Antibodies are large, complex proteins used by the immune system to recognize and neutralize foreign invaders ranging from bacteria to viruses. The high binding affinity, exquisite binding specificity and low immunogenicity of human antibodies makes them attractive therapeutic agents for treating diverse disorders ranging from Parkinson’s disease to cancer. Nevertheless, there are several key unmet challenges in identifying, engineering, producing and formulating antibodies that are the focus of our research program.

The binding specificity and affinity of antibodies is governed by the sequence and conformation of their solvent-exposed peptide loops known as the complementarity-determining regions (CDRs). It has proven extremely challenging to design CDRs in a rational manner to mediate specific and high affinity antibody binding. We have discovered that the loops of small antibodies can be designed to recognize aggregated proteins linked to Alzheimer’s and related diseases by mimicking the process of protein aggregation (see Section I of our research page for more detail).

Antibodies have attracted much interest for preventing toxic protein aggregation linked to disorders ranging from Parkinson’s disease to infectious prion diseases. Nevertheless, antibodies are generally poor (low potency) inhibitors of protein aggregation because near-stoichiometric antibody concentrations are required to arrest aggregation. We are developing methods of designing antibodies that potently inhibit amyloid formation linked to multiple human disorders (Alzheimer’s disease, Parkinson’s disease and type 2 diabetes; see Section II of our research page for more detail).

Antibodies commonly use hydrophobic residues in their CDRs to mediate high affinity binding, yet these solvent-exposed hydrophobic residues can also lead to poor antibody solubility. We have developed a novel mutational approach for engineering CDR loops that dramatically increases antibody solubility without reducing binding affinity (see Section III of research page for more detail). We have also sought to eliminate the need to re-engineer antibodies by improving the selection of highly soluble antibodies (early in antibody discovery) and formulation conditions (early in antibody development) that maximize antibody solubility. We have developed a novel high-throughput screening method (self-interaction nanoparticle spectroscopy, SINS) for identifying antibody mutants and/or solution conditions that minimize the propensity of antibodies to associate and aggregate (see Section IV of our research page for more detail).





Lab members

Open positions

Lab news:

Lab discovers how antibodies overcome key affinity/stability trade-offs during affinity maturation (Scientific Reports, Mar 2017) [link]

Tessier co-chairs the 7th International Conference on Biomolecular Engineering (Jan 2017) [link]

Tessier presents the keynote lecture at RPI’s Trustee Celebration of Faculty Achievement (Dec 2016) [link]

Lab receives NSF grant to develop new antibody design and evolution methods (Aug 2016) [link]

Lab discovers a novel method for preparing stable antibody-gold conjugates and demonstrates their use in high-throughput screening applications (Aug 2016) [link]

Tessier promoted to Full Professor (Jul 2016) [link]

Tessier awarded the 2016 Biochemical Engineering Journal Young Investigator Award (Jun 2016) [link]

Lab reports a high-throughput method for assessing complex biophysical properties of therapeutic antibodies (Apr 2016) [link]

Lab discovers (in collaboration with the McNay lab at UAlbany) that their designed Alzheimer’s antibodies improve hippocampal signaling in rat models of diet-induced obesity (Mar 2016) [link]

Lab reports improved methods for designing anti-amyloid antibodies (Nov 2015) [link]

Lab reports a novel method for co-evolving antibody affinity and stability (Sept 2015) [link]

Lab discovers that highly soluble monoclonal antibodies can be identified prior to purification using a nanoparticle-based assay (Sept 2015) [link]

Lab published a review on Advances in Antibody Design in Annual Reviews in Biomedical Engineering

(Aug 2015) [link]

Tessier selected to participate in the 2015 U.S. National Academy of Engineering’s Frontiers of Engineering Symposium

(July 2015) [link]

Lab reports a nanoparticle screening method for detecting antibody aggregation in serum (Feb 2015) [link]

Tessier awarded the 2015 Biochemical Technology Young Investigator Award from the American Chemical Society (Dec 2014) [link]

Tessier named one of 30 young scientists under the age of 40 to be honored at the World Economic Forum in Tianjin, China (Sept 2014) [WEF link] [RPI link]

Tessier appointed the Richard Baruch M.D. Career Development (Endowed) Chair in Engineering (June 2014) [link]

Tessier named Review Editor for Frontiers in Molecular Biosciences (May 2014)

Tessier lab members Lilia Rabia (PhD student) and Evan Day (undergraduate student) awarded NSF Graduate Fellowships (April 2014)

