Joshua R. Laber

Office: CPE 5.402

Emailjoshua.laber@utexas.edu

Linkedin: Joshua Laber

 

Howard A. Halff Endowed Graduate Fellowship in Chemical Engineering, 2011

Thrust 2000 Graduate Fellowship in Engineering, 2011-2014

Larry Holmes - South Texas Section, Society of Plasitcs Engineers Endowed Presidential Scholarship in Chemical Engineering, 2016

Baxter Young Investigator Award, 2016            

Education:

     University of California, Berkeley

            B.S. in Chemical Engineering (2011)

      The University of Texas at Austin

            M.S.E. in Chemical Engineering (2013)

      The University of Texas at Austin

            Ph.D. in Chemical Engineering (expected fall 2016)

Mailing Address:

                        

The University of Texas at Austin

Cockrell School of Engineering

McKetta Department of Chemical Engineering

200 E Dean Keeton St. Stop C0400

Austin, Texas 78712-1589

Research Interests:

 

Protein-protein interactions and their downstream effects on protein stability, aggregation, and immune responses.

 

Motivation:

Monoclonal antibodies are a desirable class of biomolecule to use as pharmaceuticals because of their high specificity and ability to treat many different diseases. There are currently over 30 FDA licensed antibody-based therapeutics on the market and hundreds more in development. They are mainly delivered intravenously in a dilute solution in a hospital or clinical setting, with each dose taking at least 4-5 hours and most patients requiring a dose every two weeks. It would be more convenient and cost-effective for the patient if a dose could be delivered subcutaneously at the patient's home, however as the concentration of protein is increased in solution the viscosity increases exponentially.

J. Liu, Steve Shire et. al. J. Pharm. Sci. 94 (2005) 1928-1940.

 

The major problem with high concentration protein solutions are that protein-protein interactions such as electrostatic interactions, hydrophobic interactions, hydrogen bonds, and van der Waals interactions occur between molecules which can cause aggregates and partially or fully unfold the protein. These problems cause the increase in viscosity of a protein solution, preventing the solution to be easily syringeable and causing the protein to lose its native structure and therapeutic function as well as can cause the body to elicit an immune response.

 

Our Research:

We are interested in how protein-protein interactions, such as electrostatic interactions on the surface of proteins, affects protein stability and aggregation. In particular, my project involves:

  • Investigation into how protein surface charge impacts solution properties by looking at panel of related supercharged proteins that we have shown we are able to form solutions at high concentrations (>250 mg/ml) which do not aggregate and maintain activity when >100-fold diluted.

  • Investigation of how the thermal and colloidal stability of several mAb candidates is related to CDR residues.

  • Characterization of the immune system during an anti-drug antibody response.

Publications:

 

​​Laber, JR, Dear BR, Martins ML, Jackson DE, DiVenere AM, Gollihar J, Ellington AE, Truskett TM, Johnston KP, and Maynard JA. Charge shielding prevents aggregation of supercharged GFP variants at high protein concentration.  Molecular Pharmaceutics 14 (10): 3269-3280 (2017).

Nguyen A.W., Wagner E.K., Laber J.R., Goodfield L.L., Smallridge W.E., Harvill E.T., Papin J.T., Wolf R.F., Padlan E.A., Bristol A., Kaleko M., Maynard J.A. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Science Translational Medicine, 2015.

Borwankar A.U., Dinin A.K., Laber J.R., Twu A., Wilson B.K., Maynard J.A., Truskett T.M., Johnston K.P. Tunable equilibrium nanocluster dispersions at high protein concentrations. Soft Matter, 2013.

...and several more in preparation.

© 2016 by The University of Texas at Austin. All rights reserved. Proudly created with Wix.com by Liz Prigge Wilkes

  • Facebook Social Icon
  • Twitter Social Icon
  • Google+ Social Icon