The Robinson Laboratory is interested in understanding the fundamental interactions between molecules, both in isolation and in the complex environment of the cell. We are investigating the determinants of protein folding and misfolding, and have developed several novel approaches to inhibit protein misfolding and aggregation. This has applications for “difficult-to-express” proteins such as membrane proteins, and for control of production of biotherapeutics, such as antibodies. We also study cellular interactions that lead to aggregation and transmission of pathogenic tau protein, which is relevant to Alzheimer’s disease, and several other neurodegenerative diseases including corticobasal degeneration.
Anne Skaja Robinson joined the faculty of Carnegie Mellon in November of 2018 as is the Department Head and Trustee Professor of Chemical Engineering. Prior to that, she was the Catherine and Henry Boh Professor in Engineering and Chair of Chemical and Biomolecular Engineering at Tulane University from 2012-2018. Robinson started her academic career at University of Delaware, where she rose through the ranks to become a full professor and associate department head. Her honors include a DuPont Young Professor Award, a National Science Foundation Presidential Early Career Award for Science and Engineering (PECASE) Award, and she is a fellow of the American Institute for Medical and Biological Engineering and the American Institute of Chemical Engineers. From 2015-2017, she served on the Board of Directors of the American Institute of Chemical Engineers. She is on the advisory board of Biotechnology and Bioengineering and the editorial board of Biotechnology Journal, and has been an ad hoc reviewer for many NIH and NSF study sections. She is also a member of the Advisory Committee for Pharmaceutical Sciences of the Food and Drug Administration.
Identifying and overcoming obstacles to GPCR expression and characterization
Human G-protein coupled receptors (GPCRs) represent the largest family of integral membrane receptors that are involved in intercellular communication in response to diverse external stimuli. GPCRs play a myriad number of physiological roles in humans, leading to a substantial pharmacological interest in modulating this signaling activity via novel pharmaceutically active molecules. Efforts to better understand GPCR ligand specificity, structure, stability, and assembly are hampered by the difficulties associated with producing these integral membrane proteins. Current projects in this area includes re-engineering of the GPCRs to improve correct folding for both cellular screening and production, and biophysical characterization of ligand-receptor and membrane-receptor interactions.
Understanding and controlling protein aggregation
Recombinant antibody therapy emerged in the 1990s as a versatile and effective means to treat patients afflicted with a wide variety of diseases. The market for these drugs is in the tens of billions of dollars per year and continues to expand as more drugs achieve FDA approval. One of the lab goals is to improve the industrial processes in order to ensure that biologics like antibodies are manufactured to be as efficient, potent, and inexpensive as possible. Current projects are to develop methods to improve on-line detection and control of production (including glycosylation) to reduce cost, and to examine antibodies under varied environmental conditions in order to model and predict characteristics like aggregation and stability (improve in vivo and in vitro half-lives).
Cellular mechanisms controlling protein quality and human disease
A protein called “tau,” found in healthy neuron cells, can form insoluble species called neurofibrillary tangles; these “tau tangles” are prominent features and hallmarks of several neurodegenerative diseases including Alzheimer’s Disease, corticobasal degeneration (CBD), and Parkinson’s Syndrome. Goals of the research effort in the Robinson laboratory are to understand the molecular and cellular processes that lead to these and other disease-related forms of tau, in order to identify the best targets for therapeutic intervention. Current projects in the lab include determining the role of different tau isoforms in fibril formation, identifying the mechanism(s) for cell-to-cell tau transmission, which may be physiological, pathological, or both, and determining methods to selectively inhibit pathological transmission.
Kirsten Swonger Koretz
Former lab members
Carnegie Mellon University
- Evan Wells, December,2020, Post-translational modifications to recombinant proteins: Roles in antibody production and protein aggregation, Janssen Pharmaceuticals
- Claire McGraw, April 2018, Role of Cholesterol in the Function of the G Protein Coupled Receptor Adenosine A2a Receptor Postdoc, Tulane University; Professor, Delgado Community College
- Kirsten Swonger Koretz, May 2019, Effects of the adenosine A2A receptor C-terminus on ligand binding, stability, and downstream signaling Postdoc, Carnegie Mellon University
- Abhinav Jain, September 2019, G Protein Coupled Receptor Expression and Signaling in Yeast: Design and Optimization of Host/Protein Platform for Therapeutic Development Upstream Process Development Scientist, IGM Biosciences
- Daniel Oseid, January 2020, Investigating the role of the membrane & cellular stress in neurodegenerative disorders MicroBio Consulting, Inc.
