Protein Engineering and Protein Therapeutics

Protein Engineering and Protein Therapeutics

Friday, September 9, 2016

The New York Academy of Sciences

Protein and antibody therapeutics ("biologics") have revolutionized modern medicine, allowing breakthroughs in treatment of cancer, cardiovascular disease, inflammation, and infectious disease. Recent advances in protein engineering methods have allowed access to novel therapeutic modalities, and provided capabilities to endow molecules with enhanced properties such as the ability to bind two or more targets simultaneously or to exhibit exquisite specificity towards particular post-translational modifications. This symposium will highlight state-of-the-art technologies in protein and antibody engineering, and antibody-drug conjugates. The implementation of these methods to specific diseases, or to develop unique research tools, will be discussed.

Registration Pricing

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Member (Student / Postdoc / Resident / Fellow)$0
Nonmember (Academia)$65
Nonmember (Corporate)$75
Nonmember (Non-profit)$65
Nonmember (Student / Postdoc / Resident / Fellow)$30

The keynote lecture by Dr. James A. Wells will be presented at no charge via Livestream, available during the event at: http://livestream.com/newyorkacademyofsciences/biologics2016

Agenda

* Presentation times are subject to change.


Friday, September 9, 2016

12:00 PM

Registration and Poster Set-up

12:30 PM

Welcome and Introduction
Caitlin McOmish, PhD, The New York Academy of Sciences

12:45 PM

Protein Engineering and Protein Therapeutics: Overview and Application to Viral Targets
Jonathan Lai, PhD, Albert Einstein College of Medicine

1:15 PM

Controlling Cell Signaling with Designer Binding Proteins
Shohei Koide, PhD, NYU Langone Medical Center

2:00 PM

Chemical Tagging and Customizing of Cellular Chromatin States Using Ultrafast Trans-splicing Inteins
Yael David, Department of Chemical Biology, Memorial Sloan Kettering Cancer Center

2:10 PM

A Structural Basis for Aza-Glycine Stabilization of Collagen
Alexander J. Kazsnel, University of Pennsylvania

2:20 PM

Coffee Break and Poster Judging

2:50 PM

Innovations in the Development of Next Generation Antibody Drug Conjugates (ADCs)
Manoj Charati, PhD, Pfizer

3:20 PM

Keynote Address:
Engineered Antibodies for RAS-Driven Surface Proteins
James A. Wells, PhD, University of California San Francisco
(available via Livestream)

4:05 PM

Closing Remarks and F1000Research Poster Prize
Jonathan Lai, PhD, Albert Einstein College of Medicine

4:10 PM

Poster Session and Networking Reception

5:10 PM

Adjourn

Organizers

Jonathan R. Lai, PhD

Albert Einstein College of Medicine

Sonya Dougal, PhD

The New York Academy of Sciences

Caitlin McOmish, PhD

The New York Academy of Sciences

Speakers

Yael David

MSKCC

Alexander J. Kasznel, BS

University of Pennsylvania

Shohei Koide, PhD

The Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center

Shohei Koide, PhD, is a Professor of Biochemistry and Molecular Pharmacology, and the Director of Cancer Biologics at the Perlmutter Cancer Center at NYU Langone Medical Center. He moved from the University of Chicago in Spring 2016, where he was a Professor of Biochemistry and Molecular Biology. He has been actively engaged in protein engineering and design over the last two decades. His research seamlessly integrates rational design, directed evolution, structural biology and cell biology to design highly functional but still simple protein molecules, and applies such synthetic proteins to biomedically important questions. He is a pioneer in the field of the so-called antibody mimics or alternative scaffolds. He invented the FN3 Monobody technology, the most widely adopted non-antibody scaffold system.

