Eugene Douglass, Ph.D.

Pharmaceutical and Biomedical Sciences
Assistant Professor

Pharmaceutical and Biomedical Sciences

Education

2008-2014   Ph.D. in Chemical Biology, Yale University

2003-2007 B.A. in Physical Chemistry, Worcester Polytechnic Institute.

Areas of Expertise

Designing small-molecule drugs based on biological mechanisms.

Honors, Awards, and Achievements

Yale University
2015 2010-15 Outstanding Dissertation Award(Northeastern Association of Graduate Schools)
2009 Dox Fellowship in Recognition of Excellence in Academics and Research in Chemistry

Worcester Polytechnic Institute
2008 WPI Institute Fellowship (post-Baccalaureate year of research)
2007 WPI Major Qualifying Project Award
2007 WPI Salisbury Award
2006 ACS Analytical Chemistry Division Undergraduate Award
2006 3rd Place, WPI Graduate Research Achievement Award (as an undergraduate)
2005 Pfizer/Connecticut Business and Industry Association Research Fellowship
2004 Charles O. Thompson Scholar
2004 The General Chemistry Achievement Award

Research Interests

DOCTORAL RESEARCH: Chemical Biology & Immunology (Yale University)

FLUORESCENT SENSORS:
The metabolite methylglyoxyl (MGO) contributes to diabetes symptoms by non-specifically modifying protein side chains. Until recently, studies on MGO have been hampered by the destructive and time consuming (>24 hours) methods used to quantitate MGO concentration. To address these limitations, I designed and tested a panel of fluorescent sensors for MGO that rapidly and accurately quantitated MGO in high throughput and live cell formats.

SMALL MOLECULE IMMUNOTHERAPIES:
Monoclonal antibody (mAb)-based therapies are one of the fastest growing classes of pharmaceutical today. Unfortunately, the median annual cost of these therapies is over $100,000 due to high production and storage costs.  As an alternative, my doctoral laboratory developed small- molecule Antibody-Recruiting Molecules (ARMs)  which “reprogram” pre-existing antibodies to target cancer antigens. I designed, synthesized and tested these molecules and worked in teams to show that ARMs can elicit anti-cancer immune responses (antibody-dependent cellular cytotoxicity and phagocytosis) both in vitro and in vivo. In addition, I derived a mathematical model for bivalent drugs that aided design of ARMs and PROTACs(PROeolysis TArgeting Chimeras) at Yale.

POSTDOC RESEARCH:
Data Science & Clinical Oncology (Columbia University) Genome sequencing technology has laid the foundation for “precision medicine” through the identification of oncogenes and the development of drugs that target oncogenes. Unfortunately, tumor killing is typically mediated by pathways downstream of these drug targets, which often correlate better with drug efficacy in the clinic. To betterunderstand drug mechanism, we have built a drug-perturbed (IC20) RNA sequencing (RNAseq) database.  I oversaw building of this database by coordinating with the Columbia Genome Center and High Throughput Screening center and performed quality control and initial analysis. This database was my main contribution to a three-institute collaboration between Columbia and the Schreiber and Hahn groups at the Broad and Dana-Farber Institutes.

Selected Publications

1. Driscoll, P.F.; Douglass Jr., E.F.; et. al. “Photocurrent generation in noncovalently assembled multilayered thin films” Langmuir, 2008, 24, 5140
2. Douglass Jr., E.F.; et al. “The Effect of Electrode Roughness on the Capacitive Behavior of Self-Assembled Monolayers” Anal. Chem. 2008, 80, 7670.
3. Wang, T.; Douglass Jr., E.F.; et al. “A Fluorescent Turn-On Sensor for Methylglyoxal” J. Am. Chem. Soc. 2013, 135, 12429.
4. Douglass Jr., E.F.; et. al. “A Comprehensive Mathematical Description of Three-Body Equilibria” J. Am. Chem. Soc. 2013, 135, 6092.
5. Jakobsche, C.E.; Parker, C.G.; Tao, R.N.; Kolesnikova, M.D.; Douglass Jr., E.F.; et. al. “Exploring binding & effector functions of human antibodies using synthetic immunomodulator” ACS Chem. Bio. 2013, 8, 2404.
6. Parker, C.G.; Dahlgren, M.K.; Li, D.T.; Douglass Jr., E.F.; et al. “Illuminating gp120–Ligand Recognition through Computationally-Driven Optimization of Antibody-Recruiting Molecules” Chem. Sci. 2014, 5, 2311.
7. McEnaney, P.J.; Fitzgerald, K.J.; Zhang, A. X.; Douglass Jr. E.F.; et al. “Chemically Synthesized Molecules with the Targeting and Effector Functions of Antibodies” J. Am. Chem. Soc. 2014, 136, 18034.
8. Santori, F.R.; Huang, P.; VanDePavert, S.A.; Douglass Jr, E.F.; et al. “Identification of Natural RORγt Ligands that Regulate the Development of Lymphoid Cells.” Cell Metab. 2015, 21, 286-297.
9. Ding, H.; Douglass Jr., E.F.; et al. “Quantitative Assessment of protein activity in orphan tissue and single cells using the metaVIPER algorithm.” Nature Comm. 2018, 9, 1471.
10. Douglass Jr, E.F.; Vasciaveo, A.; Alvarez, M., Realubit, R.; Karan, C.; Califano, A. “PANGEA: a drug perturbation RNAseq database for clinical oncology”, in prep.

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