University of Delaware
- Brian Lefebvre, May 2002, High Pressure Dissociates Tailspike Aggregates and Promotes Native Structure Formation, Assistant Professor, Rowan University, NJ (2004-2008); Senior Fermentation Scientist, Cargill
- James Butz, June 2002, Characterizing and Optimizing GPCR Expression in Yeast, 2005-2006, Senior Scientist, Schering-Plough; 2006-2011, Associate Principal Scientist, Schering-Plough, NJ. Current position, Principal Scientist, Merck & Co.
- Brenda Danek, March 2003, Characterization of the Role of Disulfides in Folding of Tailspike Protein, J.D., 2008, NYU; current position: Associate, Intellectual Property Litigation, Latham & Watkins
- Jessica Sinacola, August 2003, Characterization and Reversal of the Aggregation of Single-Chain Antibodies, current position, Senior Principle Scientist, Sterile Process Technology & Engineering, Merck & Co, West Point, PA.
- Jason Smith, July 2003, Folding and Expression of Extremophilic Enzymes, 2003-2006 Postdoctoral Fellow, Carnegie Mellon University; 2006-2007, Product Development Engineer, Cohera Medical, Pittsburgh, PA; Manager of Research and Development at Carmell Therapeutics (2007-2018); current position: Assistant Teaching Professor and Associate Director of Partnerships, Carnegie Mellon University
- Ronald Niebauer, July 2005, Using GFP as a Sensor for Optimizing Expression of GPCRs, current position, Biotechnology Patent Examiner, US Patent Office, Washington, DC.
- June (Junghwa) Kim, June 2006, Roles of Folding Intermediate Conformation and Transient Disulfide Bonding on the Folding of P22 Tailspike Protein, current position, Senior Scientist, Bristol Myers Squibb/Celgene
- Sara Lawrence Powers, July 2006, Characterization and Expression of an Extremely Stable Hyperthermophilic Protein, 2006-2008, Postdoctoral Fellow, Wistar Institute; current position, R&D Scientist, Biomatrica
- Ping Xu, July 2006, Sensing and Analyzing the Unfolded Protein Response during Heterologous Protein Production, Cornell Weill Medical College (2007-2011); current position, Sr. Scientist I, Bristol Myers Squibb.
- Steven Bane, May 2007, Expression and Characterization of the Human Neurokinin 1 receptor from E. coli, Process Engineer, Sterile Process Technology & Engineering, Merck & Co, West Point, PA, 2007-2011; current position, Principal Scientist, Amgen
- Emily McCusker, December 2007, Overcoming Expression Obstacles in Producing Functional Components of the G-Protein Coupled Receptor Pathway, (2013-2017) Senior Medical Science Liason, Teva Pharmaceuticals; current position, Associate Director, Clinical Development at Allergan
- Michelle Spatara, May 2009, Protein folding and aggregation in vitro and in vivo, Postdoc UD (2010-2011); Manager, Novartis Vaccines (2011-2013); Investigator, Glaxo Smith Kline (2013-2018); current position: Principle Scientist, Takeda
- Michelle O’Malley, August 2009, Expression, Purification, and Biophysical Characterization of G-Protein Coupled Receptors Expressed from Saccharomyces cerevisiae, Postdoc Fellow, MIT (2009-2012); current position, Associate Professor, UC Santa Barbara
- Carissa Young, December 2012, Interrogation of Quality Control Mechanisms and Protein Trafficking in Saccharomyces cerevisiae, Postdoc, MIT (2012-2015) Senior Scientist, Applied Biomath (2015-2018); current position, Sr. Scientist, CMC Modeling, Cell Therapy, Takeda
- Zachary Britton, December 2012, Novel Approaches to the Expression and Purification of G Protein-coupled Receptors, current position, Scientist I, MedImmune
- Melissa St. Amand, September 2013, Toward Online Quality Control during Biopharmaceutical Production, Postdoc, NIH, NIDDK (2013-2015); current position, Senior Research Engineer, Schafer Corp.