Jonathan R. Lai, PhD

Albert Einstein College of Medicine

Dr. Jonathan Lai is Associate Professor of Biochemistry at the Albert Einstein College of Medicine. He received his B.Sc (Hons.) in Biochemistry from Queen's University in Ontario, Canada, followed by his PhD is Chemistry and Biophysics at the University of Wisconsin–Madison where he worked with Prof. Sam Gellman on protein and peptide engineering. He was Helen Hay Whitney Post-Doctoral Fellow at Harvard Medical School from 2004–2007 in the groups of Prof. Chris Walsh and Prof. Stephen Harrison. Dr. Lai began his independent position at Einstein in 2007. His group has broad interests in protein engineering and has focused in recent years on application of these methods to discovery of new antiviral agents for Ebola, HIV-1, and Dengue viruses.

James A. Wells, PhD

University of California San Francisco

James A. Wells, PhD, has pioneered the engineering of proteins, antibodies, and small molecules that target catalytic, allosteric, and protein–protein interaction sites. He innovated mutagenesis methods including protein and substrate phage display, cassette mutagenesis, alanine-scanning, engineered enzymes for bioconjugations, and disulfide "tethering", a novel site-directed fragment based approach for drug discovery. These lead to important new insights into protease mechanisms and signaling pathways, growth factor signaling, hot-spots in protein–protein interfaces, and several protein engineered products sold by biotechnology companies today including Genentech, Genencor, and Pfizer. He received his PhD from Washington State University and Post-doc at Stanford University. Wells started his independent research career in Protein Engineering at Genentech (1982–1998), President and CSO at Sunesis Pharmaceuticals (1998–2005) and now Professor of Pharmaceutical Chemistry at UCSF. He has received societal awards from the American Chemical Society, the Protein Society, the American Peptide Society, and the ASBMB. He is an elected member of the National Academy of Sciences, American Academy of Arts and Sciences, and the National Academy of Inventors. He is an inventor on more than 60 patents, authored more than 170 peer-reviewed papers, and a founder of Sunesis, Calithera, and Warp Drive.

Manoj Charati, PhD

Pfizer

Manoj Charati, PhD, is a Principal Scientist in Oncology Research & Development at Pfizer. He joined Pfizer in 2010 and has over ten years' experience in drug delivery and protein/peptide chemistry. He currently oversees ADC bioconjugation, purification and analysis at Pfizer Oncology. Prior to joining Pfizer, he gained a PhD at the University of Delaware followed by a postdoctoral fellowship at University of Pennsylvania.

Sponsors

Presented by

  • The New York Academy of Sciences

Premiere Supporter

  • Pfizer

The Chemical Biology Discussion Group is proudly supported by the American Chemical Society and The Rockefeller University

This program is supported by an educational grant from AbbVie

Promotional Partners

The American Physiological Society

American Society for Pharmacology & Experimental Therapeutics (ASPET)

NewYorkBio

Society for Laboratory Automation and Screening

Abstracts

Innovations in the Development of Next Generation Antibody Drug Conjugates (ADCs)
Manoj Charati, PhD, Oncology Research & Development, Pfizer

Antibody Drug Conjugates (ADCs) represent a promising therapeutic modality for the treatment of cancer. This talk will describe technological advances in the development of efficacious and safer ADCs, including antibody engineering for delivery of novel cytotoxins. Recent improvements in conjugation chemistries and the impact of ADC biophysical properties on biological response will be highlighted.

Chemical Tagging and Customizing of Cellular Chromatin States Using Ultrafast Trans-splicing Inteins
Yael David, Department of Chemical Biology, MSKCC

Chromatin serves as the physiologically relevant form of eukaryotic genomes. Modifications to both the DNA and the histone-packaging proteins allow chromatin to act as a dynamic signaling platform to regulate genomic DNA access and ultimately establish and maintain cellular phenotypes, so-called epigenetic regulation. Aberrant chromatin signaling, as a consequence of abnormal inputs and outputs, is associated with many diseases, especially cancer. A full understanding of individual chromatin signaling processes, and their interconnectivity, is a prerequisite to the design of next-generation therapeutic agents that act to ameliorate epigenetic dysregulation. However, it is extremely challenging to explore specific epigenetic mechanisms in the complex milieu of the cell nucleus, and methods that bring the precision and flexibility of synthetic chemistry to a native chromatin context provide one possible solution to the problem. Here we present a synthetic biology method to engineer histones that bear site-specific modifications on cellular chromatin using protein trans-splicing.

