The goal of this project is to 1) clone the kinase domain of IRE1β and 2) develop an assay for IRE1β kinase activity. This assay will be used in subsequent grants to screen for inhibitors of IRE1β that can be utilized as novel therapeutic agents for CF, asthma and COPD airway mucin overproduction.
R21 CA 170332-01, NIH
Janzen, William (PI), Juliano, Rudy (co-PI)
Addressing Undruggable Targets Using Oligonucleotides and Small Molecules (PQ18)
Antisense, siRNA or splice switching oligonucleotides could provide potent tools for manipulating therapeutic targets that are ‘undruggable’ by conventional means. However, the pharmacological effects of oligonucleotides are often blunted because of their poor delivery into the cytosol and nucleus of tissue cells. Here we pursue a novel approach for enhancing oligonucleotide delivery by using small organic molecules that modify the intracellular trafficking of the oligonucleotides and thus enhance their pharmacological actions. If successful this approach would have a major impact on the therapeutic utility of oligonucleotides in cancer.
R21 NS 073052-01A1, NIH
Janzen, William (PI), Swanstrom, Ron (co-PI)
High Throughput Screen For HIV-1 MA/CA Processing Site Inhibitors
A large number of drugs have been developed for HIV-1, but resistance remains a significant problem. Not only that, but resistance to one drug frequently confers some level of cross-resistance to other drugs directed at the same target. Thus there is a continuing need to develop new drug targets for HIV-1. This work will result in the identification of a new class of HIV-1 inhibitors which will set the stage for the screening of larger libraries, and create a paradigm for identifying critical proteolytic processing events in the replication of other viruses to use as new targets.
BOA 29XS126, NCI/SAIC-Frederick, Inc. (Task Order 09)
Frye, Stephen (Lead PI)
Target Validation, Assay Development and Hit Discovery for IDH1-Based Approaches targeting Glioblastoma.
This award funds 1) purifying mutant IDH1 proteins and develop an in vitro enzymatic assay to detect production of α-KG and 2-HG; (2) optimization of a high-throughput assay for discovery of inhibitors of mutant IDH1 2-HG production; and (3) tractable hit discovery as defined in the Statement of Work.
|INSTITUTION AND LOCATION||DEGREE(if applicable)||Completion DateMM/YYYY||FIELD OF STUDY|
|Smith College, Northampton, MA||BA||05/1981||Biochemistry|