Faculty Profile

Dr. Jonathan R. Lai, Ph.D.

Jonathan R. Lai, Ph.D.

Professor, Department of Biochemistry

Professional Interests


Peptide and protein chemistry

Our group is broadly interested in the application of peptide, protein and antibody engineering methods for the discovery and development of novel immunotherapies and vaccines. Projects are highly interdisciplinary and involve aspects such as phage display, structure-based protein design, bispecific antibody engineering, structural biology, virology, and cancer biology. Current direction include:

1.     Engineered antibodies as virus immunotherapies. The use of monoclonal antibodies (mAbs) as therapeutics (immunotherapy) has been highly successful for oncology and other indications, but application of mAbs to viral immunotherapy is only now emerging. mAbs offer an advantage of being highly specific, with little adverse effects. Furthermore, mAbs can engage in Fc-related functions that may serve to promote clearance of infections. We have been using state-of-the-art protein engineering methods to identify, characterize, and evaluate novel virus immunotherapies against Ebola virus, Dengue virus, and Chikungunya virus. We focus on developing new therapeutics by protein engineering that may have features that are not possible with conventional (natural) antibodies.

2.     Immunogen design for flavivirus vaccine discovery. Dengue virus is a mosquito-transmitted flavivirus that causes hundreds of millions of human infections world-wide each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions.  Dengue virus vaccine design has been complicated by the recent emergence of Zika virus (ZIKV), another flavivirus. We have been using structure-guided protein engineering to develop novel immunogens that elicit DENV and ZIKV protective antibody responses.  Our strategy focuses on common susceptible epitopes that may be structurally engineered.

3.     Dissection and engineering of protein-protein and protein-antibody interactions by phage display.  Phage display is a combinatorial technique that permits the selection of binding clones from highly diverse protein libraries.  We have used phage display to dissect critical determinants underlying specific protein-protein and protein-antibody interactions. Ultimately, this information can be utilized to design new proteins or antibodies with enhanced function; and contributes generally to our knowledge of protein recognition.  Projects focus on applications in T-cell immunology, chronic lymphocytic leukemia, and viral vaccine design.


Selected Publications

 Selected Recent Publications

Frei, J. C.; Wirchnianski, A. S.;Govero, J.; Vergnolle,O;Dowd, K. A.; Pierson, T. C.; Kielian, M; Girvin M. E.; Diamond, M. S.; Lai, J. R.* Engineered Dengue Virus Domain III Proteins Elicit Cross-Neutralizing Antibody Response in Mice. J.Virol. In press.

Nyakatura, E. K., Zak, S. E., Wec, A. Z., Hofmann, D., Shulenin, S., Bakken, R. R., Aman, M. J., Chandran, K., Dye, J. M., Lai, J. R.* Design and Evaluation of Bi- and Trispecific Antibodies Targeting Multiple Filovirus Glycoproteins. J. Biol. Chem. 2018293, 6201-6211. 

Lin, T.Y.; Lai, J. R.*Interrogation of Side Chain Biases for Oligomannose Recognition in Antibody 2G12 via Structure-Guided Phage Display Libraries. Bioorg. Med. Chem, 2017, 25, 5790-5798.

Hofmann, D. H.; Zak, S. E.; Nyakatura, E. K.; Mittler, E.; Bakken, R. R.; Chandran, K.; Dye, J. M.; Lai, J. R.*Mechanistic and Fc Requirements for Inhibition of Sudan Virus Entry and In Vivo Protection by a Synthetic Antibody.  Immunol. Lett.2017190, 289-295.

Wec, A. Z.; Herbert, A. S.; Murin, C. D.; Nyakatura, E. K.; Abelson, D. M.; Fels, J. M.; He, S.; James, R. M.; de La Vega, M. A.; Zhu, W.; Bakken, R. R.; Goodwin, E.; Turner, H. L.; Jangra, R. K.; Zeitlin, L.; Qiu, X.; Lai, J. R.; Walker, L. M.; Ward, A. B.; Dye, J. M.*; Chandran, K.*; Bornholdt, Z. A.* Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses. Cell, 2017, 169, 878-890.

Nyakatura, E. K.; Soare, A. Y.; Lai, J. R.* Bispecific Antibodies for Viral Immunotherapy. Hum. Vaccin. Immunother., 2017, 13, 836-842.

Wec,  A.Z.; Nyakatura, E. K.; Herbert, A. S.; Howell, K. A.; Holtsberg, F. W.; Bakken, R. R.; Mittler, E.; Christin, J. R.; Shulenin, S.; Jangra, R. K.; Bharrhan, S.; Kuehne, A. I.; Bornholdt, Z. A.; Flyak, A. I.; Saphire, E. O.; Crowe, J. E. Jr*, Aman, M. J.*, Dye, J. M.*, Lai, J. R.*, Chandran K.* A "Trojan horse" bispecific antibody strategy for broad protection against ebolaviruses. Science, 2016, 354, 350-354.

Frei, J. C.; Lai, J. R.* Protein and Antibody Engineering by Phage Display. Methods Enzymol., 2016, 580, 45-87.

Frei, J. C.; Nyakatura, E. K.; Zak, S. E.; Bakken, R. A.; Chandran, K.; Dye, J. M.*; Lai, J. R.*  Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses.  Sci. Rep., 2016, 6, 19193.

Uchime, O.; Dai, Z.; Biris, N.; Lee, D.; Sidhu, S. S.; Li, S.; Lai, J. R.*; Gavathiotis, E.* Synthetic Antibodies Inhibit Bcl-2-associated X Protein (BAX) through Blockade of the N-terminal Activation Site.  J. Biol. Chem., 2016, 291, 89-102.

Frei, J. C.; Kielian, M.; Lai, J. R.* Comprehensive Mapping of Functional Epitopes on Dengue Virus Glycoprotein E DIII for Binding to Broadly Neutralizing Antibodies 4E11 and 4E5A by Phage Display. Virology, 2015, 485, 371-382.

Liu, Y.; Higgins, C. D.; Overstreet, C. M.; Rai, K. R.; Chiorazzi, N.*; Lai, J. R.*   Peptides that Bind Specifically to an Antibody form a Chronic Lymphocytic Leukemia Clone Expressing Unmutated Immunoglobulin Variable Region Genes.  Mol. Med., 2013, 19, 245-252.

More Information About Dr. Jonathan Lai

Lai Group Webpage

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Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 519
Bronx, NY 10461

Tel: 718.678.1024

Research Information

In the News

Science News quotes Dr. Jonathan Lai on phage display, a molecule-manufacturing technique he uses to develop vaccines. The creators of phage display won the 2018 Nobel Prize in chemistry. 

Genetic Engineering & Biotechnology News interviews Dr. Jonathan Lai about new approaches to antibody engineering that could lead to novel drugs effective against various viruses, including Ebola.  

More media coverage