- Andrea Naranjo, October 2014, Stability and Activity of a GPCR in vivo and in Membrane Mimetic Environments, current position, post-doctoral fellow, NIH
- Helen (Haixia Wu), September 2015, pH and Temperature-dependent Mechanisms of Non-Native Aggregation of Anti-CD40 IgG1 (co-advised, CJ Roberts, Univ Delaware), Scientist, Boehringer-Ingelheim
- Patrick McNeely, May 2016, Receptor-receptor, Ligand, and Membrane Interactions of the Adenosine A2A Receptor, Research Engineer, Apogee Research
- Ronald Maurer, July,2016, Biophysical Characterization of Folding and Aggregation Behavior in Model Single and Multi-Domain Proteins (co-advised, CJ Roberts, Univ Delaware), Senior Scientist, Process Development, Bristol-Myers Squibb Co.
- Devesh Radhakrishnan, October 2016, Modeling, Estimation, and Control of Glycosylation in Monoclonal Antibodies Produced in CHO Cells (co-advised, BA Ogunnaike, Univ Delaware), Senior Scientist I, Manufacturing Sciences Division, Biomarin
- Christopher O’Brien, December 2017, Colloidal Protein-Protein Interactions as a Design Target for Aggregation Resistance (co-advised with CJ Roberts, UD), Scientist II, Sanofi
Post-doctoral students supervised
- Matthew Gage, 2002-2005, Ph.D. 2001, Biochemistry, Purdue University, Present Position: Associate Professor of Chemistry, University of Massachusetts, Lowell
- David Raden, 2002-2009, Ph.D. 2000, Biochemistry, U. Mass. Medical School, current position, Assistant Professor, Department of Biological Sciences at University of Delaware
- Asokan Anbanandam, Feb-Aug 2007, Ph.D. 1999, Chemistry, Indian Institute of Technology, jointly advised by Prof. Tatyana Polenova, current position: Director, University of Kansas COBRE Biomolecular NMR Laboratory
- Özge Can, Feb 2009-May 2010, Ph.D. 2008, Cleveland State University, current position Associate Professor of Medical Biochemistry, Acibadem University School of Medicine, Istanbul, Turkey
- Hussain Dahodwala, 2012-2014, Ph.D. 2011, Chemical Engineering, Rensselaer Polytechnic Institute, Director of Upstream process Development, NIIMBL
- Arash Foroutan, 2013-2015, Ph.D. 2012, Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Spain, Current position, Postdoctoral Fellow, Northwestern
- Kory Blocker, 2014-2016, Ph.D. 2011, Department of Chemical Engineering, University of Delaware, current position, Associate Director, Upstream Process Development, Gene Therapy Program at University of Pennsylvania
- Claire McGraw, 2018, Ph.D. 2018, Department of Chemical and Biomolecular Engineering, Tulane University, Postdoc, Tulane University; Professor, Delgado Community College
- Liqing Song, 2019-present, Ph.D. 2018, Department of Chemical Engineering, Florida State University,
- Kirsten Swonger Koretz, 2019-present, Ph.D. 2019, Department of Chemical and Biomolecular Engineering, Tulane University
Robinson on remote education
ChemE Head Anne Robinson was quoted in Fortune discussing how teachers of different age groups are adapting to teaching in during the pandemic. “Students may be isolated from peers or in different time zones, so making sure they are doing OK mentally, physically, and intellectually is extremely vital,” said Robinson. “The regular social interaction of residential education is critical for graduate and postdoctoral students.”
Move to remote research invites innovation
While much of our lives can now function remotely, the transition to online poses unique challenges for academia—particularly for research universities like Carnegie Mellon.
Robinson named to National Academies study committee
ChemE department head Anne Skaja Robinson has been named to a National Academies of Sciences, Engineering, and Medicine committee of a new study, “Chemical Engineering in the 21st Century: Challenges and Opportunities,” that will analyze the status of the field.
Robinson named to National Academies study committee
Department Head Anne Skaja Robinson has been named to a committee of the National Academies of Sciences, Engineering, and Medicine’s Board on Chemical Science and Technology that will study the challenges and opportunities of chemical engineering in the 21st century.