Tessier awarded a Humboldt fellowship to support his research at the Max Planck Institute for Biochemistry (Mar 2014)

Lab discovers unique solubiliizing activities of positively and negatively charged mutations within the binding loops of single-domain antibodies (Jan 2014) [link]

Joe Perchiacca and Shantanu Sule (graduate students in the Tessier lab) win the 2013 Peterson Awards from the American Chemical Society (Division of Biochemical Technology) for best oral (Joe) and poster (Shantanu) presentations (Dec 2013)

Lab awarded NIH R01 to develop methods for designing antibody fragments specific for amyloid proteins (Dec 2013)

Lab publishes a review article on aggregation-resistant antibodies in Trends in Biotechnology (Aug 2013) [link]

Lab publishes an insight article on amyloid toxicity inhibitors in eLife (July 2013) [link]

Tessier named
Assistant Editor of the Journal of Biological Chemistry (April 2013)

Mark Julian (graduate student in Tessier lab) awarded an NSF Graduate Fellowship  (March 2013)

Tessier wins Rensselaer's School of Engineering Teaching Excellence Award (March 2013)

Lab reports a high-throughput method for assaying antibody stability during antibody selection in Molecular Pharmaceutics (Feb 2013) [link]

Tessier granted early tenure and will be promoted to Associate Professor in July 2013 (Dec 2012)

Lab reports a new method for designing potent antibody inhibitors of amyloid formation in PNAS (Oct 2012) [link to PNAS] [link to news story]

Lab awarded grant from NY State to develop Alzheimer’s antibodies  (Sept 2012) [link]

Kathryn Tiller (graduate student in Tessier lab) awarded an NSF Graduate Fellowship  (Sept 2012)

Lab awarded an NSF grant to develop methods for designing conformation-specific antibodies (Sept 2012) [link]

Lab reports a novel approach for engineering aggregation-resistant domain antibodies in Protein Engineering, Design & Selection (June 2012) [link]

Tessier presents the Allan P. Colburn Memorial Lecture at the University of Delaware (May 2012) [link]

Lab discovers key structural features of toxic oligomers of the Alzheimer's beta-amyloid peptide (April 2012) [link]

Tessier wins Rensselaer's Early Career Award (April 2012) [link]

Tessier wins Rensselaer's School of Engineering Research Excellence Award (April 2012) [link]

Ali Reza Ladiwala (graduate student in Tessier lab) wins Rensselaer's Karen and Lester Gerhardt Prize in Science and Engineering (April 2012)

Lab discovers that polyphenolic disaccharides are unusually effective at preventing protein aggregation (February 2012) [link]

Lab reports a motif-grafting strategy for designing conformation-specific antibodies against beta-amyloid oligomers and fibrils in PNAS (October 2011) [link to PNAS] [link to news story]

Lab reports a high-throughput, nanoparticle-based screening method for measuring monoclonal antibody self-association in Biophysical Journal (August 2011) [link]

Lab identifies structural mechanisms used by infectious prions to cross species barriers (August 2011) [link]

Lab discovers that aromatic compounds conjugated with sugars potently disaggregate toxic oligomers of beta-amyloid associated with Alzheimer's disease (June 2011) [link]

Lab identifies novel mutations that prevent antibody aggregation (May 2011) [link]

Lab awarded grant from the American Health Assistance Foundation to investigate structural differences between toxic and non-toxic oligomers of beta-amyloid associated with Alzheimer's disease (March 2011) [link]

Genetic Engineering News featured high-throughput protein self-interaction research in Tessier lab (February 2011) [link]

Lab reports three pathways used by aromatic small molecules to selectively remodel toxic soluble oligomers and fibrils of beta-amyloid in the Journal of Biological Chemistry (November 2010) [link]

Tessier wins Pew Scholars Award in Biomedical Sciences (June 2010) [link]

Lab reports that resveratrol selectively remodels toxic soluble oligomers and fibrils of beta-amyloid in the Journal of Biological Chemistry (May 2010) [link]

Tessier wins NSF CAREER Award (March 2010) [link]

Tessier & Lindquist publish a review in Nature Structural & Molecular Biology on prion structure, conformational variants and species barriers (June 2009) [link]

Lab publishes new approach for measuring weak protein interactions in Biotechnology & Bioengineering (June 2009) [link]

Lab awarded NIH grant to study the structural basis of species-specific infectivities of prion strain variants (May 2009)

Tessier awarded Alzheimer’s Association New Investigator Research Grant (July 2008) [link]

Lab publishes JACS paper on self-interaction nanoparticle spectroscopy (Feb 2008) [link]