A Structural Basis for Aza-Glycine Stabilization of Collagen
Alexander J. Kasznel, BS, University of Pennsylvania

Collagen is an essential protein in mammals, providing structure to skin, bones, cartilage, and the extracellular matrix. Native collagen is characterized by the variable amino acid sequence XYG. The variable X and Y positions in the XYG tripeptide are typically occupied by proline and hydroxyproline, respectively. Conversely, glycine is strictly conserved, and glycine mutations can propagate structural instability and collagen-related disease. This hallmark sequence promotes collagen’s self-assembly into a distinctive triple helical supramolecular structure. Previous studies in our lab have shown that the novel substitution of aza-glycine (azG) for glycine in synthetic CMPs can impart new hydrogen bonds to the triple helix, leading to unprecedented thermal stability and faster folding kinetics. In this study, we further explored this effect by performing an aza-glycine substitution on an alternative arginine-containing collagen sequence important for protein recognition: (POG)3-PRG-(POG)4 to (POG)3-PRazG-(POG)4. This single amino acid substitution substantially increased the thermal stability of the CMP (ΔTm = +8.6 °C), demonstrating the generality of aza-glycine as a stabilizing residue. The resulting azapeptide was crystallized and its structure was determined to 1.13 Å resolution using X-ray diffraction, providing a structural basis for collagen stabilization by aza-glycine. Overall, this study illustrates that aza-amino acid substitution is a synthetically accessible means of producing modular, hyperstable CMPs, even in applications where alternative peptide sequences are desired.
 
Coauthors: Yitao Zhang, PhD1, Yang Hai, PhD1, David M. Chenoweth, PhD1
1 University of Pennsylvania, Philadelphia, Pennsylvania, United States of America

Controlling Cell Signaling with Designer Binding Proteins
Shohei Koide, PhD, New York University Langone Medical Center

Signal transduction is mediated by complex protein interaction networks, and proteins involved in cell signaling are attractive targets for therapy. However, our ability to selectively control these proteins is still limited, and many proteins that play key roles in disease development and progression remain undruggable. Using designer binding protein platforms that combine structure-guided design and directed evolution, we have developed selective and potent inhibitors of diverse proteins. I will describe our current studies aimed at generating designer binding proteins that control key proteins in signaling, including RAS and oncogenic kinases, focusing on those exhibiting novel, allosteric modes of action.

Protein Engineering and Protein Therapeutics: Overview and Application to Viral Targets
Jonathan R. Lai, PhD, Albert Einstein College of Medicine

This seminar will provide a brief overview of protein therapeutics, recent developments in protein engineering approaches, and discuss specific implementation of these methods by our group to develop novel viral immunotherapeutics and vaccines.

Engineered Antibodies for Ras-driven Surface Proteins
James Wells, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California at San Francisco

How cell states change upon oncogene transformation, drug treatment, and differentiation is of fundamental interest to biology and biotechnology. The cell surface proteome (the "surfaceome") is critical to how cells interact with their outside environment and presents key targets for pharmaceutical intervention. Our group has been developing and applying new mass spectrometry technologies to understand how cell surfaces change during oncogene transformation and drug treatment. These data provide clues to the functional response the cell makes to oncogene cell rewiring. As importantly these data provide target lists for our industrialized pipeline for recombinant antibody generation to be used as orthogonal and more sensitive probes of these membrane proteins in a variety of cellular settings. Furthermore recombinant antibodies are tools for genetic manipulation and conjugation to probe function and essentiality. These antibodies are used in new multiplexed formats and therefore complement unbiased proteomics experiments but with greater sensitivity and through-put. I'll discuss these technologies and results as applied to understanding how RAS transformation leads to the cancer phenotype. Our studies reveal critical nodes and potential new cancer drug targets and biomarkers.

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The New York Academy of Sciences

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